Publications by authors named "Ningsheng Cai"

Article Synopsis
  • The dopamine D receptor (DR) plays a significant role in controlling the functioning of frontal cortico-striatal neurons through heteromers with the α adrenoceptor (αR), which are found in specific brain regions.
  • Research utilizing advanced techniques revealed a new, functionally important αR-DR heteromer located in cortico-striatal terminals, demonstrating distinct signaling behaviors compared to DR variants.
  • These functional differences suggest that certain DR variants may enhance αR-mediated noradrenergic control, potentially influencing susceptibility to impulse control issues and posttraumatic stress disorder.
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Since severe global warming and related climate issues have been caused by the extensive utilization of fossil fuels, the vigorous development of renewable resources is needed, and transformation into stable chemical energy is required to overcome the detriment of their fluctuations as energy sources. As an environmentally friendly and efficient energy carrier, hydrogen can be employed in various industries and produced directly by renewable energy (called green hydrogen). Nevertheless, large-scale green hydrogen production by water electrolysis is prohibited by its uncompetitive cost caused by a high specific energy demand and electricity expenses, which can be overcome by enhancing the corresponding thermodynamics and kinetics at elevated working temperatures.

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Article Synopsis
  • The dopamine D receptor (DR) is the least understood dopamine receptor subtype, particularly regarding common genetic variations that affect its function.
  • These variations, specifically those with 4 or 7 proline repeats, have been linked to neuropsychiatric disorders like ADHD and substance use disorders, highlighting individual differences in impulse control.
  • Recent research suggests that DR's role in modulating the brain's dopamine and norepinephrine systems could make it a potential therapeutic target for ADHD and other impulse-control-related conditions.
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Article Synopsis
  • The study explores how dopamine D1 and D2 receptor (DR-DR) heteromers can influence the effects of selective dopamine ligands, suggesting their relevance as drug development targets.
  • Researchers demonstrated that three similar dopamine ligands (PG01042, PG01037, and VK4-116) have distinct effects based on DR-DR heteromerization, showing varying roles in signaling.
  • The findings indicate that GPCR heteromers should be considered key targets for drug development, especially for conditions like L-DOPA-induced dyskinesia in Parkinson's disease, rather than focusing solely on individual GPCR components.
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Article Synopsis
  • Recent studies suggest that µ-opioid receptors (MORs) and galanin receptors (GalRs) in the brain work together to enhance the effects of opioids on dopamine.
  • The research reveals that when these receptors are expressed alone, they primarily form homodimers, but when co-expressed, they preferentially create heterotetramers.
  • The formation of these heteromers leads to a significant change in the way the receptors interact with G-proteins, shifting from an inhibitory to a stimulatory response, highlighting the complexity and importance of receptor interactions in signaling pathways.
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Background: It has been hypothesized that heteromers of adenosine A receptors (A2AR) and cannabinoid CB receptors (CB1R) localized in glutamatergic nerve terminals mediate the integration of adenosine and endocannabinoid signaling involved in the modulation of striatal excitatory neurotransmission. Previous studies have demonstrated the existence of A2AR-CB1R heteromers in artificial cell systems. A dependence of A2AR signaling for the Gi protein-mediated CB1R signaling was described as one of its main biochemical characteristics.

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Copper oxide is one of the promising oxygen carrier materials in chemical looping with oxygen uncoupling (CLOU) technology, cycling between Cu₂O and CuO. In this study, a multiscale model was developed to describe the oxidation kinetics of the Cu-based oxygen carrier particle with oxygen, including surface, grain, and particle scale. It was considered that the solid product grows with the morphology of disperse islands on the grain surface, and O₂ contacts with two different kinds of grain surfaces in the grain scale model, that is, Cu₂O surface (solid reactant surface) and CuO surface (solid product surface).

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Several studies found in vitro evidence for heteromerization of dopamine D receptors (D1R) and D receptors (D3R), and it has been postulated that functional D1R-D3R heteromers that are normally present in the ventral striatum mediate synergistic locomotor-activating effects of D1R and D3R agonists in rodents. Based also on results obtained in vitro, with mammalian transfected cells, it has been hypothesized that those behavioral effects depend on a D1R-D3R heteromer-mediated G protein-independent signaling. Here, we demonstrate the presence on D1R-D3R heteromers in the mouse ventral striatum by using a synthetic peptide that selectively destabilizes D1R-D3R heteromers.

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Identifying non-addictive opioid medications is a high priority in medical sciences, but μ-opioid receptors mediate both the analgesic and addictive effects of opioids. We found a significant pharmacodynamic difference between morphine and methadone that is determined entirely by heteromerization of μ-opioid receptors with galanin Gal1 receptors, rendering a profound decrease in the potency of methadone. This was explained by methadone's weaker proficiency to activate the dopaminergic system as compared to morphine and predicted a dissociation of therapeutic versus euphoric effects of methadone, which was corroborated by a significantly lower incidence of self-report of "high" in methadone-maintained patients.

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The two most common polymorphisms of the human DRD4 gene encode a dopamine D receptor (D4R) with four or seven repeats of a proline-rich sequence of 16 amino acids (D4.4R or D4.7R).

