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Introduction: Nanomaterials such as silver nanoparticles (AgNPs) have gained widespread application across various fields. However, the large-scale production and application of AgNPs have raised concerns about their distribution in the environment and potential pollution issues. Methods: This study investigates the toxic effects of AgNPs on the diatom Phaeodactylum tricornutum by employing electron microscopy for cellular observation, quantifying apoptotic cell numbers, and measuring antioxidant indicators. The research examines how varying concentrations of AgNPs induce stress in P. tricornutum and the specific mechanisms of the toxic effect. Results: The findings reveal that AgNPs induce apoptosis in P. tricornutum cells by triggering a mitochondria-mediated pathway, marked by a decrease in mitochondrial membrane potential and the activation of caspase enzymes. Additionally, AgNP exposure results in an overproduction of reactive oxygen species (ROS) within the algal cells, leading to lipid peroxidation of the cell membrane and a consequent increase in malondialdehyde (MDA) levels. This oxidative stress response induces the upregulation of antioxidant enzyme activities in an attempt to mitigate the excessive ROS. Discussion: ROS is identified as the primary factor responsible for inducing mitochondria-mediated apoptosis. The research results will provide a theoretical basis for understanding the toxic effects and mechanisms of AgNPs on marine microalgae. [ABSTRACT FROM AUTHOR]

Simple Summary: While the prognosis of hormone receptor-positive (HR+) breast cancer has been significantly improved, tamoxifen resistance remains a challenge in the treatment of HR+ breast cancer. This study identified that tRF-16-K8J7K1B, a novel small ncRNA derived from the 3′-end of tRNAAla-TGC, was highly expressed in tamoxifen-resistant cells compared to parental cells. Moreover, extracellular tRF-16-K8J7K1B confers tamoxifen resistance via incorporation into exosomes and then degrades the expression of apoptosis-related proteins, reducing the proportion of drug-induced cell apoptosis. Therefore, we propose that exosomal tRF-16-K8J7K1B could be a potential predictive biomarker and therapeutic target for overcoming tamoxifen resistance. Tamoxifen resistance remains a challenge in hormone receptor-positive (HR+) breast cancer. Recent evidence suggests that transfer ribonucleic acid (tRNA)-derived fragments play pivotal roles in the occurrence and development of various tumors. However, the relationship between tRNA-derived fragments and tamoxifen resistance remains unclear. In this study, we found that the expression of tRF-16-K8J7K1B was upregulated in tamoxifen-resistant cells in comparison with tamoxifen-sensitive cells. Higher levels of tRF-16-K8J7K1B were associated with shorter disease-free survival in HR+ breast cancer. Overexpression of tRF-16-K8J7K1B promotes tamoxifen resistance. Moreover, extracellular tRF-16-K8J7K1B could be packaged into exosomes and could disseminate tamoxifen resistance to recipient cells. Mechanistically, exosomal tRF-16-K8J7K1B downregulates the expression of apoptosis-related proteins, such as caspase 3 and poly (ADP-ribose) polymerase, by targeting tumor necrosis factor-related apoptosis-inducing ligand in receptor cells, thereby reducing drug-induced cell apoptosis. Therapeutically, the inhibition of exosomal tRF-16-K8J7K1B increases the sensitivity of breast cancer cells to tamoxifen in vivo. These data demonstrate that exosomal tRF-16-K8J7K1B may be a novel therapeutic target to overcome tamoxifen resistance in HR+ breast cancer. [ABSTRACT FROM AUTHOR]

Cyanobacterial blooms, usually dominated by Microcystis aeruginosa , pose a serious threat to global freshwater ecosystems owing to their production and release of various harmful secondary metabolites. Detection of the chemicals in M. aeruginosa exudates using metabolomics technology revealed that phytosphingosine (PHS) was one of the most abundant compounds. However, its specific toxicological mechanism remained unclear. CNE-2 cells were selected to illustrate the cytotoxic mechanism of PHS, and it was determined to cause excessive production of reactive oxygen species and subsequently damage the mitochondrial structure. Mitochondrial membrane rupture led to matrix mitochondrial membrane potential disintegration, which induced Ca2+ overload and interrupted ATP synthesis. Furthermore, rupture of the mitochondrial membrane induced the opening of the permeability transition pore, which caused the release of proapoptotic factors into the cytoplasm and the expression of apoptosis-related proteins Bax, Bcl-2, cytochrome-c and cleaved caspase-3 in CNE-2 cells. These events, in turn, activated the mitochondrially mediated intrinsic apoptotic pathway. A mitochondrial repair mechanism, namely, PINK1/Parkin-mediated mitophagy, was then blocked, which further promoted apoptosis. Our findings suggest that more attention should be paid to the ecotoxicity of PHS, which is already listed as a contaminant of emerging concern. [Display omitted] [ABSTRACT FROM AUTHOR]

In the present study, a fas apoptotic inhibitory molecule (FAIM) was identified from Ruditapes philippinarum (designated as RpFAIM). Multiple alignments and phylogenetic analysis strongly suggested that RpFAIM was a new member of the FAIMs family. The RpFAIM transcripts were constitutively expressed in a wide range of tissues, and dominantly expressed in hemocytes. After V. anguillarum or M. luteus challenge, the expression level of RpFAIM transcripts was significantly induced and reached the maximum level at 6 h and 24 h, respectively. Knockdown of RpFAIM down-regulated the transcript levels of NF-κB signaling genes (e.g. RpIKK, RpIκB, RpNF-κB). The results were roughly similar to those under bacterial stimulation. Moreover, RpFAIM primarily localized in the cell cytoplasm, and its over-expression inhibited the apoptosis of HeLa cells. These results revealed that RpFAIM perhaps regulated the NF-κB signaling pathways positively, which provided a better understanding of RpFAIM in innate immunity. • A fas apoptotic inhibitory molecule (FAIM) was first identified from the manila clam Ruditapes philippinarum. • The expression level of RpFAIM transcripts was significantly induced after challenged with V. anguillarum or M. luteus. • RpFAIM had a regulatory effect on NF-κB signaling pathways. • RpFAIM primarily localized in the cell cytoplasm and its over-expression inhibited the apoptosis. [ABSTRACT FROM AUTHOR]