Nuclear Receptor Nur77 Facilitates Melanoma Cell Survival under Metabolic Stress by Protecting Fatty Acid Oxidation.

Fatty acid oxidation (FAO) is crucial for cells to overcome metabolic stress by providing ATP and NADPH. However, the mechanism by which FAO is regulated in tumors remains elusive. Here we show that Nur77 is required for the metabolic adaptation of melanoma cells by protecting FAO. Glucose deprivation activates ERK2 to phosphorylate and induce Nur77 translocation to the mitochondria, where Nur77 binds to TPß, a rate-limiting enzyme in FAO. Although TPß activity is normally inhibited by oxidation under glucose deprivation, the Nur77-TPß association results in Nur77 self-sacrifice to protect TPß from oxidation. FAO is therefore able to maintain NADPH and ATP levels and prevent ROS increase and cell death. The Nur77-TPß interaction further promotes melanoma metastasis by facilitating circulating melanoma cell survival. This study demonstrates a novel regulatory function of Nur77 with linkage of the FAO-NADPH-ROS pathway during metabolic stress, suggesting Nur77 as a potential therapeutic target in melanoma.

Blocking PPARγ interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression.

Nuclear receptor Nur77 participates in multiple metabolic regulations and plays paradoxical roles in tumorigeneses. Herein, we demonstrated that the knockout of Nur77 stimulated mammary tumor development in two mouse models, which would be reversed by a specific reexpression of Nur77 in mammary tissues. Mechanistically, Nur77 interacted and recruited corepressors, the SWI/SNF complex, to the promoters of CD36 and FABP4 to suppress their transcriptions, which hampered the fatty acid uptake, leading to the inhibition of cell proliferation. Peroxisome proliferator-activated receptor-γ (PPARγ) played an antagonistic role in this process through binding to Nur77 to facilitate ubiquitin ligase Trim13-mediated ubiquitination and degradation of Nur77. Cocrystallographic and functional analysis revealed that Csn-B, a Nur77-targeting compound, promoted the formation of Nur77 homodimer to prevent PPARγ binding by steric hindrance, thereby strengthening the Nur77's inhibitory role in breast cancer. Therefore, our study reveals a regulatory function of Nur77 in breast cancer via impeding fatty acid uptake.

Synthesis of unsymmetrical 2,2'-biindolyl derivatives by a Cu-catalyzed N-arylation/Pd-catalyzed direct arylation sequential process.

A one-pot synthesis of unsymmetrical 2,2'-biindolyl derivatives through a Cu-catalyzed N-arylation/Pd-catalyzed direct arylation sequence was described. The reaction involved easily prepared o-gem-dibromovinyl substrates, and the desired biindolyls were obtained in moderate to good yields.

[The suppression effect and mechanism of arbuscular mycorrhizal fungi against plant root rot.] / ä¸›æžèŒæ ¹çœŸèŒå¯¹æ¤ç‰©æ ¹è ç— çš„æŠ‘åˆ¶æ•ˆåº”åŠå ¶æœºåˆ¶.

Root rot is a serious soil-borne disease, with negative consequences on crop yield and quality. Arbuscular mycorrhizal (AM) fungi are a group of soil microorganisms, which play important physiological and ecological functions by establishing symbionts with plant roots. AM fungi could induce plant resistance against root rot by regulating physiological and biochemical processes. As a biological agent, AM fungi are used to antagonize soil-borne diseases such as root rot, which is a hotspot in the field of plant-microorganism interaction. We comprehensively reviewed the suppression effect of AM fungi on plant root rot, and the effect of AM fungi on root morphology of host plant, plant nutrition levels, as well as their role in competing with pathogens for ecological sites, activating plant defense systems, and regulating root exudates. Finally, we discussed the potential mechanism of AM fungi inhibiting root rot, as well as the practical problems in the efficient utilization of AM fungi were discussed, in order to provide the theoretical basis for the biological control protocol to antagonize root rot with AM fungi.

Copper-catalyzed cascade syntheses of 2H-benzo[b][1,4]thiazin-3(4H)-ones and quinoxalin-2(1H)-ones through capturing S and N atom respectively from AcSH and TsNH(2).

A copper-catalyzed cascade method has been developed to synthesize the 2H-benzo[b][1,4]thiazin-3(4H)-ones from 2-halo-N-(2-halophenyl)-acetamides 1 and AcSH via the S(N)2/deacetylation/coupling process, and to synthesize the quinoxalin-2(1H)-ones from 1 and TsNH(2) via the S(N)2/coupling/desulfonation process. The target products were obtained with diversity at three positions on their scaffolds.

Transcriptome Analysis Unravels Metabolic and Molecular Pathways Related to Fruit Sac Granulation in a Late-Ripening Navel Orange (Citrus sinensis Osbeck).

Lanelate navel orange (Citrus sinensis Osbeck) is a late-ripening citrus cultivar increasingly planted in China. The physiological disorder juice sac granulation often occurs in the fruit before harvest, but the physiological and molecular mechanisms underlying this disorder remain elusive. In this study, we found that fruit granulation of the late-ripening navel orange in the Three Gorges area is mainly caused by the low winter temperature in high altitude areas. Besides, dynamic changes of water content in the fruit after freezing were clarified. The granulation of fruit juice sacs resulted in increases in cell wall cellulose and decreases in soluble solid content, and the cells gradually became shrivelled and hollow. Meanwhile, the contents of pectin, cellulose, and lignin in juice sac increased with increasing degrees of fruit granulation. The activities of pectin methylesterase (PME) and the antioxidant enzymes peroxidase (POD), superoxide dismutase, and catalase increased, while those of polygalacturonase (PG) and cellulose (CL) decreased. Furthermore, a total of 903 differentially expressed genes were identified in the granulated fruit as compared with non-disordered fruit using RNA-sequencing, most of which were enriched in nine metabolic pathways, and qRT-PCR results suggested that the juice sac granulation is closely related to cell wall metabolism. In addition, the expression of PME involved in pectin decomposition was up-regulated, while that of PG was down-regulated. Phenylalanine ammonia lyase (PAL), cinnamol dehydrogenase (CAD), and POD related to lignin synthesis were up-regulated, while CL involved in cellulose decomposition was down-regulated. The expression patterns of these genes were in line with those observed in low-temperature treatment as revealed by qRT-PCR, further confirming that low winter temperature is associated with the fruit granulation of late-ripening citrus. Accordingly, low temperature would aggravate the granulation by affecting cell wall metabolism of late-ripening citrus fruit.

One-pot synthesis of pyrimido[1,6-a]indol-1(2H)-one derivatives by a nucleophilic addition/Cu-catalyzed N-arylation/Pd-catalyzed C-H activation sequential process.

A novel and convenient one-pot synthesis of pyrimido[1,6-a]indol-1(2H)-one derivatives through a nucleophilic addition/Cu-catalyzed N-arylation/Pd-catalyzed C-H activation sequential process is described. The reaction of easily prepared ortho-gem-dibromovinyl isocyanates with N-alkyl-anilines gave the desired indole derivatives in moderate to good yields.