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Older livers are more prone to hepatic ischaemia/reperfusion injury (HIRI), which severely limits their utilization in liver transplantation. The potential mechanism remains unclear. Here, we demonstrate older livers exhibit increased ferroptosis during HIRI. Inhibiting ferroptosis significantly attenuates older HIRI phenotypes. Mass spectrometry reveals that fat mass and obesity-associated gene (FTO) expression is downregulated in older livers, especially during HIRI. Overexpressing FTO improves older HIRI phenotypes by inhibiting ferroptosis. Mechanistically, acyl-CoA synthetase long chain family 4 (ACSL4) and transferrin receptor protein 1 (TFRC), two key positive contributors to ferroptosis, are FTO targets. For ameliorative effect, FTO requires the inhibition of Acsl4 and Tfrc mRNA stability in a m6A-dependent manner. Furthermore, we demonstrate nicotinamide mononucleotide can upregulate FTO demethylase activity, suppressing ferroptosis and decreasing older HIRI. Collectively, these findings reveal an FTO-ACSL4/TFRC regulatory pathway that contributes to the pathogenesis of older HIRI, providing insight into the clinical translation of strategies related to the demethylase activity of FTO to improve graft function after older donor liver transplantation. Transplanted older livers are prone to injury through unclear mechanisms, precluding effective treatment development. Here, the authors show that decreased FTO expression in older livers inhibits Acsl4 and Tfrc mRNA stability in an m6A-dependent manner, increasing cell death in older donor livers. [ABSTRACT FROM AUTHOR]

The cytokinin response regulator (RR) gene is essential for cytokinin signal transduction, which plays a crucial role in plant growth and development. Here, we applied bioinformatics to Rhododendron delavayi's genome to identify its RR gene family and systematically analyzed their gene characteristics, phylogenetic evolution, chromosomal localization, collinearity analysis, promoter cis-elements, and expression patterns. Overall, 33 RdRR genes were distinguished and classified into three types. All these genes harbored motif 5 (YEVTTVNSGLEALELLRENKB), the most conserved one, along with the plant-conserved domain (REC domain), and could be mapped to 10 chromosomes with four gene pairs of segmental replication events but no tandem replication events; 13 RdRR genes showed collinearity with Arabidopsis thaliana genes. Promoter analysis revealed multiple hormone-related cis-elements in the RR genes. After a TDZ (thidiazuron) treatment, 13 genes had higher expression levels than the control, whose magnitude of change depended on the developmental stage of leaves' adventitious buds. The expression levels of RdRR14, RdRR17, RdRR20, and RdRR24 agreed with the average number of adventitious buds post-TDZ treatment. We speculate that these four genes could figure prominently in bud regeneration from R. delavayi leaves in vitro. This study provides detailed knowledge of RdRRs for research on cytokinin signaling and RdRR functioning in R. delavayi. [ABSTRACT FROM AUTHOR]

High expression of suppressors of cytokine signalling (SOCS) has been detected during various viral infections. As a negative feedback regulator, SOCS participates in the regulation of multiple signalling pathways. In this study, to study the related mechanism between SOCS and BDV and to explore the effect of SOCS on IFN pathways in nerve cells, downregulated of SOCS1/3 in oligodendroglial (OL) cells and OL cells persistently infected with BDV (OL/BDV) were constructed with RNA interference technology. An interferon inducer (poly I:C, PIC) and an IFN‐α/β R1 antibody were used as stimulation in the SOCS1/3 low‐expression cell models, qRT‐PCR was used to detect type I IFN and BDV nucleic acid expression, Western blot was used to detect the expression of BDV P40 protein. After BDV acute infection with OL cells which with downregulated SOCS expression, the virus accounting was not detected, and the viral protein expression was lower than that of OL/BDV cells; the OL/BDV cells with downregulated SOCS expression had lower virus nucleic acid and protein expression than OL/BDV cells. Stimulated by IFN‐α/β R1 antibody, the expression of type I interferon in OL/BDV cells decreased, and the content of BDV nucleic acid and protein increased, which was higher than that of OL/BDV cells. From the results, it was concluded that downregulating SOCS1/3 can inhibit the formation of acute BDV infection and virus replication in persistent BDV infection by promoting the expression of IFN‐α/β and that SOCS can be used as a new target for antiviral therapy. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the association between methylation and the high expression of the suppressor of cytokine signaling 1 (SOCS1) in ovarian cancer by detecting the methylation rate and the degree of expression. The present study investigated the expression of SOCS1 mRNA and SOCS1 protein in ovarian cancer and normal ovary tissues using reverse transcription-quantitative polymerase chain reaction (PCR) and immunohistochemistry, and the methylation status of the CpG islands of SOCS1 mRNA in ovarian cancer tissue were examined using a methylation-specific PCR. The expression levels of SOCS1 mRNA in ovarian cancer specimens were significantly increased compared with that in the normal ovary tissues (P=0.0215). Consistent with this, the expression levels of SOCS1 protein in ovarian cancer specimens were significantly increased, while the methylation rate of SOCS1 mRNA was significantly decreased compared with that in the normal ovary tissues. Therefore, it may be concluded that the low methylation rate of SOCS1 mRNA in ovarian cancer increased the expression of SOCS1 mRNA, which may serve a role in the development of ovarian cancer. [ABSTRACT FROM AUTHOR]

Ginsenosides, which mainly exist in rhizomes and roots of Panax notoginseng (Burk) F. H. Chen, exhibit various physiological functions and medicinal values. However, the accumulation process of ginsenosides in the rhizome, epidermis, and xylem of the main root is unknown. Herein, the temporospatial distribution and mechanism of variation of ginsenosides in the underground parts of three-year-old P. notoginseng were investigated. The results showed that the accumulation of ginsenosides in rhizomes accelerated from May. In 12-month growth stages (except May), the content of ginsenosides in the xylem and epidermis were higher than that in the rhizome. However, the ginsenosides in rhizomes increased rapidly, whereas the ginsenosides in the main root decreased from May to July. The expression levels of genes encoding squalene epoxidase, dammarenediol synthase, and uridine diphosphate-dependent glycosyltransferase (UGTPg1) in rhizomes were increased in May, whereas genes encoding squalene synthase, protopanaxadiol synthase, protopanaxatriol synthase, UGTPg45, and UGTPg29 were expressed at considerably increased levels in June. Distinct expression levels of genes related to ginsenoside biosynthesis were the main reasons for the temporospatial fluctuation of ginsenoside accumulation in the two tissues. weighted gene co-expression network analysis demonstrated that many transcripts regulated ginsenoside accumulation in underground tissues. These results provide essential data for farmers and processors participating in P. notoginseng cultivation and utilisation. • The distribution and variation of ginsenosides in Panax notoginseng. • The accumulation mechanism of ginsenosides during key period was investigated. • The ginsenosides spatial-temporal distribution and mechanism was first revealed. • Providing essential data for 6 billion RMB market of P. notoginseng in China. [ABSTRACT FROM AUTHOR]