MiR-223 enhances lipophagy by suppressing CTSB in microglia following lysolecithin-induced demyelination in mice.

BACKGROUND: Lipid droplet (LD)-laden microglia is a key pathological hallmark of multiple sclerosis. The recent discovery of this novel microglial subtype, lipid-droplet-accumulating microglia (LDAM), is notable for increased inflammatory factor secretion and diminished phagocytic capability. Lipophagy, the autophagy-mediated selective degradation of LDs, plays a critical role in this context. This study investigated the involvement of microRNAs (miRNAs) in lipophagy during demyelinating diseases, assessed their capacity to modulate LDAM subtypes, and elucidated the potential underlying mechanisms involved. METHODS: C57BL/6 mice were used for in vivo experiments. Two weeks post demyelination induction at cervical level 4 (C4), histological assessments and confocal imaging were performed to examine LD accumulation in microglia within the lesion site. Autophagic changes were observed using transmission electron microscopy. miRNA and mRNA multi-omics analyses identified differentially expressed miRNAs and mRNAs under demyelinating conditions and the related autophagy target genes. The role of miR-223 in lipophagy under these conditions was specifically explored. In vitro studies, including miR-223 upregulation in BV2 cells via lentiviral infection, validated the bioinformatics findings. Immunofluorescence staining was used to measure LD accumulation, autophagy levels, target gene expression, and inflammatory mediator levels to elucidate the mechanisms of action of miR-223 in LDAM. RESULTS: Oil Red O staining and confocal imaging revealed substantial LD accumulation in the demyelinated spinal cord. Transmission electron microscopy revealed increased numbers of autophagic vacuoles at the injury site. Multi-omics analysis revealed miR-223 as a crucial regulatory gene in lipophagy during demyelination. It was identified that cathepsin B (CTSB) targets miR-223 in autophagy to integrate miRNA, mRNA, and autophagy gene databases. In vitro, miR-223 upregulation suppressed CTSB expression in BV2 cells, augmented autophagy, alleviated LD accumulation, and decreased the expression of the inflammatory mediator IL-1ß. CONCLUSION: These findings indicate that miR-223 plays a pivotal role in lipophagy under demyelinating conditions. By inhibiting CTSB, miR-223 promotes selective LD degradation, thereby reducing the lipid burden and inflammatory phenotype in LDAM. This study broadens the understanding of the molecular mechanisms of lipophagy and proposes lipophagy induction as a potential therapeutic approach to mitigate inflammatory responses in demyelinating diseases.

Incidence, clinical features, and survival outcomes of primary malignant lacrimal gland tumors: A population-based analysis.

BACKGROUND: Studies on the epidemiological information and prognosis of primary malignant lacrimal gland tumors (MLGTs) are rare for its low occurrence. The goal of our research was to investigate the epidemiological characteristics and survival outcomes of patients with MLGTs. METHODS: Incidence and demographic information of patients with MLGTs were collected from the Surveillance, Epidemiology, and End Results (SEER) database. To identify independent prognostic factors for disease-specific survival (DSS) and overall survival (OS), univariate and multivariate Cox regression analysis were performed. RESULTS: The overall incidence of primary MLGTs from 1975 to 2020 was 0.413/1,000,000 (according to the 2000 American standard population), with a steadily increasing incidence over years. A total of 964 patients with primary MLGTs were diagnosed, with an average age of 59.3 years. Of these, 53.2% were aged ≥60 years, 57.4% were female, and 77.1% were whites. Multivariate Cox regression analysis demonstrated that year of diagnosis, age, sex, histological type, SEER stage, surgery, and chemotherapy were independent prognostic factors of DSS or OS. CONCLUSIONS: Although primary MLGT is rare, its incidence has steadily increased in the past 46 years, and surgery was related to a better prognosis.

Characterization of the complete plastid genome of fireweed, Epilobium angustifolium, Shaanxi, China.

In this article, we studied the complete chloroplast genome of Fireweed, Epilobium angustifolium, an essential herbaceous perennial species of the genus Epilobium (Onagraceae), we used Illumina sequencing platform to characterize its whole plastid genome sequence. The results showed that its whole plastid genome is a typical qudaripartite circular molecule with 161,199 bp in total length, which contains a large single-copy region of 89,076 bp, a small single-copy region of 17,321 bp, and two inverted repeat regions of 27,401 bp. We identified 130 genes, 85 protein-coding genes, 37 tRNA, and 8 rRNA genes within this genome. The GC content in the chloroplast genome, LSC region, SSC region, and IR region were 38.1, 36.3, 33.1, and 42.7%, respectively. Phylogenetic analysis indicated that this plant was placed as a sister to the congeneric Epilobium ulleungensis, the two species were clustered into a clade with high bootstrap support.

Preliminary report on Sichuan golden snub-nosed monkeys (Rhinopithecus roxellana roxellana) at Laohegou Nature Reserve, Sichuan, China.

Comparative studies of subspecies under different ecological environments offer insights into intraspecies evolutionary adaptive mechanisms. Golden snub-nosed monkeys (Rhinopithecus roxellana) include three subspecies in China classified mainly by their morphological variations: R. r. roxellana (Sichuan and Gansu province), R. r. qinlingensis (Shaanxi province) and R. r. hubeiensis (Hubei province). These three subspecies live in three isolated area with different environments. Past works focused on the last two subspecies, but little information of habitat and behaviors of the nominated subspecies (R. r. roxellana) is available to date. We conducted a two-year study on the diet, activity budget, home range and social organization of 4 herds of R. r. roxellana, based on a total of 106 days' observation in Laohegou (LHG) Nature Reserve, Sichuan province. By using scan sampling method, our results suggest that the R. r roxellana feeds predominantly on leaves (77.5%), and spends more time feeding (40.0%) and resting (27.0%) while compared to the other two subspecies. Kernel Density Estimation Method based on GPS technology confirms that R. r roxellana has relatively larger home ranges (49.1 km2). The unit size (8.3 ± 3.5 individuals) of R. r roxellana is also smaller. Therefore, it is possible that differences in food availability in relation to habitats have important impacts on the feeding strategy and social system of the golden snub-nosed monkey. These results provide data to further explore intraspecific adaptations of living primates.