Analysis of the heterogeneity and complexity of murine extraorbital lacrimal gland via single-cell RNA sequencing.

PURPOSE: The lacrimal gland is essential for maintaining ocular surface health and avoiding external damage by secreting an aqueous layer of the tear film. However, a healthy lacrimal gland's inventory of cell types and heterogeneity remains understudied. METHODS: Here, 10X Genome-based single-cell RNA sequencing was used to generate an unbiased classification of cellular diversity in the extraorbital lacrimal gland (ELG) of C57BL/6J mice. From 43,850 high-quality cells, we produced an atlas of cell heterogeneity and defined cell types using classic marker genes. The possible functions of these cells were analyzed through bioinformatics analysis. Additionally, the CellChat was employed for a preliminary analysis of the cell-cell communication network in the ELG. RESULTS: Over 37 subclasses of cells were identified, including seven types of glandular epithelial cells, three types of fibroblasts, ten types of myeloid-derived immune cells, at least eleven types of lymphoid-derived immune cells, and five types of vascular-associated cell subsets. The cell-cell communication network analysis revealed that fibroblasts and immune cells play a pivotal role in the dense intercellular communication network within the mouse ELG. CONCLUSIONS: This study provides a comprehensive transcriptome atlas and related database of the mouse ELG.

Design and synthesis of cabotegravir derivatives bearing 1,2,3-triazole and evaluation of anti-liver cancer activity.

Based on the structure of the anti-HIV drug cabotegravir, we introduced 1,2,3-triazole groups with different substituents to obtain 19 cabotegravir derivatives and tested their activity against HepG2 cells. The proliferation of HepG2 cells was examined following treatment with derivatives. Most of the compounds demonstrated significant inhibitory effects, particularly compounds KJ-5 and KJ-12 with IC50 values of 4.29 ± 0.10 and 4.07 ± 0.09 µM, respectively. Furthermore, both compounds 5 and 12 significantly caused cell apoptosis, G2/M arrest, and DNA damage, and suppressed invasion and migration in a concentration-dependent manner. In addition, KJ-5 and KJ-12 could trigger apoptosis via the mitochondrial pathway by increasing the ratio of Bax/Bcl-2 and activating cleaved caspase-9, cleaved caspase-3, and cleaved PARP.

Effect of propionamide on the growth of Microcystis flos-aquae colonies and the underlying physiological mechanisms.

Reducing the formation and growth of Microcystis colonies is an important prerequisite for the effective prevention and treatment of cyanobacterial blooms. Microcystis flos-aquae colonies was selected to investigate the potential of propionamide for use in controlling cyanobacterial blooms. Propionamide, one of the major allelochemicals in the root exudates of E. crassipes, was tested using different concentrations (0, 0.2, 1, and 2mgL-1) and dosing methods (one-time addition, semi-continuous addition, and continuous addition) to assess its effect on the growth of M. flos-aquae colonies. The results showed that in the presence of different concentrations of propionamide, the growth of M. flos-aquae colonies followed a logistic growth model, with a higher degree of fit at lower propionamide concentrations. With the semi-continuous addition of 2mgL-1 propionamide, the growth of M. flos-aquae colonies was markedly inhibited; the relative inhibition ratio of algal cells reached >90% at day 7 of co-culture, and the colonial form gradually disintegrated, transforming mainly into unicellular and bicellular forms and small colonies (average diameter<50µm). Following the semi-continuous addition of 2mgL-1 propionamide, the exopolysaccharide content, the chlorophyll-a concentration, and the maximum photochemical efficiency of photosystem II (Fv/Fm) trended downward in M. flos-aquae colonies, whereas the relative expression of the microcystin (MC) biosynthetic genes, mcyA and mcyH, was upregulated overall. Importantly, the synthesis of intracellular microcystin-LR (MC-LR) was decreased after an initial increase, and the extracellular MC-LR concentration did not differ significantly from that in the control group (p>0.05). Moreover, an acute toxicity test showed that 2mgL-1 propionamide was generally non-toxic to Daphnia magna. In conclusion, appropriate use of propionamide could effectively control the expansion of M. flos-aquae colonies without potential risks to the ecological safety of aquatic environments; therefore, propionamide can actually be used to regulate cyanobacterial blooms in natural waters.