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"He, Jun"
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ETHYLENE RESPONSE FACTOR 74 (ERF74) plays an essential role in controlling a respiratory burst oxidase homolog D (RbohD)-dependent mechanism in response to different stresses in Arabidopsis
Recent studies indicate that the ETHYLENE RESPONSE FACTOR VII (ERF-VII) transcription factor is an important regulator of osmotic and hypoxic stress responses in plants. However, the molecular mechanism of ERF-VII-mediated transcriptional regulation remains unclear.
Here, we investigated the role of ERF74 (a member of the ERF-VII protein family) by examining the abiotic stress tolerance of an ERF74 overexpression line and a T-DNA insertion mutant using flow cytometry, transactivation and electrophoretic mobility shift assays.
35S::ERF74 showed enhanced tolerance to drought, high light, heat and aluminum stresses, whereas the T-DNA insertion mutant erf74 and the erf74;erf75 double mutant displayed higher sensitivity. Using flow cytometry analysis, we found that erf74 and erf74;erf75 lines lack the reactive oxygen species (ROS) burst in the early stages of various stresses, as a result of the lower expression level of RESPIRATORY BURST OXIDASE HOMOLOG D (RbohD). Furthermore, ERF74 directly binds to the promoter of RbohD and activates its expression under different abiotic stresses. Moreover, induction of stress marker genes and ROS-scavenging enzyme genes under various stress conditions is dependent on the ERF74–RbohD–ROS signal pathway.
We propose a pathway that involves ERF74 acting as an on–off switch controlling an RbohD-dependent mechanism in response to different stresses, subsequently maintaining hydrogen peroxide (H2O2) homeostasis in Arabidopsis.
Journal Article
Small molecule inhibitors targeting the PD-1/PD-L1 signaling pathway
Tumor cells form immune escape and subsequently obtain unlimited proliferation ability due to the abnormal immune surveillance mediated by immune checkpoints. Among this class of immune checkpoints, PD-1/PD-L1 was recognized as an anticancer drug target for many years, and so far, several monoclonal antibodies have achieved encouraging outcome in cancer treatment by targeting the PD-1/PD-L1 signaling pathway. Due to the inherent limitations of antibodies, the development of small molecule inhibitors based on PD-1/PD-L1 signaling pathway is gradually reviving in decades. In this review, we summarized a number of small molecule inhibitors based on three different therapeutic approaches interfering PD-1/PD-L1 signaling pathway: (1) blocking direct interaction between PD-1 and PD-L1; (2) inhibiting transcription and translation of PD-L1; and (3) promoting degradation of PD-L1 protein. The development of these small molecule inhibitors opens a new avenue for tumor immunotherapy based on PD-1/PD-L1 signaling pathway.
Journal Article
LINC01133 as ceRNA inhibits gastric cancer progression by sponging miR-106a-3p to regulate APC expression and the Wnt/β-catenin pathway
Background
Gastric cancer (GC) is a common malignancy and frequent cause of cancer-related death. Long non-coding RNAs (lncRNAs) have emerged as important regulators and tissue-specific biomarkers of multiple cancers, including GC. Recent evidence has indicated that the novel lncRNA LINC01133 plays an important role in cancer progression and metastasis. However, its function and molecular mechanism in GC remain largely unknown.
Methods
LINC01133 expression was detected in 200 GC and matched non-cancerous tissues by quantitative reverse transcription PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of LINC01133 both in vitro and in vivo. Insights into the underlying mechanisms of competitive endogenous RNAs (ceRNAs) were determined by bioinformatics analysis, dual-luciferase reporter assays, quantitative PCR arrays, TOPFlash/FOPFlash reporter assay, luciferase assay, and rescue experiments.
Results
LINC01133 was downregulated in GC tissues and cell lines, and its low expression positively correlated with GC progression and metastasis. Functionally, LINC01133 depletion promoted cell proliferation, migration, and the epithelial–mesenchymal transition (EMT) in GC cells, whereas LINC01133 overexpression resulted in the opposite effects both in vitro and in vivo. Bioinformatics analysis and luciferase assays revealed that miR-106a-3p was a direct target of LINC01133, which functioned as a ceRNA in regulating GC metastasis. Mechanistic analysis demonstrated that miR-106a-3p specifically targeted the adenomatous polyposis coli (APC) gene, and LINC01133/miR-106a-3p suppressed the EMT and metastasis by inactivating the Wnt/β-catenin pathway in an APC-dependent manner.
Conclusions
Our findings suggest that reduced expression of LINC01133 is associated with aggressive tumor phenotypes and poor patient outcomes in GC. LINC01133 inhibits GC progression and metastasis by acting as a ceRNA for miR-106a-3p to regulate APC expression and the Wnt/β-catenin pathway, suggesting that LINC01133 may serve as a potential prognostic biomarker and anti-metastatic therapeutic target for GC.
