Ethylene-mediated nitric oxide depletion pre-adapts plants to hypoxia stress

Timely perception of adverse environmental changes is critical for survival. Dynamic changes in gases are important cues for plants to sense environmental perturbations, such as submergence. In Arabidopsis thaliana, changes in oxygen and nitric oxide (NO) control the stability of ERFVII transcription factors. ERFVII proteolysis is regulated by the N-degron pathway and mediates adaptation to flooding-induced hypoxia. However, how plants detect and transduce early submergence signals remains elusive. Here we show that plants can rapidly detect submergence through passive ethylene entrapment and use this signal to pre-adapt to impending hypoxia. Ethylene can enhance ERFVII stability prior to hypoxia by increasing the NO-scavenger PHYTOGLOBIN1. This ethylene-mediated NO depletion and consequent ERFVII accumulation pre-adapts plants to survive subsequent hypoxia. Our results reveal the biological link between three gaseous signals for the regulation of flooding survival and identifies key regulatory targets for early stress perception that could be pivotal for developing flood-tolerant crops

A covalently bound inhibitor triggers EZH2 degradation through CHIP‐mediated ubiquitination

Abstract Enhancer of zeste homolog 2 (EZH2) has been characterized as a critical oncogene and a promising drug target in human malignant tumors. The current EZH2 inhibitors strongly suppress the enhanced enzymatic function of mutant EZH2 in some lymphomas. However, the recent identification of a PRC2‐ and methyltransferase‐independent role of EZH2 indicates that a complete suppression of all oncogenic functions of EZH2 is needed. Here, we report a unique EZH2‐targeting strategy by identifying a gambogenic acid (GNA) derivative as a novel agent that specifically and covalently bound to Cys668 within the EZH2‐SET domain, triggering EZH2 degradation through COOH terminus of Hsp70‐interacting protein (CHIP)‐mediated ubiquitination. This class of inhibitors significantly suppressed H3K27Me3 and effectively reactivated polycomb repressor complex 2 (PRC2)‐silenced tumor suppressor genes. Moreover, the novel inhibitors significantly suppressed tumor growth in an EZH2‐dependent manner, and tumors bearing a non‐GNA‐interacting C668S‐EZH2 mutation exhibited resistance to the inhibitors. Together, our results identify the inhibition of the signaling pathway that governs GNA‐mediated destruction of EZH2 as a promising anti‐cancer strategy

Ethylene augments root hypoxia tolerance via growth cessation and reactive oxygen species amelioration

Flooded plants experience impaired gas diffusion underwater, leading to oxygen deprivation (hypoxia). The volatile plant hormone ethylene is rapidly trapped in submerged plant cells and is instrumental for enhanced hypoxia acclimation. However, the precise mechanisms underpinning ethylene-enhanced hypoxia survival remain unclear. We studied the effect of ethylene pre-treatment on hypoxia survival of Arabidopsis (Arabidopsis thaliana) primary root tips. Both hypoxia itself and re-oxygenation following hypoxia are highly damaging to root tip cells, and ethylene pre-treatments reduced this damage. Ethylene pre-treatment alone altered the abundance of transcripts and proteins involved in hypoxia responses, root growth, translation, and reactive oxygen species (ROS) homeostasis. Through imaging and manipulating ROS abundance in planta, we demonstrated that ethylene limited excessive ROS formation during hypoxia and subsequent re-oxygenation and improved oxidative stress survival in a PHYTOGLOBIN1-dependent manner. In addition, we showed that root growth cessation via ethylene and auxin occurred rapidly and that this quiescence behavior contributed to enhanced hypoxia tolerance. Collectively, our results show that the early flooding signal ethylene modulates a variety of processes that all contribute to hypoxia survival

Relationships between Hematopoiesis and Hepatogenesis in the Midtrimester Fetal Liver Characterized by Dynamic Transcriptomic and Proteomic Profiles

In fetal hematopoietic organs, the switch from hematopoiesis is hypothesized to be a critical time point for organogenesis, but it is not yet evidenced. The transient coexistence of hematopoiesis will be useful to understand the development of fetal liver (FL) around this time and its relationship to hematopoiesis. Here, the temporal and the comparative transcriptomic and proteomic profiles were observed during the critical time points corresponding to the initiation (E11.5), peak (E14.5), recession (E15.5), and disappearance (3 ddp) of mouse FL hematopoiesis. We found that E11.5-E14.5 corresponds to a FL hematopoietic expansion phase with distinct molecular features, including the expression of new transcription factors, many of which are novel KRAB (Kruppel-associated box)-containing zinc finger proteins. This time period is also characterized by extensive depression of some liver functions, especially catabolism/utilization, immune and defense, classical complement cascades, and intrinsic blood coagulation. Instead, the other liver functions increased, such as xenobiotic and sterol metabolism, synthesis of carbohydrate and glycan, the alternate and lectin complement cascades and extrinsic blood coagulation, and etc. Strikingly, all of the liver functions were significantly increased at E14.5-E15.5 and thereafter, and the depression of the key pathways attributes to build the hematopoietic microenvironment. These findings signal hematopoiesis emigration is the key to open the door of liver maturation

