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Tuberous sclerosis complex (TSC), an inherited neurocutaneous disease, is caused by mutations in either the TSC1 or TSC2 gene. This genetic disorder is characterized by the growth of benign tumors in the brain, kidneys, and other organs. As a member of the orphan nuclear receptor family, nuclear receptor related 1 (Nurr1) plays a vital role in some neuropathological diseases and several types of benign or malignant tumors. Here, we explored the potential regulatory role of TSC1/2 signaling in Nurr1 and the effect of Nurr1 in TSC-related tumors. We found that Nurr1 expression was drastically decreased by the disruption of the TSC1/2 complex in Tsc2-null cells, genetically modified mouse models of TSC, cortical tubers of TSC patients, and kidney tumor tissue obtained from a TSC patient. Deficient TSC1/2 complex downregulated Nurr1 expression in an mTOR-dependent manner. Moreover, hyperactivation of mTOR reduced Nurr1 expression via suppression of autophagy. In addition, Nurr1 overexpression inhibited cell proliferation and suppressed cell cycle progression. Therefore, TSC/mTOR/autophagy/Nurr1 signaling is partially responsible for the tumorigenesis of TSC. Taken together, Nurr1 may be a novel therapeutic target for TSC-associated tumors, and Nurr1 agonists or reagents that induce Nurr1 expression may be used for the treatment of TSC. Key words: tuberous sclerosis complex, mechanistic target of rapamycin, Nurr1, autophagy, cell proliferation. La sclérose tubéreuse de Bourneville (STB), une maladie neurocutanée héréditaire, est causée par des mutations des genes TSC1 ou TSC2. Cette maladie génétique est caractérisée par la croissance de tumeurs bénignes dans le cerveau, les reins et d'autres organes. En tant que membre de la famille des récepteurs nucléaires orphelins, le récepteur Nurr1 joue un rôle essentiel dans certaines neuropathologies et plusieurs types de tumeurs bénignes ou malignes. Les auteurs ont exploré ici le rôle régulateur potentiel de la signalisation TSC1/2 sur Nurr1 et l'effet subséquent de Nurr1 dans les tumeurs associées à la STB. Ils ont constaté que l'expression de Nurr1 était considérablement réduite par la perturbation du complexe TSC1/2 dans les cellules Tsc2-nulles, les modèles murins de STB génétiquement modifiés, les tubules corticaux de patients atteints de STB et le tissu tumoral rénal obtenu d'un patient atteint de STB. La déficience en complexe TSC1/2 régulait à la baisse l'expression de Nurr1 de manière dépendante de mTOR. De plus, l'hyperactivation de mTOR réduisait l'expression de Nurr1 par la suppression de l'autophagie. Par ailleurs, la surexpression de Nurr1 inhibait la prolifération cellulaire et supprimait la progression du cycle cellulaire. Par conséquent, la signalization TSC/mTOR/autophagie/Nurr1 était partiellement responsable de la tumorigenèse dans la STB. En somme, Nurr1 peut constituer une nouvelle cible thérapeutique pour les tumeurs associées à la STB, et un agoniste de Nurr1 ou des réactifs induisant l'expression de Nurr1 pourraient être utilisés dans le traitement de la STB. [Traduit par la Rédaction] Mots-clés : sclérose tubéreuse de Bourneville, cible de la rapamycine mTOR, Nurr1, autophagie, prolifération cellulaire., 1. Introduction Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder featured with a potential for the development of benign or non-neoplastic hamartomas in nearly every organ system, including [...]

