Dopamine D2-receptor neurons in nucleus accumbens regulate sevoflurane anesthesia in mice.

Introduction: The mechanism of general anesthesia remains elusive. In recent years, numerous investigations have indicated that its mode of action is closely associated with the sleep-wake pathway. As a result, this study aimed to explore the involvement of dopamine D2 receptor (D2R) expressing neurons located in the nucleus accumbens (NAc), a critical nucleus governing sleep-wake regulation, in sevoflurane anesthesia. Methods: This exploration was carried out using calcium fiber photometry and optogenetics technology, while utilizing cortical electroencephalogram (EEG), loss of righting reflex (LORR), and recovery of righting reflex (RORR) as experimental indicators. Results: The findings from calcium fiber photometry revealed a decrease in the activity of NAcD2R neurons during the induction phase of sevoflurane anesthesia, with subsequent recovery observed during the anesthesia's emergence phase. Moreover, the activation of NAcD2R neurons through optogenetics technology led to a reduction in the anesthesia induction process and an extension of the arousal process in mice. Conversely, the inhibition of these neurons resulted in the opposite effect. Furthermore, the activation of NAcD2R neurons projecting into the ventral pallidum (VP) via optogenetics demonstrated a shortened induction time for mice under sevoflurane anesthesia. Discussion: In conclusion, our research outcomes suggest that NAcD2R neurons play a promotive role in the sevoflurane general anesthesia process in mice, and their activation can reduce the induction time of anesthesia via the ventral pallidum (VP).

The role of the basal forebrain in general anesthesia.

The basal forebrain is a group of nerve nuclei on the ventral side of the ventral ganglion, composed of γ-aminobutyric acid neurons, glutamatergic neurons, cholinergic neurons, and orexigenic neurons. Previous studies have focused on the involvement of the basal forebrain in regulating reward, learning, movement, sleep-awakening, and other neurobiological behaviors, but its role in the regulation of general anesthesia has not been systematically elucidated. Therefore, the different neuronal subtypes in the basal forebrain and projection pathways in general anesthesia will be discussed in this paper. In this paper, we aim to determine and elaborate on the role of the basal forebrain in general anesthesia and the development of theoretical research and provide a new theory.

Dopamine D1-receptor-expressing pathway from the nucleus accumbens to ventral pallidum-mediated sevoflurane anesthesia in mice.

BACKGROUND: General anesthesia has long been used in clinical practice, but its precise pharmacological effects on neural circuits are not fully understood. Recent investigations suggest that the sleep-wake system may play a role in the reversible loss of consciousness induced by general anesthetics. Studies in mice have shown that microinjection of dopamine receptor 1 (D1R) agonists into the nucleus accumbens (NAc) promotes recovery from isoflurane anesthesia, while microinjection of D1R antagonists has the opposite effect. Furthermore, during the induction and maintenance of sevoflurane anesthesia, there is a significant decrease in extracellular dopamine levels in the NAc, which subsequently increases during the recovery period. These findings suggest the involvement of the NAc in the regulation of general anesthesia. However, the specific role of D1R-expressing neurons in the NAc during general anesthesia and the downstream effect pathways are still not well understood. METHODS: In order to analyze the impact of sevoflurane anesthesia on NAcD1R neurons and the NAcD1R -VP pathway, this study employed calcium fiber photometry to investigate alterations in the fluorescence intensity of calcium signals in dopamine D1-receptor-expressing neurons located in the nucleus accumbens (NAcD1R neurons) and the NAcD1R -VP pathway during sevoflurane anesthesia. Subsequently, optogenetic techniques were utilized to activate or inhibit NAcD1R neurons and their synaptic terminals in the ventral pallidum (VP), aiming to elucidate the role of NAcD1R neurons and the NAcD1R -VP pathway in sevoflurane anesthesia. These experiments were supplemented with electroencephalogram (EEG) recordings and behavioral tests. Lastly, a genetically-encoded fluorescent sensor was employed to observe changes in extracellular GABA neurotransmitters in the VP during sevoflurane anesthesia. RESULTS: Our findings revealed that sevoflurane administration led to the inhibition of NAcD1R neuron population activity, as well as their connections within the ventral pallidum (VP). We also observed a reversible reduction in extracellular GABA levels in the VP during both the induction and emergence phases of sevoflurane anesthesia. Additionally, the optogenetic activation of NAcD1R neurons and their synaptic terminals in the VP resulted in a promotion of wakefulness during sevoflurane anesthesia, accompanied by a decrease in EEG slow wave activity and burst suppression rate. Conversely, the optogenetic inhibition of the NAcD1R -VP pathway exerted opposite effects. CONCLUSION: The NAcD1R -VP pathway serves as a crucial downstream pathway of NAcD1R neurons, playing a significant role in regulating arousal during sevoflurane anesthesia. Importantly, this pathway appears to be associated with the release of GABA neurotransmitters from VP cells.

