Minocycline attenuates the bilirubin-induced developmental neurotoxicity through the regulation of innate immunity and oxidative stress in zebrafish embryos.

When liver or intestinal function is impaired, bilirubin accumulates in the body and leads to neonatal jaundice. However, the potential negative effects caused by excessive accumulation of bilirubin such as developmental immunotoxicity and neurotoxicity remain unclear. We used a zebrafish model to establish bilirubin-induced jaundice symptoms and evaluated the toxic effects of bilirubin in aquatic organisms. Firstly, our results suggested that bilirubin exposure markedly decreased the survival rate, induced the developmental toxicity and increased the yellow pigment deposited in the zebrafish tail. Meanwhile, the number of macrophages and neutrophils was substantially reduced in a concentration-dependent manner. Besides, the antioxidant enzyme activities were greatly elevated while the inflammatory genes were significantly decreased after bilirubin exposure. Secondly, transcriptome analysis identified 708 genes were differentially expressed after bilirubin exposure, which animal organ morphogenesis, chemical synaptic transmission, and MAPK / mTOR signaling pathways were significantly enriched. Thirdly, bilirubin exposure leads to a significant decrease in the motility of zebrafish, including a dose-dependent decrease in the travelled distance, movement time, and average velocity. Moreover, the innate immune genes and apoptosis-related genes such as TLR4, NF-κB p65, STAT3 and p53 were elevated at a concentration of 10 µg/mL of bilirubin. Finally, our results further revealed that the anti-inflammatory and neuroprotective minocycline could partially rescue the bilirubin-induced neurobehavioral disorders in zebrafish embryos. In conclusion, our study explored the bilirubin-induced immunotoxicity and neurotoxicity in aquatic organisms, which will provide a theoretical basis for the treatment of neonatal jaundice in clinical practice.

Probing Primordial Chirality with Galaxy Spins.

Chiral symmetry is maximally violated in weak interactions [1], and such microscopic asymmetries in the early Universe might leave observable imprints on astrophysical scales without violating the cosmological principle. In this Letter, we propose a helicity measurement to detect primordial chiral violation. We point out that observations of halo-galaxy angular momentum directions (spins), which are frozen in during the galaxy formation process, provide a fossil chiral observable. From the clustering mode of large scale structure of the Universe, we construct a spin mode in Lagrangian space and show in simulations that it is a good probe of halo-galaxy spins. In the standard model, a strong symmetric correlation between the left and right helical components of this spin mode and galaxy spins is expected. Measurements of these correlations will be sensitive to chiral breaking, providing a direct test of chiral symmetry breaking in the early Universe.

Intracellular Delivery of Micron-Sized Magnetic Particles through a Virus Infection Pathway.

Micron-sized magnetic particles (M-MPs) have low toxicity, strong magnetic signals, and long-term retention capability, which are significant advantages for their application in biomedical imaging. Unfortunately, M-MPs are only internalized by few cell types, such as macrophages and phagocytes, and because of this lack of active intracellular delivery, their applications are restricted. The emergence of self-assembled virus-like particles (VLPs) offers a viable approach to drive M-MPs into cells, although the specific mechanism has not been revealed. In this study, we investigated in detail the intracellular pathway of M-MPs mediated by VLPs using a fluorescence co-localization method. The results indicated that the intracellular movement of M-MPs was consistent with the virus infection pathway, specifically caveolae-dependent endocytosis, transportation through microtubules, and accumulation in the endoplasmic reticulum. This study provides experimental support for the active transport of M-MPs into other cell types, thereby further extending their applications.