Journal Article
Everyday Environmental Justice in Payments for Ecosystem Services
Currently, social justice for the management of ecosystem services is promoted widely in international communities. Efforts have increased to develop indicators for justice assessment, but these are relatively static forms of results-oriented analysis without much understanding of the dynamics and pluralities of local justice in the management of ecosystem services. This research uses a novel perspective of everyday environmental justice (EEJ) to examine local practices of environmental justice in two protected areas in China where two different payments for ecosystem services (PES) schemes have been implemented. It demonstrates EEJ as a useful, process-oriented analysis that provides a deeper understanding of peoples’ everyday lives and their environmental management practices within the varied contexts of local justice. Everyday practices of EEJ highlight the spatiotemporal dynamics and plurality of justice, thereby offering a broader and more explicit conception of the distributive, procedural and recognition dimensions of environmental justice in local contexts. The research calls on policymakers and researchers to consider the everyday practices of EEJ with a heightened understanding of the spatiotemporal dynamics of multidimensional justice.
Journal Article
Proteomic Profiling of Mouse Liver following Acute Toxoplasma gondii Infection
Toxoplasma gondii remains a global public health problem. However, its pathophysiology is still not-completely understood particularly the impact of infection on host liver metabolism. We performed iTRAQ-based proteomic analysis to evaluate early liver protein responses in BALB/c mice following infection with T. gondii PYS strain (genotype ToxoDB#9) infection. Our data revealed modification of protein expression in key metabolic pathways, as indicated by the upregulation of immune response and downregulation of mitochondrial respiratory chain, and the metabolism of fatty acids, lipids and xenobiotics. T. gondii seems to hijack host PPAR signaling pathway to downregulate the metabolism of fatty acids, lipids and energy in the liver. The metabolism of over 400 substances was affected by the downregulation of genes involved in xenobiotic metabolism. The top 10 transcription factors used by upregulated genes were Stat2, Stat1, Irf2, Irf1, Sp2, Egr1, Stat3, Klf4, Elf1 and Gabpa, while the top 10 transcription factors of downregulated genes were Hnf4A, Ewsr1, Fli1, Hnf4g, Nr2f1, Pparg, Rxra, Hnf1A, Foxa1 and Foxo1. These findings indicate global reprogramming of the metabolism of the mouse liver after acute T. gondii infection. Functional characterization of the altered proteins may enhance understanding of the host responses to T. gondii infection and lead to the identification of new therapeutic targets.
Journal Article
Incoherent strange metal sharply bounded by a critical doping in Bi2212
In normal metals, macroscopic properties are understood using the concept of quasiparticles. In the cuprate high-temperature superconductors, the metallic state above the highest transition temperature is anomalous and is known as the “strange metal.” We studied this state using angle-resolved photoemission spectroscopy. With increasing doping across a temperatureindependent critical value p
c ∼ 0.19, we observed that near the Brillouin zone boundary, the strange metal, characterized by an incoherent spectral function, abruptly reconstructs into a more conventional metal with quasiparticles. Above the temperature of superconducting fluctuations, we found that the pseudogap also discontinuously collapses at the very same value of p
c. These observations suggest that the incoherent strange metal is a distinct state and a prerequisite for the pseudogap; such findings are incompatible with existing pseudogap quantum critical point scenarios.
Journal Article
Reactive Oxygen Species, Metabolic Plasticity, and Drug Resistance in Cancer
The metabolic abnormality observed in tumors is characterized by the dependence of cancer cells on glycolysis for their energy requirements. Cancer cells also exhibit a high level of reactive oxygen species (ROS), largely due to the alteration of cellular bioenergetics. A highly coordinated interplay between tumor energetics and ROS generates a powerful phenotype that provides the tumor cells with proliferative, antiapoptotic, and overall aggressive characteristics. In this review article, we summarize the literature on how ROS impacts energy metabolism by regulating key metabolic enzymes and how metabolic pathways e.g., glycolysis, PPP, and the TCA cycle reciprocally affect the generation and maintenance of ROS homeostasis. Lastly, we discuss how metabolic adaptation in cancer influences the tumor’s response to chemotherapeutic drugs. Though attempts of targeting tumor energetics have shown promising preclinical outcomes, the clinical benefits are yet to be fully achieved. A better understanding of the interaction between metabolic abnormalities and involvement of ROS under the chemo-induced stress will help develop new strategies and personalized approaches to improve the therapeutic efficiency in cancer patients.
Journal Article
Mechanism, Actuation, Perception, and Control of Highly Dynamic Multilegged Robots: A Review
Multilegged robots have the potential to serve as assistants for humans, replacing them in performing dangerous, dull, or unclean tasks. However, they are still far from being sufficiently versatile and robust for many applications. This paper addresses key points that might yield breakthroughs for highly dynamic multilegged robots with the abilities of running (or jumping and hopping) and self-balancing. First, 21 typical multilegged robots from the last five years are surveyed, and the most impressive performances of these robots are presented. Second, current developments regarding key technologies of highly dynamic multilegged robots are reviewed in detail. The latest leg mechanisms with serial-parallel hybrid topologies and rigid–flexible coupling configurations are analyzed. Then, the development trends of three typical actuators, namely hydraulic, quasi-direct drive, and serial elastic actuators, are discussed. After that, the sensors and modeling methods used for perception are surveyed. Furthermore, this paper pays special attention to the review of control approaches since control is a great challenge for highly dynamic multilegged robots. Four dynamics-based control methods and two model-free control methods are described in detail. Third, key open topics of future research concerning the mechanism, actuation, perception, and control of highly dynamic multilegged robots are proposed. This paper reviews the state of the art development for multilegged robots, and discusses the future trend of multilegged robots.
Journal Article