Use of Nickel Oxide Catalysts (Bunsenites) for In-Situ Hydrothermal Upgrading Process of Heavy Oil.

In this study, Nickel oxide-based catalysts (NixOx) were synthesized and used for the in-situ upgrading process of heavy crude oil (viscosity 2157 mPa·s, and API gravity of 14.1° at 25 °C) in aquathermolysis conditions for viscosity reduction and heavy oil recovery. All characterizations of the obtained nanoparticles catalysts (NixOx) were performed through Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Atomic Force Microscopy (AFM), X-Ray and Diffraction (XRD), and ASAP 2400 analyzer from Micromeritics (USA), methods. Experiments of catalytic and non-catalytic upgrading processes were carried out in a discontinuous reactor at a temperature of 300 °C and 72 bars for 24 h and 2% of catalyst ratio to the total weight of heavy crude oil. XRD analysis revealed that the use of nanoparticles of NiO significantly participated in the upgrading processes (by desulfurization) where different activated form catalysts were observed, such as α-NiS, ß-NiS, Ni3S4, Ni9S8, and NiO. The results of viscosity analysis, elemental analysis, and 13C NMR analysis revealed that the viscosity of heavy crude oil decreased from 2157 to 800 mPa·s, heteroatoms removal from heavy oil ranged from S-4.28% to 3.32% and N-0.40% to 0.37%, and total content of fractions (ΣC8-C25) increased from 59.56% to a maximum of 72.21%, with catalyst-3 thank to isomerization of normal and cyclo-alkanes and dealkylation of lateral chains of aromatics structures, respectively. Moreover, the obtained nanoparticles showed good selectivity, promoting in-situ hydrogenation-dehydrogenation reactions, and hydrogen redistribution over carbons (H/C) is improved, ranging from 1.48 to a maximum of 1.77 in sample catalyst-3. On the other hand, the use of nanoparticle catalysts have also impacted the hydrogen production, where the H2/CO provided from the water gas shift reaction has increased. Nickel oxide catalysts have the potential for in-situ hydrothermal upgrading of heavy crude oil because of their great potential to catalyze the aquathermolysis reactions in the presence of steam.

Regulating the Spin State of Single Noble Metal Atoms by Hydroxyl for Selective Dehydrogenation of CH4 Direct Conversion to CH3OH.

The key scientific challenge for methane (CH4) direct conversion to methanol (CH3OH) is considered to be the prevention of overoxidation of target products, which is restrained by the difficulty in the well-controlled process of selective dehydrogenation. Herein, we take single noble metal atom-anchored hexagonal boron nitride nanosheets with B vacancies (MSA/B1-xN) as the model materials and first propose that the dehydrogenation in the direct conversion of CH4 to CH3OH is highly dependent on the spin state of the noble metal. The results reveal that the noble metal with a higher spin magnetic moment is beneficial to the formation of the spin channels for electron transfer, which boosts the dissociation of C-H bonds. The promoted process of dehydrogenation will lead not only to the effective activation of CH4 but also to the easy overoxidation of CH3OH. More importantly, it is found that the spin state of noble metals can be regulated by the introduction of hydroxyl (OH), which realizes the selective dehydrogenation in the process of CH4 direct conversion to CH3OH. Among them, AgSA/B1-xN exhibits the best performance owing to the dynamic regulation spin state of a single Ag atom by OH. On the one hand, the introduction of OH significantly reduces the energy barrier of C-H bond dissociation by the increase in the spin magnetic moment. On the other hand, the high spin magnetic moment of a single Ag atom during the process of subsequent dehydrogenation can be modulated to nearly zero. As a result, the spin channel for electron transfer between the adsorbed CH3OH and reactive sites is broken, which hinders its overoxidation. This work opens a new path to designing catalysts for selective dehydrogenation by tuning the spin state of local electronic structures.