The stem tips of Zizania latifolia at different development stages were used as research materials. The expression stability of nine candidate reference genes (ACT1, H2B, UBI, EF-1α, GAPDH, β-actin, 60S, SKIP and AQP) were evaluated using qRT-PCR. The data were analyzed with GeNorm and NormFinder software. Present results indicated that the expression of ACT1 was stable and that it could be used as the optimal reference gene for studying the development stage of gall formation. ACT1 was selected as the reference gene to verify the expression level of the correlative genes in the gall formation stage of Z. latifolia. Our results were consistent with the previous transcriptome sequencing results. This study revealed that ACT1 was the classic reference gene for the analysis of correlative genes in all of the gall development stages of Z. latifolia. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a lethal progressive disease with elusive molecular mechanisms and limited therapeutic options. Aberrant activation of fibroblasts is a central hallmark of lung fibrosis. Here, we report that Golgi membrane protein 1 (GOLM1, also known as GP73 or GOLPH2) was increased in the lungs of patients with pulmonary fibrosis and mice with bleomycin (BLM)–induced pulmonary fibrosis. Loss of GOLM1 inhibited proliferation, differentiation, and extracellular matrix deposition of fibroblasts, whereas overexpression of GOLM1 exerted the opposite effects. Similarly, worsening pulmonary fibrosis after BLM treatment was observed in GOLM1–knock-in mice, whereas BLM-treated Golm1-knockout mice exhibited alleviated pulmonary fibrosis and collagen deposition. Furthermore, we identified long noncoding RNA NEAT1 downstream of GOLM1 as a potential mediator of pulmonary fibrosis through increased GOLM1 expression. Depletion of NEAT1 inhibited fibroblast proliferation and extracellular matrix production and reversed the profibrotic effects of GOLM1 overexpression. Additionally, we identified KLF4 as a downstream mediator of GOLM1 signaling to NEAT1. Our findings suggest that GOLM1 plays a pivotal role in promoting pulmonary fibrosis through the GOLM1–KLF4–NEAT1 signaling axis. Targeting GOLM1 and its downstream pathways may represent a novel therapeutic strategy for treating pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Drought is one of the most serious stresses affecting rice growth. Drought stress causes accelerated senescence, reduced fertility, and subsequent reductions in crop yield. Eukaryotic translation elongation factor EF1A is an important multifunctional protein that plays an essential role in the translation of eukaryotic proteins. In this study, we localized and cloned the OsEF1A gene in rice (Oryza sativa) in order to clarify its role in drought tolerance and yield. Subcellular localization revealed that it was mainly localized to the cell membrane, cytoskeleton and nucleus. Compared with the wild-type, OsEF1A overexpressing transgenic plants had significantly more tillers and grains per plant, resulting in a significantly higher yield. Increases in the relative water content and proline content were also observed in the transgenic seedlings under drought stress, with a decrease in the malondialdehyde content, all of which are representative of drought tolerance. Taken together, these findings suggest that OsEF1A plays a positive regulatory role in rice nutritional development under drought stress. These findings will help support future studies aimed at improving yield and stress tolerance in rice at the molecular level, paving the way for a new green revolution. [ABSTRACT FROM AUTHOR]

China shale oil, which is preserved in lacustrine shale with strong heterogeneity and relatively low maturity, has been a research hotspot of unconventional resources. However, controlling factors of shale oil enrichment and resource potential evaluation restricted efficient exploration and development of lacustrine shale oil. On the basis of well logging data, TOC content, Rock-Eval pyrolysis values, thermal maturity, 100 oil saturation data, and pressure coefficient, the core observation, X-ray diffraction analysis, physical property analysis, scanning electron microscopy, CT scan, well logging interpretation, and volumetric genesis method depending on three-dimensional geological modeling were used to determine enrichment factors and evaluate the resource potential of Qingshankou Formation shale oil in the Southern Songliao Basin. Shale oil was mainly enriched in the semideep and deep lake shale of K2qn1, with the high capacity of hydrocarbon generation and favorable petrological and mineralogical characteristics, pore space characteristics, and physical properties in the low structural part of the Southern Songliao Basin. The three-dimensional geological resource model of Qingshankou Formation lacustrine shale oil was determined by the key parameters (Ro, TOC, and S 1 ) of shale oil in the favorable zone of the Southern Songliao Basin, northeast China. The geological resource of shale oil, which was calculated by two grid computing methods ( F 1 and F 2 ), was, respectively, 1.713 × 10 12 kg and 1.654 × 10 12 kg. The great shale oil resource indicates a promising future in the exploration and development of Qingshankou Formation shale oil of the Southern Songliao Basin. [ABSTRACT FROM AUTHOR]