Macrophage infiltration contributes to the instability of atherosclerotic plaques. In the present study, we investigated whether selective inhibition of PI3K/Akt/mTOR signaling pathway can enhance the stability of atherosclerotic plaques by activation of macrophage autophagy. In vitro study, selective inhibitors or siRNA of PI3K/Akt/mTOR pathways were used to treat the rabbit's peritoneal primary macrophage cells. Inflammation related cytokines secreted by macrophages were measured. Ultrastructure changes of macrophages were examined by transmission electron microscope. mRNA or protein expression levels of autophagy related gene Beclin 1, protein 1 light chain 3 II dots (LC3-II) or Atg5-Atg12 conjugation were assayed by quantitative RT-PCR or Western blot. In vivo study, vulnerable plaque models were established in 40 New Zealand White rabbits and then drugs or siRNA were given for 8 weeks to inhibit the PI3K/Akt/mTOR signaling pathway. Intravascular ultrasound (IVUS) was performed to observe the plaque imaging. The ultrastructure of the abdominal aortic atherosclerosis lesions were analyzed with histopathology. RT-PCR or Western blot methods were used to measure the expression levels of corresponding autophagy related molecules. We found that macrophage autophagy was induced in the presence of Akt inhibitor, mTOR inhibitor and mTOR-siRNA in vitro study, while PI3K inhibitor had the opposite role. In vivo study, we found that macrophage autophagy increased significantly and the rabbits had lower plaque rupture incidence, lower plaque burden and decreased vulnerability index in the inhibitors or siRNA treated groups. We made a conclusion that selective inhibition of the Akt/mTOR signal pathway can reduce macrophages and stabilize the vulnerable atherosclerotic plaques by promoting macrophage autophagy.
Manganese (Mn) is an essential element for plant growth due to its participation in a series of physiological and metabolic processes. Mn is also considered a heavy metal that causes phytotoxicity when present in excess, disrupting photosynthesis and enzyme activity in plants. Thus, Mn toxicity is a major constraint limiting plant growth and production, especially in acid soils. To cope with Mn toxicity, plants have evolved a wide range of adaptive strategies to improve their growth under this stress. Mn tolerance mechanisms include activation of the antioxidant system, regulation of Mn uptake and homeostasis, and compartmentalization of Mn into subcellular compartments (e.g., vacuoles, endoplasmic reticulum, Golgi apparatus, and cell walls). In this regard, numerous genes are involved in specific pathways controlling Mn detoxification. Here, we summarize the recent advances in the mechanisms of Mn toxicity tolerance in plants and highlight the roles of genes responsible for Mn uptake, translocation, and distribution, contributing to Mn detoxification. We hope this review will provide a comprehensive understanding of the adaptive strategies of plants to Mn toxicity through gene regulation, which will aid in breeding crop varieties with Mn tolerance via genetic improvement approaches, enhancing the yield and quality of crops.
Incredible accomplishments have been achieved in agricultural production in China, but many demanding challenges for ensuring food security and environmental sustainability remain. Field experiments were conducted from 2011–2013 at three different sites, including Honghu, Shayang, and Jingzhou in China, to determine the effects of fertilization on enhancing crop productivity and indigenous nutrient-supplying capacity (INuS) in a rice (Oryza sativa L.)-rapeseed (Brassica napus L.) rotation. Four mineral fertilizer treatments (NPK, NP, NK and PK) were applied in a randomized complete block design with three replicates. Crop yields were increased by 19–41% (rice) and 61–76% (rapeseed) during the two years of rice-rapeseed rotation under NPK fertilization compared to PK fertilization across the study sites. Yield responses to fertilization were ranked NPK > NP > NK > PK, illustrating that N deficiency was the most limiting condition in a rice-rapeseed rotation, followed by P and K deficiencies. The highest and lowest N, P and K accumulations were observed under NPK and PK fertilization, respectively. The INuS of the soil decreased to a significant extent and affected rice-rapeseed rotation productivity at each site under NP, NK, and PK fertilization when compared to NPK. Based on the study results, a balanced nutrient application using NPK fertilization is a key management strategy for enhancing rice-rapeseed productivity and environmental safety.
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