Energy Efficiency and CO2 Emissions in the Greenhouse Industry: Evidence From Michigan

Resource /Energy Economics and Policy,

Inhibition of APE1/Ref-1 Redox Activity with APX3330 Blocks Retinal Angiogenesis in vitro and in vivo

This study examines the role of APE1/Ref-1 in the retina and its potential as a therapeutic target for inhibiting retinal angiogenesis. APE1/Ref-1 expression was quantified by Western blot. The role of APE1/Ref-1 redox function in endothelial cell in vitro angiogenesis was examined by treating retinal vascular endothelial cells (RVECs) with APX3330, a small molecule inhibitor of APE1/Ref-1 redox activity. In vitro methods included a proliferation assay, a transwell migration assay, a Matrigel tube formation assay, and a Real-Time Cell Analysis (RTCA) using the xCELLigence System. In vivo functional studies of APE1/Ref-1 were carried out by treating very low density lipoprotein (VLDL) receptor knockout mice (Vldlr−/−) with intravitreal injection of APX3330, and subsequent measurement of retinal angiomatous proliferation (RAP)-like neovascularization for one week. APE1/Ref-1 was highly expressed in the retina and in RVECs and pericytes in mice. APX3330 (1–10 μM) inhibited proliferation, migration and tube formation of RVECs in vitro in a dose-dependent manner. Vldlr−/− RVECs were more sensitive to APX3330 than wild-type RVECs. In Vldlr−/− mice, a single intravitreal injection of APX3330 at the onset of RAP-like neovascularization significantly reduced RAP-like neovascularization development. APE1/Ref-1 is expressed in retinal vascular cells. APX3330 inhibits RVEC angiogenesis in vitro and significantly reduces RAP-like neovascularization in Vldlr−/− mice. These data support the conclusion that APE1/Ref-1 redox function is required for retinal angiogenesis. Thus, APE1/Ref-1 may have potential as a therapeutic target for treating neovascular age-related macular degeneration and other neovascular diseases

Role of calcium in the expression of MAP kinase kinases (MKKs) and MAP kinases in tomato flower abscission

The mitogen activated protein kinase (MAPK) cascade is an important intracellular signaling module that functions as a convergent point for crosstalk during stress signaling. In this study, we constructed a phylogenetic tree for MAP kinase kinases (MKKs) and MAP kinases (MPKs) in Arabidopsis and Lycopersicon esculentum (tomato) and found that abscission-related AtMKK4 and AtMKK5, and AtMPK3 and AtMPK6 clustered with LeMKK2, and LeMPK1,and LeMPK2 and LeMPK3, respectively. To investigate whether there was a link between homology and abscission, we studied all the LeMKKs at the messenger ribonucleic acid (mRNA) transcript level. LeMKK2 and its homologue AtMKK4/5 both have roles in regulating abscission. Quantitative real time polymerase chain recation (qRT-PCR) of LeMPK1 and LeMPK2, which are highly homologous to AtMPK3 and AtMPK6, most probably mediate abscission downstream through LeMKK2. Calcium depressed the expression of these genes in the early stages of abscission. Treatment with W7 (a calmodulin inhibitor) indicated that the expression of LeMKKs and LeMPKs depended on calmodulin during tomato flower explant abscission.Keyword: Abscission, calcium, qRT-PCR, MAPK, tomat

Inhibition of APE1/Ref-1 redox activity rescues human retinal pigment epithelial cells from oxidative stress and reduces choroidal neovascularization