Ethylene-mediated hypoxia tolerance in Arabidopsis thaliana

Global warming has led to considerable changes in weather patterns over the past decades. Extreme climate events such as flooding, are expected to become even more frequent and severe in the future. Flooding being detrimental to major crop species, will have significant negative effects on global food production. Gas exchange rate is 104 times slower underwater than in the air. Consequently, plant growth underwater suffers from a lack of oxygen (O2) and carbon dioxide, which are essential for respiration and photosynthesis, respectively. The resulting reduction in photosynthesis and respiration lead to a carbohydrate and energy crisis ultimately affecting plant performance. Restricted gas diffusion underwater also results in rapid accumulation of the plant hormone ethylene in flooded plant tissues. Ethylene has been shown to be one of the key regulators of major flood adaptive responses. Unlike other flooding signals such as O2 and light availability that can be variable depending on other factors, ethylene accumulation under flooding conditions will always occur due to physical entrapment. Therefore, it is considered a consistent and reliable early flooding signal for plants. Previous studies have suggested that, when exposed to flooding stress, this early accumulation of ethylene prepares plants for subsequent O2 crisis. However, little is known about the molecular mechanisms underlying this improved hypoxia tolerance. This thesis aims to further investigate this ethylene-mediated hypoxia tolerance using the model plant Arabidopsis thaliana. The robust system developed in chapter 2 gave us the possibility to assess the mechanism by which ethylene improved hypoxia tolerance. Considering that this early ethylene signal is not only beneficial to seedlings (Arabidopsis Col-0, 4-, 5- and 7-day-old), but also adult plants Rumex palustris, the molecular mechanisms might be distinct due to potential developmental effects. However, this also further emphasized the crucial function of ethylene in early flooding signaling throughout the entire plant life cycle. Additionally, the system also allowed us to uncover the importance of the ethylene signal also in limiting damage upon re-aeration, which is a further challenge for plants after flood waters recede. The transcriptome analysis in this thesis, both the ethylene-mediated hypoxia and reoxygenation responses of 4-day-old Col-0 seedlings (Chapter 3) and the comparison between 4- and 7-day-old seedlings (Chapter 5), allowed us to unravel the molecular changes responsible for the survival differences. Among those biological processes identified, metabolic reprogramming of hormones biosynthesis and signaling, energy metabolism, redox homeostasis and epigenetic modifications were highlighted. Meanwhile, restricted ROS accumulation post-hypoxia resulted enhanced hypoxia survival in chapter 4, suggesting that ethylene-mediated hypoxia tolerance could be linked to the enhanced oxidative stress tolerance upon re-oxygenation. In summary, the findings in this thesis demonstrated the potential ability of plants to benefit from the early flooding signal ethylene in adaptation to hypoxia stress. We identified several ethylene specific responses, including hormones interaction, energy metabolism, redox balance maintenance and epigenetic modifications, which could be facilitating the increased hypoxia survival in Arabidopsis

