Orexin-A protects against oxygen-glucose deprivation/reoxygenation-induced cell damage by inhibiting endoplasmic reticulum stress-mediated apoptosis via the Gi and PI3K signaling pathways

The neuropeptide orexin-A (OXA) has a neuroprotective effect, acting as an anti-apoptotic factor in response to multiple stimuli. Apoptosis induced by endoplasmic reticulum stress (ERS) underlies oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell damage, an in vitro model of ischemia/reperfusion injury. However, that OXA inhibits ERS-induced apoptosis in the OGD/R model has not been reported. In the present study, we investigated the neuroprotective effect of OXA (0.1 μM) on OGD/R-induced damage in the human neuroblastoma cell line SH-SY5Y. After OXA treatment following 4 h oxygen-glucose deprivation (OGD) and then 4 h reoxygenation (R), cell morphology, viability, and apoptosis were analyzed by histology, Cell Counting Kit-8 assay, and flow cytometry, respectively. Western blotting was used to measure expression levels of ERS- and apoptosis-related proteins. To determine signaling pathways involved in OXA-mediated neuroprotection, the Gi pathway inhibitor pertussis toxin (PTX; 100 ng/mL) and PI3K inhibitor LY294002 (LY; 10 μM) were added. In addition, in order to prove the specificity of these characteristics, the OXA antagonist Suvorexant (DORA; Ki of 0.55 nM and 0.35 nM for OX1R and OX2R) was used for intervention. Our results showed that OGD/R induced cell damage, manifested as morphological changes and a significant decrease in viability. Furthermore, Western blotting detected an increase in ERS-related proteins GRP78, p-IRE1α, p-JNK, and Cleaved caspase-12, as well as apoptosis-related proteins Cleaved caspase-3 and Bax, and a decrease in the anti-apoptosis factor Bcl-2. OXA intervention alleviated the degree of cellular damage, and protein expression was also reversed. In addition, the protective effect of OXA was reduced by adding PTX and LY. Meanwhile, after the use of DORA, changes in the expression of related proteins were detected, and it was found that the protective effect of OXA was weakened. Collectively, our results indicate that OXA has a neuroprotective effect on OGD/R-induced cell damage by inhibiting ERS-induced apoptosis through the combined action of Gi and PI3K signaling pathways. These findings help to clarify the mechanism underlying the neuroprotective action of OXA, which should aid the development of further candidate drugs, and provide a new therapeutic direction for the treatment of ischemic stroke

Research on computer vision application in industry field: focus on distribution network engineering

The operation of distribution networks is currently facing potential safety and quality defects that pose significant hazards. One solution to strengthen management, reduce manual workload, and improve efficiency and quality is by applying deep detection networks for dynamic defect detection in distribution network engineering. To start, defects in distribution network engineering are classified. Then, advanced deep detection networks and their applications in dynamic defect detection are researched and analyzed, along with a review of existing research. Key issues and their solutions for deep detection network application in dynamic defect detection in distribution network engineering are summarized. Finally, future research directions are explored to provide valuable references for future studies

Optimizing the scale of markets for water quality trading

Applying market approaches to environmental regulations requires establishing a spatial scale for trading. Spatially large markets usually increase opportunities for abatement cost savings but increase the potential for pollution damages (hot spots), vice versa for spatially small markets. We develop a coupled hydrologic-economic modeling approach for application to point source emissions trading by a large number of sources and apply this approach to the wastewater treatment plants (WWTPs) within the watershed of the second largest estuary in the U.S. We consider two different administrative structures that govern the trade of emission permits: one-for-one trading (the number of permits required for each unit of emission is the same for every WWTP) and trading ratios (the number of permits required for each unit of emissions varies across WWTP). Results show that water quality regulators should allow trading to occur at the river basin scale as an appropriate first-step policy, as is being done in a limited number of cases via compliance associations. Larger spatial scales may be needed under conditions of increased abatement costs. The optimal scale of the market is generally the same regardless of whether one-for-one trading or trading ratios are employed