The role of intracerebral dopamine D1 and D2 receptors in sleep-wake cycles and general anesthesia.

Dopamine (DA), a monoamine neurotransmitter, is synthesized and released mainly by neurons in the ventral tegmental area and the substantia nigra (SN) pars compacta of the midbrain. DA and its receptors are essential for the regulation of arousal, movement, cognition, reward, and other neurobiological behaviors. Arousal, locomotion, cognition, reward, and other neurobiological functions are all regulated by dopamine and its receptors. Dopamine receptors can be divided into D1-like receptors (including D1 and D5) or D2-like receptors (containing D2, D3, and D4), with D1 and D2 receptors (D1Rs, and D2Rs) being the most important. Currently, studies indicated that D1Rs and D2Rs are tightly involved with the process of sleep-wake and general anesthesia, but the specific mechanism remains unclear. In this review, we compiled the most recent findings, mainly focusing on the structure, distribution, and signal pathway of D1Rs and D2Rs in the central nervous system, as well as the involvement of D1Rs and D2Rs in sleep-wake and general anesthesia. Thus, the investigations of the D1Rs and D2Rs will benefit not only better knowledge for how sleep-wake control works but also the mechanism of general anesthesia.

Cerebral structural alterations in the patients undergoing postherpetic neuralgia: A VBM-MRI study.

This study aimed to investigate the changes in gray matter (GM) volume and density in patients with postherpetic neuralgia (PHN). Using voxel-based morphometry (VBM), the differences in cerebral GM volume and concentration between 25 PHN patients and 25 healthy controls with similar gender ratios, ages, and education were compared. Meanwhile, correlation analysis was performed between the value of GM volume/concentration in the brain areas with discrepancy and the visual analog scale (VAS) score/lesion duration. The global GM volume in PHN patients was lower than that of healthy controls, while the total volume of cerebrospinal fluid in PHN patients was higher than that of healthy controls. In PHN patients, the GM volume decreased in the striatum, cerebellum, precentral gyrus, middle frontal gyrus, parahippocampal gyrus, postcentral gyrus, and so forth; the GM concentration decreased in the striatum, insula, middle and posterior cingulate, and superior temporal gyrus. There was a negative correlation between GM concentration in the right parahippocampal gyrus and the VAS in patients with PHN. In PHN patients, GM volume and density in the brain regions involved in nociceptive sensation, pain perception, and integration decreased significantly. The interaction between chronic pain of PHN and alteration of the cerebral structure may contribute to the occurrence and development of PHN.

Efficient design optimization of a miniaturized thermoelectric generator for electrically active implants based on parametric model order reduction.

This research focuses on the design of a miniaturized thermoelectric generator (TEG) for electrically active implants. Its design optimization is performed using the finite element method. A simplified TEG model is obtained by replacing the thermocouple array with a single representative thermopile, which considers the number and fill factor of the thermocouples as parameters. Instead of rebuilding the geometry of a detailed model with multiple thermocouples, the simplified model adapts the material properties of its representative thermopile, facilitating design optimization. We extend the model by integrating the simplified TEG together with a housing inside a human tissue model for thermoelectric analysis. For computation efficiency and applicability of model order reduction (MOR), a thermal model is derived from the thermoelectric one, with the Peltier effect being considered through an effective thermal conductivity. Through parametric MOR, two parametric reduced-order models are generated from the full-scale thermoelectric and thermal model, respectively. Furthermore, we demonstrate the design optimization of TEG both in full-scale and reduced-order model for maximal power output and sufficient voltage output.