The effectiveness of current treatment for age related macular degeneration (AMD) by targeting one molecule is limited due to its multifactorial nature and heterogeneous pathologies. Treatment strategy to target multiple signaling pathways or pathological components in AMD pathogenesis is under investigation for better clinical outcome. Inhibition of the redox function of apurinic endonuclease 1/redox factor-1 (APE1) was found to suppress endothelial angiogenesis and promote neuronal cell recovery, thereby may serve as a potential treatment for AMD. In the current study, we for the first time have found that a specific inhibitor of APE1 redox function by a small molecule compound E3330 regulates retinal pigment epithelium (RPEs) cell response to oxidative stress. E3330 significantly blocked sub-lethal doses of oxidized low density lipoprotein (oxLDL) induced proliferation decline and senescence advancement of RPEs. At the same time, E3330 remarkably decreased the accumulation of intracellular reactive oxygen species (ROS) and down-regulated the productions of monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF), as well as attenuated the level of nuclear factor-κB (NF-κB) p65 in RPEs. A panel of stress and toxicity responsive transcription factors that were significantly upregulated by oxLDL was restored by E3330, including Nrf2/Nrf1, p53, NF-κB, HIF1, CBF/NF-Y/YY1, and MTF-1. Further, a single intravitreal injection of E3330 effectively reduced the progression of laser-induced choroidal neovascularization (CNV) in mouse eyes. These data revealed that E3330 effectively rescued RPEs from oxidative stress induced senescence and dysfunctions in multiple aspects in vitro, and attenuated laser-induced damages to RPE–Bruch׳s membrane complex in vivo. Together with its previously established anti-angiogenic and neuroprotection benefits, E3330 is implicated for potential use for AMD treatment

Lack of spontaneous ocular neovascularization and attenuated laser-induced choroidal neovascularization in IGF-I overexpression transgenic mice

Robust IGF-I overexpression induces ocular angiogenesis in mice. To investigate the effect of subtle IGF-I overexpression, we examined the ocular phenotype of IGF-II promoter-driven IGF-I transgenic mice. Despite 2.5-fold elevation of IGF-I mRNA in the retina and 29 and 52% increase of IGF-I protein in the retina and aqueous humor, respectively, no ocular abnormality was observed in these transgenics. This was correlated with unaltered VEGF mRNA levels in the transgenic retina. The transgene was also associated with an attenuated laser-induced choroidal neovascularization. Differential expression levels and pattern of IGF-I gene may underlie the different retinal phenotypes in different transgenic lines

Metformin suppresses retinal angiogenesis and inflammation in vitro and in vivo

The oral anti-diabetic drug metformin has been found to reduce cardiovascular complications independent of glycemic control in diabetic patients. However, its role in diabetic retinal microvascular complications is not clear. This study is to investigate the effects of metformin on retinal vascular endothelium and its possible mechanisms, regarding two major pathogenic features of diabetic retinopathy: angiogenesis and inflammation. In human retinal vascular endothelial cell culture, metformin inhibited various steps of angiogenesis including endothelial cell proliferation, migration, and tube formation in a dose-dependent manner. Its anti-angiogenic activity was confirmed in vivo that metformin significantly reduced spontaneous intraretinal neovascularization in a very-low-density lipoprotein receptor knockout mutant mouse (p

SurrealDriver: Designing Generative Driver Agent Simulation Framework in Urban Contexts based on Large Language Model

Simulation plays a critical role in the research and development of autonomous driving and intelligent transportation systems. However, the current simulation platforms exhibit limitations in the realism and diversity of agent behaviors, which impede the transfer of simulation outcomes to the real world. In this paper, we propose a generative driver agent simulation framework based on large language models (LLMs), capable of perceiving complex traffic scenarios and providing realistic driving maneuvers. Notably, we conducted interviews with 24 drivers and used their detailed descriptions of driving behavior as chain-of-thought prompts to develop a `coach agent' module, which can evaluate and assist driver agents in accumulating driving experience and developing human-like driving styles. Through practical simulation experiments and user experiments, we validate the feasibility of this framework in generating reliable driver agents and analyze the roles of each module. The results show that the framework with full architect decreased the collision rate by 81.04% and increased the human-likeness by 50%. Our research proposes the first urban context driver agent simulation framework based on LLMs and provides valuable insights into the future of agent simulation for complex tasks.Comment: 12 pages, 8 figure