Transmembrane peptide 4 and 5 of APJ are essential for its heterodimerization with OX1R

Increasing evidence indicates some G protein-coupled receptors function as a heterodimer, which provide a novel target for therapeutics investigation. However, study on the receptor-receptor interaction interface, a potent target on interfering dimer formation, are still limited. Here, using bioluminescence resonance energy transfer (BRET) combined with co-immunoprecipitation (Co-IP), we found a new constitutive GPCR heterodimer, apelin receptor (APJ)-orexin receptor type 1 (OX1R). Both APJ and OX1R co-internalized when constantly subjected to cognate agonist (apelin-13 or orexin-A) specific to either protomer. Combined with BRET and immunostaining, the in vitro synthesized transmembrane peptides (TMs) interfering experiments suggests that TM4 and 5 of APJ act as the interaction interface of the APJ-OX1R heterodimer, and co-internalization could be disrupted by these peptides as well. Our study not only provide new evidence on GPCR heterodimerization, but address a novel heterodimerization interface, which can be severed as a potential pharmacological target

Effects of NaHSO3 on Cellular Metabolic Energy, Photosynthesis and Growth of Iris pseudacorus L.

According to the law of energy conservation, the energy consumed by plants to resist adversity is equal to the difference between photosynthetic energy and growth energy consumption and cellular metabolic energy in plants. The cellular metabolic energy is calculated based on the electrical signals in plants. This study mainly investigated the effect of NaHSO3 on the growth and energy traits of the aquatic plant Iris pseudacorus L. and explored the effect of NaHSO3 on energy consumption in the process of plant development. In this study, NaHSO3 was used for simulating sulfur pollution in water medium. During the 20-day experiment period, the response of I. pseudocorus to the polluted water sources simulated by adding different concentrations of NaHSO3 (0, 0.5, 2, 4, 10 mmol·L−1) was monitored, and the internal mechanism of the relationship between the forms of energy and the removal of sulfur pollution was analyzed. After the 20-day exposure experiment, the growth and nutrient absorption capacity were significantly inhibited, and this inhibition proved to be concentration-dependent. In addition, high concentrations (4 and 10 mmol·L−1) of NaHSO3 might affect photosynthesis by disrupting cell membrane systems as it may interfere with membrane proteins and lipids and thus alter membrane integrity. Therefore, the cellular metabolic energy was increased and the sulfur absorption by I. pseudocorus was promoted under the low concentration (0.5 mmol/L−1) compared with the control, the role of NaHSO3 in promoting the growth of I. pseudocorus is much greater than its toxic effect under low concentrations. Under the hydroponic culture which contained 0.5 mmol·L−1 of NaHSO3, I. pseudocorus grew well and absorbed more sulfur. The results can be used as a reference for the cultivation of aquatic plants dealing with sulfur pollution, and dilution strategy can be set up to treat water medium that is seriously polluted with sulfur

Identifying climatic constraints of US agriculture

The paper estimates the countervailing climatic factors driving the timing of US corn planting decisions. We combine very diverse sources of data, including daily fine-scale satellite-derived information, to infer the timing of planting decisions over the past 30 years at the county-level. We match this information with daily data on temperature and soil moisture conditions to assess their contributions to the planting decision. Using a panel logit model we find that warmer spring temperatures increase the probability of planting, while extremely low or high levels of moisture reduce it. We find that the levels of moisture necessary to fully offset the season-expanding effect of a temperature rise of 3ºC would need to be very extreme, suggesting that the growing season for corn is likely to expand with climate change

The orexin/receptor system : molecular mechanism and therapeutic potential for neurological diseases