Lateral Habenula Glutamatergic Neurons Modulate Isoflurane Anesthesia in Mice.

Since their introduction in the 1840s, one of the largest mysteries of modern anesthesia are how general anesthetics create the state of reversible loss of consciousness. Increasing researchers have shown that neural pathways that regulate endogenous sleep-wake systems are also involved in general anesthesia. Recently, the Lateral Habenula (LHb) was considered as a hot spot for both natural sleep-wake and propofol-induced sedation; however, the role of the LHb and related pathways in the isoflurane-induced unconsciousness has yet to be identified. Here, using real-time calcium fiber photometry recordings in vivo, we found that isoflurane reversibly increased the activity of LHb glutamatergic neurons. Then, we selectively ablated LHb glutamatergic neurons in Vglut2-cre mice, which caused a longer induction time and less recovery time along with a decrease in delta-band power in mice under isoflurane anesthesia. Furthermore, using a chemogenetic approach to specifically activate LHb glutamatergic neurons shortened the induction time and prolonged the recovery time in mice under isoflurane anesthesia with an increase in delta-band power. In contrast, chemogenetic inhibition of LHb glutamatergic neurons was very similar to the effects of selective lesions of LHb glutamatergic neurons. Finally, optogenetic activation of LHb glutamatergic neurons or the synaptic terminals of LHb glutamatergic neurons in the rostromedial tegmental nucleus (RMTg) produced a hypnosis-promoting effect in isoflurane anesthesia with an increase in slow wave activity. Our results suggest that LHb glutamatergic neurons and pathway are vital in modulating isoflurane anesthesia.

Deep Insights into Heavy Oil Upgrading Using Supercritical Water by a Comprehensive Analysis of GC, GC-MS, NMR, and SEM-EDX with the Aid of EPR as a Complementary Technical Analysis.

Upgrading of heavy oil in supercritical water (SCW) was analyzed by a comprehensive analysis of GC, GC-MS, NMR, and SEM-EDX with the aid of electron paramagnetic resonance (EPR) as a complementary technical analysis. The significant changes in the physical properties and chemical compositions reveal the effectiveness of heavy oil upgrading by SCW. Especially, changes of intensities of conventional EPR signals from free radicals (FRs) and paramagnetic vanadyl complexes (VO2+) with SCW treatment were noticed, and they were explained, respectively, to understand sulfur removal mechanism (by FR intensity and environment destruction) and metal removal mechanism (by VO2+ complexes' transformation). For the first time, it was shown that electronic relaxation times extracted from the pulsed EPR measurements can serve as sensitive parameters of SCW treatment. The results confirm that EPR can be used as a complementary tool for analyzing heavy oil upgrading in SCW, even for the online monitoring of oilfield upgrading.

Theoretical Insights into the Catalytic Effect of Transition-Metal Ions on the Aquathermal Degradation of Sulfur-Containing Heavy Oil: A DFT Study of Cyclohexyl Phenyl Sulfide Cleavage.

