The nuclear receptor coactivator 4 regulates ferritinophagy induced by vibrio splendidus in coelomocytes of Apostichopus japonicus.

Iron homeostasis is vital for the host's defense against pathogenic invasion and the ferritinophagy is a crucial mechanism in maintaining intracellular iron homeostasis by facilitating the degradation and recycling of stored iron. The nuclear receptor coactivator 4 (NCOA4) serves as a ferritinophagy receptor, facilitating the binding and delivery of ferritin to the autophagosome and lysosome. However, NCOA4 of the sea cucumber Apostichopus japonicus (AjNCOA4) has not been reported until now. In this study, we identified and characterized AjNCOA4 in A. japonicus. This gene encodes a polypeptide containing 597 amino acids with an open reading frame of 1794 bp. The inferred amino acid sequence of AjNCOA4 comprises an ARA70 domain. Furthermore, a multiple sequence alignment demonstrated varying degrees of sequence homology between AjNCOA4 from A. japonicus and other NCOA4 orthologs. The phylogenetic tree of NCOA4 correlates with the established timeline of metazoan evolution. Expression analysis revealed that AjNCOA4 is expressed in all tested tissues, including the body wall, muscle, intestine, respiratory tree, and coelomocytes. Following challenge with Vibrio splendidus, the coelomocytes exhibited a significant increase in AjNCOA4 mRNA levels, peaking at 24 h. We successfully obtained recombinant AjNCOA4 protein through prokaryotic expression and prepared a specific polyclonal antibody. Immunofluorescence and co-immunoprecipitation experiments demonstrated an interaction between AjNCOA4 and AjFerritin in coelomocytes. RNA interference-mediated knockdown of AjNCOA4 expression resulted in elevated iron ion levels in coelomocytes. Bacterial stimulation enhanced ferritinophagy in coelomocytes, while knockdown of AjNCOA4 reduced the occurrence of ferritinophagy. These findings suggest that AjNCOA4 modulates ferritinophagy induced by V. splendidus in coelomocytes of A. japonicus.

The association between depression and metabolic syndrome and its components: a bidirectional two-sample Mendelian randomization study.

Observational studies suggested a bidirectional correlation between depression and metabolic syndrome (MetS) and its components. However, the causal associations between them remained unclear. We aimed to investigate whether genetically predicted depression is related to the risk of MetS and its components, and vice versa. We performed a bidirectional two-sample Mendelian randomization (MR) study using summary-level data from the most comprehensive genome-wide association studies (GWAS) of depression (n = 2,113,907), MetS (n = 291,107), waist circumference (n = 462,166), hypertension (n = 463,010) fasting blood glucose (FBG, n = 281,416), triglycerides (n = 441,016), high-density lipoprotein cholesterol (HDL-C, n = 403,943). The random-effects inverse-variance weighted (IVW) method was applied as the primary method. The results identified that genetically predicted depression was significantly positive associated with risk of MetS (OR: 1.224, 95% CI: 1.091-1.374, p = 5.58 × 10-4), waist circumference (OR: 1.083, 95% CI: 1.027-1.143, p = 0.003), hypertension (OR: 1.028, 95% CI: 1.016-1.039, p = 1.34 × 10-6) and triglycerides (OR: 1.111, 95% CI: 1.060-1.163, p = 9.35 × 10-6) while negative associated with HDL-C (OR: 0.932, 95% CI: 0.885-0.981, p = 0.007) but not FBG (OR: 1.010, 95% CI: 0.986-1.034, p = 1.34). No causal relationships were identified for MetS and its components on depression risk. The present MR analysis strength the evidence that depression is a risk factor for MetS and its components (waist circumference, hypertension, FBG, triglycerides, and HDL-C). Early diagnosis and prevention of depression are crucial in the management of MetS and its components.

Transcriptomic profiling of Alternaria longipes invasion in tobacco reveals pathogenesis regulated by AlHK1, a group III histidine kinase.

Tobacco brown spot, caused by Alternaria species, is a devastating tobacco disease. To explore the role of a group III histidine kinase (AlHK1) on A. longipes pathogenesis, the invasion progress of A. longipes was monitored. We found that the wild-type strain C-00 invaded faster than the AlHK1-disrupted strain HK∆4 in the early and middle infection stages and the reverse trend occurred in the late infection stage. Then, eight invasion transcriptomes were performed using RNA-Seq and 205 shared, 505 C-00 and 222 HK∆4 specific differentially expressed genes (DEGs) were identified. The annotation results showed seven antioxidant activity genes were specifically identified in the HKΔ4 DEGs. A subsequent experiment confirmed that HKΔ4 was more resistant to low concentrations oxidative stress than C-00. In addition, the results from 1) statistics for the number of DEGs, GO enriched terms, DEGs in clusters with rising trends, and 2) analyses of the expression patterns of some DEGs relevant for osmoadaptation and virulence showed that changes in C-00 infection existed mainly in the early and middle stages, while HKΔ4 infection arose mainly in the late stage. Our results reveal firstly the pathogenesis of A. longipes regulated by AlHK1 and provide useful insights into the fungal-plant interactions.

Levels and patterns of polybrominated diphenyl ethers in children's plasma from Dalian, China.

Polybrominated diphenyl ethers (PBDEs) are potential persistent organic pollutants which have raised many concerns in recent years. Research focusing on children exposure to PBDEs is important but insufficient. The levels and patterns of PBDEs in children's plasma from Dalian, China were studied for the first time. Seventeen PBDE congeners (BDE-30, 28, 35, 37, 75, 47, 66, 100, 99, 116, 155, 154, 153, 183, 181, 190 and 209) in 29 plasma samples were measured. Median PBDE concentration was 31.61 ng g(-1) lipid. BDE-153 was the dominant congener, followed by BDE-99, 47, and 183. High abundance of BDE-183 suggested a higher Octa-BDE use in China. No significant differences were observed between males and females or among different age groups. The levels of PBDEs in children's plasma in the present study were 9-30 times higher than those in non-occupational exposure people from Guangzhou, South China and those in human milk of general adults from other cities of China, but were at the moderate levels of those in children around the world. These results indicate that children in Dalian are at a high risk of exposure to PBDEs.