Orexins, also known as hypocretins, are two neuropeptides secreted from orexin-containing neurons, mainly in the lateral hypothalamus (LH). Orexins orchestrate their effects by binding and activating two G-protein-coupled receptors (GPCRs), orexin receptor type 1 (OX1R) and type 2 (OX2R). Orexin/receptor pathways play vital regulatory roles in many physiological processes, especially feeding behavior, sleep-wake rhythm, reward and addiction and energy balance. Furthermore several reports showed that orexin/receptor pathways are involved in pathological processes of neurological diseases such as narcolepsy, depression, ischemic stroke, drug addiction and Alzheimer's disease (AD). This review article summarizes the expression patterns, physiological functions and potential molecular mechanisms of the orexin/receptor system in neurological diseases, providing an overall framework for considering these pathways from the standpoints of basic research and clinical treatment of neurological diseases

Effects of NaHSO₃ on Cellular Metabolic Energy, Photosynthesis and Growth of <i>Iris pseudacorus</i> L.

According to the law of energy conservation, the energy consumed by plants to resist adversity is equal to the difference between photosynthetic energy and growth energy consumption and cellular metabolic energy in plants. The cellular metabolic energy is calculated based on the electrical signals in plants. This study mainly investigated the effect of NaHSO3 on the growth and energy traits of the aquatic plant Iris pseudacorus L. and explored the effect of NaHSO3 on energy consumption in the process of plant development. In this study, NaHSO3 was used for simulating sulfur pollution in water medium. During the 20-day experiment period, the response of I. pseudocorus to the polluted water sources simulated by adding different concentrations of NaHSO3 (0, 0.5, 2, 4, 10 mmol·L−1) was monitored, and the internal mechanism of the relationship between the forms of energy and the removal of sulfur pollution was analyzed. After the 20-day exposure experiment, the growth and nutrient absorption capacity were significantly inhibited, and this inhibition proved to be concentration-dependent. In addition, high concentrations (4 and 10 mmol·L−1) of NaHSO3 might affect photosynthesis by disrupting cell membrane systems as it may interfere with membrane proteins and lipids and thus alter membrane integrity. Therefore, the cellular metabolic energy was increased and the sulfur absorption by I. pseudocorus was promoted under the low concentration (0.5 mmol/L−1) compared with the control, the role of NaHSO3 in promoting the growth of I. pseudocorus is much greater than its toxic effect under low concentrations. Under the hydroponic culture which contained 0.5 mmol·L−1 of NaHSO3, I. pseudocorus grew well and absorbed more sulfur. The results can be used as a reference for the cultivation of aquatic plants dealing with sulfur pollution, and dilution strategy can be set up to treat water medium that is seriously polluted with sulfur

Ghrelin through GHSR1a and OX1R heterodimers reveals a Gαs–cAMP-cAMP response element binding protein signaling pathway in vitro

Growth hormone secretagogue receptor 1α (GHSR1a) and Orexin 1 receptor (OX1R) are involved in various important physiological processes, and have many similar characteristics in function and distribution in peripheral tissues and the central nervous system. We explored the possibility of heterodimerization between GHSR1a and OX1R and revealed a signal transduction pathway mechanism. In this study, bioluminescence and fluorescence resonance energy transfer and co-immunoprecipitation (Co-IP) analyses were performed to demonstrate the formation of functional GHSR1a/OX1R heterodimers. This showed that a peptide corresponding to the 5-transmembrane domain of OX1R impaired heterodimer construction. We found that ghrelin stimulated GHSR1a/OX1R heterodimer cells to increase the activation of Gαs protein, compared to the cells that express GHSR1a. Stimulation of GHSR1a/OX1R heterodimers with orexin-A did not alter GPCR interactions with Gα protein subunits. GHSR1a/OX1R heterodimers induced Gαs and downstream signaling pathway activity, including increase of cAMP-response element luciferase reporter activity and cAMP levels. In addition, ghrelin induced a higher proliferation rate in SH-SY5Y cells than in controls. This suggests that ghrelin GHSR1a/OX1R heterodimers promotes an upregulation of a Gαs-cAMP-cAMP-responsive element signaling pathway in vitro and an increase in neuroblastoma cell proliferation