Steam injection is the most widely used technique for effectively reducing the viscosity of heavy oil in heavy oil production, in which in situ upgrading of heavy oil by aquathermolysis plays an important role. Earlier, transition-metal catalysts have been used for improving the efficiency of steam injection by catalytic aquathermolysis and achieving a higher degree of in situ oil upgrading. However, the unclear mechanism of aquathermolysis makes it difficult to choose efficient catalysts for different types of heavy oil. This theoretical study is aimed at deeply understanding the mechanism of in situ upgrading of sulfur-containing heavy oil and its catalysis. For this purpose, cyclohexyl phenyl sulfide (CPS) is selected as a model compound of sulfur-containing oil components, and, for the first time, a catalytic effect of transition metals on the thermochemistry and kinetics of its aquathermolysis is investigated by the density functional theory (DFT) methods with the use of the Becke three-parameter Lee-Yang-Parr (B3LYP), ωB97X-D, and M06-2X functionals. Calculation results show that the hydrolysis of CPS is characterized by fairly high energy barriers in comparison with other possible reaction routes leading to the cleavage of C-S bonds, while the heterolysis of C-S bonds in the presence of protons has a substantially lower kinetic barrier. According to the theoretical analysis, transition-metal ions significantly reduce the kinetic barrier of heterolysis. The Cu2+ ion outperforms the other investigated metal ions and the hydrogen ion in the calculated rate constant by 5-6 (depending on the metal) and 7 orders of magnitude, respectively. The catalytic activity of the investigated transition-metal ions is arranged in the following sequence, depending on the used DFT functional: Cu2+ ≫ Co2+ ≈ Ni2+ > Fe2+. It is theoretically confirmed that transition-metal ions, especially Cu2+, can serve as effective catalysts in aquathermolysis reactions. The proposed quantum-chemical approach for studying the catalytic aquathermolysis provides a new supplementary theoretical tool that can be used in the development of catalysts for different chemical transformations of heavy oil components in reservoirs due to hydrothermal treatment.

Towards efficient design optimization of a miniaturized thermoelectric generator for electrically active implants via model order reduction and submodeling technique.

Thermoelectric generators (TEG) convert the thermal energy into electrical energy and are under investigation as a power supply for medical implants. To improve the performance of TEG, the design optimization process through finite element model simulation is preferred by biomedical engineers. This paper aims to provide an efficient method of speeding up the design optimization process of TEG. A three-dimensional realistic human torso model incorporating the TEG is investigated, where the internal heat transfer in human tissue is characterized by Pennes bioheat equation. In addition, convection, radiation, and evaporation effects at the skin surface are applied to identify the heat transfer effects between the human body and the environment. To speed up finite element simulation of the large-scale human torso model, projection-based model order reduction (MOR) is applied for generation of a compact but highly accurate model. Parametric MOR (pMOR) further enables generating a parameter-independent compact model. For an efficient design optimization of TEG, this compact human torso model is applied within a thermal submodeling approach. Its temperature distribution results are back-projected and used as boundary conditions for the TEG submodel. The achieved speed-up in simulation time, demonstrated in this work, clearly indicates that the design optimization process of TEG is more efficient with the combination of MOR and submodeling techniques.

System-Level Model and Simulation of a Frequency-Tunable Vibration Energy Harvester.

In this paper, we present a macroscale multiresonant vibration-based energy harvester. The device features frequency tunability through magnetostatic actuation on the resonator. The magnetic tuning scheme uses external magnets on linear stages. The system-level model demonstrates autonomous adaptation of resonance frequency to the dominant ambient frequencies. The harvester is designed such that its two fundamental modes appear in the range of (50,100) Hz which is a typical frequency range for vibrations found in industrial applications. The dual- frequency characteristics of the proposed design together with the frequency agility result in an increased operative harvesting frequency range. In order to allow a time-efficient simulation of the model, a reduced order model has been derived from a finite element model. A tuning control algorithm based on maximum-voltage tracking has been implemented in the model. The device was characterized experimentally to deliver a power output of 500 µW at an excitation level of 0.5 g at the respected frequencies of 63.3 and 76.4 Hz. In a design optimization effort, an improved geometry has been derived. It yields more close resonance frequencies and optimized performance.

The Locus Coeruleus Modulates Intravenous General Anesthesia of Zebrafish via a Cooperative Mechanism.