Ethylene-mediated hypoxia tolerance in Arabidopsis thaliana

Global warming has led to considerable changes in weather patterns over the past decades. Extreme climate events such as flooding, are expected to become even more frequent and severe in the future. Flooding being detrimental to major crop species, will have significant negative effects on global food production. Gas exchange rate is 104 times slower underwater than in the air. Consequently, plant growth underwater suffers from a lack of oxygen (O2) and carbon dioxide, which are essential for respiration and photosynthesis, respectively. The resulting reduction in photosynthesis and respiration lead to a carbohydrate and energy crisis ultimately affecting plant performance. Restricted gas diffusion underwater also results in rapid accumulation of the plant hormone ethylene in flooded plant tissues. Ethylene has been shown to be one of the key regulators of major flood adaptive responses. Unlike other flooding signals such as O2 and light availability that can be variable depending on other factors, ethylene accumulation under flooding conditions will always occur due to physical entrapment. Therefore, it is considered a consistent and reliable early flooding signal for plants. Previous studies have suggested that, when exposed to flooding stress, this early accumulation of ethylene prepares plants for subsequent O2 crisis. However, little is known about the molecular mechanisms underlying this improved hypoxia tolerance. This thesis aims to further investigate this ethylene-mediated hypoxia tolerance using the model plant Arabidopsis thaliana. The robust system developed in chapter 2 gave us the possibility to assess the mechanism by which ethylene improved hypoxia tolerance. Considering that this early ethylene signal is not only beneficial to seedlings (Arabidopsis Col-0, 4-, 5- and 7-day-old), but also adult plants Rumex palustris, the molecular mechanisms might be distinct due to potential developmental effects. However, this also further emphasized the crucial function of ethylene in early flooding signaling throughout the entire plant life cycle. Additionally, the system also allowed us to uncover the importance of the ethylene signal also in limiting damage upon re-aeration, which is a further challenge for plants after flood waters recede. The transcriptome analysis in this thesis, both the ethylene-mediated hypoxia and reoxygenation responses of 4-day-old Col-0 seedlings (Chapter 3) and the comparison between 4- and 7-day-old seedlings (Chapter 5), allowed us to unravel the molecular changes responsible for the survival differences. Among those biological processes identified, metabolic reprogramming of hormones biosynthesis and signaling, energy metabolism, redox homeostasis and epigenetic modifications were highlighted. Meanwhile, restricted ROS accumulation post-hypoxia resulted enhanced hypoxia survival in chapter 4, suggesting that ethylene-mediated hypoxia tolerance could be linked to the enhanced oxidative stress tolerance upon re-oxygenation. In summary, the findings in this thesis demonstrated the potential ability of plants to benefit from the early flooding signal ethylene in adaptation to hypoxia stress. We identified several ethylene specific responses, including hormones interaction, energy metabolism, redox balance maintenance and epigenetic modifications, which could be facilitating the increased hypoxia survival in Arabidopsis

Acoustic diagnosis of mechanical fault feature based on reference signal frequency domain semi-blind extraction

Aiming at fault diagnosis problems caused by complex machinery parts, serious background noises and the application limitations of traditional blind signal processing algorithm to the mechanical acoustic signal processing, a failure acoustic diagnosis based on reference signal frequency domain semi-blind extraction is proposed. Key technologies are introduced: Based on frequency-domain blind deconvolution algorithm, the artificial fish swarm algorithm which is good for global optimization is used to construct improved multi-scale morphological filters which is applicable to mechanical failure in order to weaken the background noises; combining the structural parameters of parts to build a reference signal, complex components blind separation is carried out on the signals after noise reduction paragraph by paragraph by reference signal unit semi-blind extraction algorithm; then the improved KL-distance of complex independent components is employed as distance measure to resolve the permutation, and finally the mechanical fault characteristic signals are extracted and separated. The actual acoustic diagnosis of rolling bearing fault in sound field environment results proves the effectiveness of this algorithm

A study of Kang Youwei's (1859-1927) Guang yizhou shuangji

published_or_final_versionFine ArtsMasterMaster of Philosoph

A new gamboge derivative compound 2 inhibits cancer stem-like cells via suppressing EGFR tyrosine phosphorylation in head and neck squamous cell carcinoma

Cancer stem-like cells represent a population of tumour-initiating cells that lead to the relapse and metastasis of cancer. Conventional anti-cancer therapeutic drugs are usually ineffective in eliminating the cancer stem-like cells. Therefore, new drugs or therapeutic methods effectively targeting cancer stem-like cells are in urgent need to successfully cure cancer. Gamboge is a natural anti-cancer medicine whose pharmacological effects are different from those of conventional chemotherapeutical drugs and they can kill some kinds of cancer cells selectively. In this study, we identified a new gamboge derivative, Compound 2 (C2), which presents eminent suppression effects on cancer cells. Interestingly, when compared with cisplatin (CDDP), C2 effectively suppresses the growth of both cancer stem-like cells and non-cancer stem-like cells derived from head and neck squamous cell carcinoma (HNSCC), inhibiting the formation of tumour spheres and colony in vitro, resulting in the loss of expression of multiple cancer stem cell (CSC)-related molecules in HNSCC. Treating with C2 effectively inhibited the growth of HNSCC in BALB/C nude mice. Further investigation found that C2 notably inhibits the activation of epithelial growth factor receptor and the phosphorylation of its downstream protein kinase homo sapiens v-akt murine thymoma viral oncogene homolog (AKT) in HNSCC, resulting in down-regulation of multiple CSC-related molecules in HNSCC. Our study has demonstrated that C2 effectively inhibits the stem-like property of cancer stem-like cells in HNSCC and may be a hopeful targeting drug in cancer therapy