Proteasome Dysfunction Leads to Suppression of the Hypoxic Response Pathway in Arabidopsis.

Proteasome is a large proteolytic complex that consists of a 20S core particle (20SP) and 19S regulatory particle (19SP) in eukaryotes. The proteasome degrades most cellular proteins, thereby controlling many key processes, including gene expression and protein quality control. Proteasome dysfunction in plants leads to abnormal development and reduced adaptability to environmental stresses. Previous studies have shown that proteasome dysfunction upregulates the gene expression of proteasome subunits, which is known as the proteasome bounce-back response. However, the proteasome bounce-back response cannot explain the damaging effect of proteasome dysfunction on plant growth and stress adaptation. To address this question, we focused on downregulated genes caused by proteasome dysfunction. We first confirmed that the 20SP subunit PBE is an essential proteasome subunit in Arabidopsis and that PBE1 mutation impaired the function of the proteasome. Transcriptome analyses showed that hypoxia-responsive genes were greatly enriched in the downregulated genes in pbe1 mutants. Furthermore, we found that the pbe1 mutant is hypersensitive to waterlogging stress, a typical hypoxic condition, and hypoxia-related developments are impaired in the pbe1 mutant. Meanwhile, the 19SP subunit rpn1a mutant seedlings are also hypersensitive to waterlogging stress. In summary, our results suggested that proteasome dysfunction downregulated the hypoxia-responsive pathway and impaired plant growth and adaptability to hypoxia stress.

Outcomes of Reoperation After Laparoscopic Gastric Plication Failure.

BACKGROUND: Management of failed laparoscopic gastric plication (LGP), defined as weight regain or inadequate weight loss, is a challenging issue. METHODS: This prospective investigation was conducted in individuals with morbid obesity who had undergone LGP from 2000 to 2016. Patients with weight loss failure, weight regain, and regain-prone cases were indicated for reoperation. Re-plication, laparoscopic one anastomosis gastric bypass (LOAGB), and modified jejunoileal bypass were done as revisional surgery. RESULTS: Revisional surgery was performed in 102 of 124 patients who needed reoperation. Overall, 39 re-plication, 38 LOAGB, and 25 malabsorptive procedures were performed. Re-plication was the shortest surgery and had the shortest length of hospital stay. The percentage of TWL at 6, 12, and 24 months of follow-up was 20.5%, 25%, and 26.8% for re-plication; 20.2%, 27%, and 30.5% for LOAGB; and 22.9%, 28.9%, and 32.6% for the malabsorptive procedure, respectively. In addition, the percentage of EWL at 6, 12, and 24 months of follow-up was 62%, 74.6%, and 79.6% for re-plication; 51.6%, 68.2%, and 75.9% for LOAGB; and 55.4%, 70.1%, and 79.1% for malabsorptive procedure, respectively. In long-term follow-up, according to %TWL, LOAGB and malabsorptive procedure had better outcome compared to re-plication, whereas there was no statistically significant difference in %EWL among the three surgical approaches. CONCLUSIONS: In terms of weight loss, reoperation on failed LGP was completely successful and no treatment failure was reported. All three revisional procedures, including re-plication, LOAGB, and malabsorptive procedure showed promising results and provided substantial weight loss. Since there is little information about the long-term efficacy and safety of revisional surgery on failed LGP, we highly recommend further investigations to confirm our results.