How general anesthesia causes loss of consciousness has been a mystery for decades. It is generally thought that arousal-related brain nuclei, including the locus coeruleus (LC), are involved. Here, by monitoring locomotion behaviors and neural activities, we developed a larval zebrafish model for studying general anesthesia induced by propofol and etomidate, two commonly used intravenous anesthetics. Local lesion of LC neurons via two-photon laser-based ablation or genetic depletion of norepinephrine (NE; a neuromodulator released by LC neurons) via CRISPR/Cas9-based mutation of dopamine-ß-hydroxylase (dbh) accelerates induction into and retards emergence from general anesthesia. Mechanistically, in vivo whole-cell recording revealed that both anesthetics suppress LC neurons' activity through a cooperative mechanism, inhibiting presynaptic excitatory inputs and inducing GABAA receptor-mediated hyperpolarization of these neurons. Thus, our study indicates that the LC-NE system plays a modulatory role in both induction of and emergence from intravenous general anesthesia.

Effects of Ketamine on Neuronal Spontaneous Excitatory Postsynaptic Currents and Miniature Excitatory Postsynaptic Currents in the Somatosensory Cortex of Rats.

BACKGROUND: Ketamine is a commonly used intravenous anesthetic which produces dissociation anesthesia, analgesia, and amnesia. The mechanism of ketamine-induced synaptic inhibition in high-level cortical areas is still unknown. We aimed to elucidate the effects of different concentrations of ketamine on the glutamatergic synaptic transmission of the neurons in the primary somatosensory cortex by using the whole-cell patch-clamp method. METHODS: Sprague-Dawley rats (11-19 postnatal days, n=36) were used to obtain brain slices (300 µM). Spontaneous excitatory postsynaptic currents (data from 40 neurons) were recorded at a command potential of -70 mV in the presence of bicuculline (a competitive antagonist of GABAA receptors, 30 µM) and strychnine (glycine receptor antagonist, 30 µM). Miniature excitatory postsynaptic currents (data from 40 neurons) were also recorded when 1 µM of tetrodotoxin was added into the artificial cerebrospinal fluid. We used GraphPad Prism5for statistical analysis. Significant differences in the mean amplitude and frequency were tested using the Student paired 2-tailed t test. Values of P<0.05 were considered significant. RESULTS: Different concentrations of ketamine inhibited the frequency and amplitude of the spontaneous excitatory postsynaptic currents as well as the amplitude of the miniature excitatory postsynaptic currents in a concentration-dependent manner, but they exerted no significant effect on the frequency of the miniature excitatory postsynaptic currents. CONCLUSION: Ketamine inhibited the excitatory synaptic transmission of the neurons in the primary somatosensory cortex. The inhibition may have been mediated by a reduction in the sensitivity of the postsynaptic glutamatergic receptors.

Effects of propofol on the dopamine, metabolites and GABAA receptors in media prefrontal cortex in freely moving rats.

Recent researches indicate that the mechanism of anesthetic induce loss of consciousness (LOC) is related to dopamine dysfunction in the media prefrontal cortex (mPFC). Given GABAA receptors are the main target for commonly intravenous anesthetic propofol, in this study, we test whether that propofol induced LOC mediate by GABAA receptors in mPFC through altering the dopamine and its metabolites. In the present study, we use Loss of righting reflex (LORR) and Recovery of righting reflex (RORR) as measure to respectively reflect the status of unconsciousness and consciousness recovery in rats. We imitate the clinical anesthesia process, found the minimum of induction and maintenance concentration of propofol respectively was 11 mg/kg and 40 mg/kg per hour. Then, microdialysis technique was used to observe the change of dopamine (DA), metabolites 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) before and after intravenous infusion of propofol from caudal vein of freely moving rats. The results showed that propofol can increase the level of DOPAC except HVA, and reduced the level of DA in mPFC during unconsciousness of rats. DOPAC and DA return to the baseline level when the rats began to regain consciousness. Local reverse dialysis infusion of GABAA receptor antagonist GABAzine (50 uM) in mPFC can promote the time of LORR, reduce the time of RORR, and increase the basal level of DOPAC. With this condition, propofol increased HVA instead of DOPAC, whereas the DA was still reduced. These results suggest that propofol may induce unconsciousness by directly inhibiting dopamine release in the mPFC, and this effect does not be mediated by GABAA receptor in mPFC.