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The central adenosine system and adenosine receptors play a fundamental role in the modulation of dopaminergic neurotransmission. This is mostly achieved by the strategic co-localization of different adenosine and dopamine receptor subtypes in the two populations of striatal efferent neurons, striatonigral and striatopallidal, that give rise to the direct and indirect striatal efferent pathways, respectively. With optogenetic techniques it has been possible to dissect a differential role of the direct and indirect pathways in mediating "Go" responses upon exposure to reward-related stimuli and "NoGo" responses upon exposure to non-rewarded or aversive-related stimuli, respectively, which depends on their different connecting output structures and their differential expression of dopamine and adenosine receptor subtypes.

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G protein-coupled receptors (GPCRs), G proteins and adenylyl cyclase (AC) comprise one of the most studied transmembrane cell signaling pathways. However, it is unknown whether the ligand-dependent interactions between these signaling molecules are based on random collisions or the rearrangement of pre-coupled elements in a macromolecular complex. Furthermore, it remains controversial whether a GPCR homodimer coupled to a single heterotrimeric G protein constitutes a common functional unit.

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The poor norepinephrine innervation and high density of Gi/o-coupled α- and α-adrenoceptors in the striatum and the dense striatal dopamine innervation have prompted the possibility that dopamine could be an effective adrenoceptor ligand. Nevertheless, the reported adrenoceptor agonistic properties of dopamine are still inconclusive. In this study, we analyzed the binding of norepinephrine, dopamine, and several compounds reported as selective dopamine D-like receptor ligands, such as the D receptor agonist 7-OH-PIPAT and the D receptor agonist RO-105824, to α-adrenoceptors in cortical and striatal tissue, which express α-adrenoceptors and both α- and α-adrenoceptors, respectively.

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The two highly homologous subtypes of stimulatory G proteins Gαs (Gs) and Gαolf (Golf) display contrasting expression patterns in the brain. Golf is predominant in the striatum, while Gs is predominant in the cortex. Yet, little is known about their functional distinctions.

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Polymorphic variants of the dopamine D receptor gene () have been repeatedly associated with numerous neuropsychiatric disorders. Yet, the functional role of the D receptor and the functional differences of the products of polymorphic variants remained enigmatic. Immunohistochemical and optogenetic-microdialysis experiments were performed in knock-in mice expressing a D receptor with the long intracellular domain of a human polymorphic variant associated with attention deficit hyperactivity disorder (ADHD).

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Unlabelled: The neuropeptide galanin has been shown to interact with the opioid system. More specifically, galanin counteracts the behavioral effects of the systemic administration of μ-opioid receptor (MOR) agonists. Yet the mechanism responsible for this galanin-opioid interaction has remained elusive.

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Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R-OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release.

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The dopamine D1 receptor-D3 receptor (D1R-D3R) heteromer is being considered as a potential therapeutic target for neuropsychiatric disorders. Previous studies suggested that this heteromer could be involved in the ability of D3R agonists to potentiate locomotor activation induced by D1R agonists. It has also been postulated that its overexpression plays a role in L-dopa-induced dyskinesia and in drug addiction.

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Previous studies have shown that dopamine and galanin modulate cholinergic transmission in the hippocampus, but little is known about the mechanisms involved and their possible interactions. By using resonance energy transfer techniques in transfected mammalian cells, we demonstrated the existence of heteromers between the dopamine D(1)-like receptors (D(1) and D(5)) and galanin Gal(1), but not Gal(2) receptors. Within the D(1)-Gal(1) and D(5)-Gal(1) receptor heteromers, dopamine receptor activation potentiated and dopamine receptor blockade counteracted MAPK activation induced by stimulation of Gal(1) receptors, whereas Gal(1) receptor activation or blockade did not modify D(1)-like receptor-mediated MAPK activation.

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Pretreatment with methamphetamine (METH) can attenuate toxicity due to acute METH challenges. The majority of previous reports have focused mainly on the effects of the drug on the striatal dopaminergic system. In the present study, we used a regimen that involves gradual increases in METH administration to rats in order to mimic progressively larger doses of the drug used by some human METH addicts.

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The reduction of nitric oxide using ammonia combined with methane and pulverized coal additives has been studied in a drop tube furnace reactor. Simulated flue gas with 1000 ppm NO(x) and 3.4% excess oxygen was generated by cylinder gas.

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Methamphetamine [METH ("speed")] is an abused psychostimulant that can cause psychotic, cognitive, and psychomotor impairment in humans. These signs and symptoms are thought to be related to dysfunctions in basal ganglionic structures of the brain. To identify possible molecular bases for these clinical manifestations, we first used cDNA microarray technology to measure METH-induced transcriptional responses in the striatum of rats treated with an apoptosis-inducing dose of the drug.

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Methamphetamine is a neurotoxic drug of abuse known to cause cell death both in vitro and in vivo. Nevertheless, the molecular and cellular mechanisms involved in this process remain to be clarified. Herein, we show that methamphetamine-induced apoptosis is associated with early (2 h) overexpression of bax, decreases of mitochondrial membrane potential and oxygen consumption as well as release of cytochrome c from mitochondria.

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