Correction: Contrast of oropharyngeal leak pressure and clinical performance of I-gel™ and LMA ProSeal™ in patients: A meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0278871.].

Astrocytes modulate a specific paraventricular thalamus-prefrontal cortex projection to enhance consciousness recovery from anesthesia.

Current anesthetic theory is mostly based on neurons and/or neuronal circuits. A role for astrocytes also has been shown in promoting recovery from volatile anesthesia, while the exact modulatory mechanism and/or the molecular target in astrocytes is still unknown. In this study, by animal models in male mice and electrophysiological recordings in vivo and in vitro, we found that activating astrocytes of paraventricular thalamus (PVT) and/or knocking down PVT astrocytic Kir4.1 promoted the consciousness recovery from sevoflurane anesthesia. Single-cell RNA sequencing of PVT reveals two distinct cellular subtypes of glutamatergic neurons: PVT GRM and PVT ChAT neurons. Patch-clamp recording results proved astrocytic Kir4.1-mediated modulation of sevoflurane on PVT mainly worked on PVT ChAT neurons, which projected mainly to the mPFC. In summary, our findings support the novel conception that there is a specific PVT-prefrontal cortex projection involved in consciousness recovery from sevoflurane anesthesia, which mediated by the inhibition of sevoflurane on PVT astrocytic Kir4.1 conductance.Significance Statement How volatile anesthetics work is not fully understood. Here, we demonstrate that the commonly used volatile anesthetic sevoflurane can inhibit astrocytic Kir4.1 conductance in PVT, which enhances neuronal firing of PVT neurons. Additionally, by single-cell sequencing, cholinergic neurons in the PVT (PVT ChAT ) are the neuronal substrates for astrocytic modulation in volatile anesthesia, which directly project to prefrontal cortex. Behaviorally, the modulation of astrocytes on PVT ChAT promotes electroencephalogram (EEG) transition of prefrontal cortex; and then accelerates emergence from sevoflurane anesthesia. In summary, this study is the first to identify that astrocytic Kir4.1 in wakeful nuclei is involved in consciousness recovery from volatile anesthetics, as well as the subcellular mechanism.

Sodium Leak Channel in Glutamatergic Neurons of the Lateral Parabrachial Nucleus Helps to Maintain Respiratory Frequency Under Sevoflurane Anesthesia.

The lateral parabrachial nucleus (PBL) is implicated in the regulation of respiratory activity. Sodium leak channel (NALCN) mutations disrupt the respiratory rhythm and influence anesthetic sensitivity in both rodents and humans. Here, we investigated whether the NALCN in PBL glutamatergic neurons maintains respiratory function under general anesthesia. Our results showed that chemogenetic activation of PBL glutamatergic neurons increased the respiratory frequency (RF) in mice; whereas chemogenetic inhibition suppressed RF. NALCN knockdown in PBL glutamatergic neurons but not GABAergic neurons significantly reduced RF under physiological conditions and caused more respiratory suppression under sevoflurane anesthesia. NALCN knockdown in PBL glutamatergic neurons did not further exacerbate the respiratory suppression induced by propofol or morphine. Under sevoflurane anesthesia, painful stimuli rapidly increased the RF, which was not affected by NALCN knockdown in PBL glutamatergic neurons. This study suggested that the NALCN is a key ion channel in PBL glutamatergic neurons that maintains respiratory frequency under volatile anesthetic sevoflurane but not intravenous anesthetic propofol.

Activity of the Sodium Leak Channel Maintains the Excitability of Paraventricular Thalamus Glutamatergic Neurons to Resist Anesthetic Effects of Sevoflurane in Mice.

BACKGROUND: Stimulation of the paraventricular thalamus has been found to enhance anesthesia recovery; however, the underlying molecular mechanism by which general anesthetics modulate paraventricular thalamus is unclear. This study aimed to test the hypothesis that the sodium leak channel (NALCN) maintains neuronal activity in the paraventricular thalamus to resist anesthetic effects of sevoflurane in mice. METHODS: Chemogenetic and optogenetic manipulations, in vivo multiple-channel recordings, and electroencephalogram recordings were used to investigate the role of paraventricular thalamus neuronal activity in sevoflurane anesthesia. Virus-mediated knockdown and/or overexpression was applied to determine how NALCN influenced excitability of paraventricular thalamus glutamatergic neurons under sevoflurane. Viral tracers and local field potentials were used to explore the downstream pathway. RESULTS: Single neuronal spikes in the paraventricular thalamus were suppressed by sevoflurane anesthesia and recovered during emergence. Optogenetic activation of paraventricular thalamus glutamatergic neurons shortened the emergence period from sevoflurane anesthesia, while chemogenetic inhibition had the opposite effect. Knockdown of the NALCN in the paraventricular thalamus delayed the emergence from sevoflurane anesthesia (recovery time: from 24 ± 14 to 64 ± 19 s, P < 0.001; concentration for recovery of the righting reflex: from 1.13% ± 0.10% to 0.97% ± 0.13%, P < 0.01). As expected, the overexpression of the NALCN in the paraventricular thalamus produced the opposite effects. At the circuit level, knockdown of the NALCN in the paraventricular thalamus decreased the neuronal activity of the nucleus accumbens, as indicated by the local field potential and decreased single neuronal spikes in the nucleus accumbens. Additionally, the effects of NALCN knockdown in the paraventricular thalamus on sevoflurane actions were reversed by optical stimulation of the nucleus accumbens. CONCLUSIONS: Activity of the NALCN maintains the excitability of paraventricular thalamus glutamatergic neurons to resist the anesthetic effects of sevoflurane in mice.

γ-Aminobutyric Acid-Ergic Development Contributes to the Enhancement of Electroencephalogram Slow-Delta Oscillations Under Volatile Anesthesia in Neonatal Rats.

BACKGROUND: General anesthetics (eg, propofol and volatile anesthetics) enhance the slow-delta oscillations of the cortical electroencephalogram (EEG), which partly results from the enhancement of (γ-aminobutyric acid [GABA]) γ-aminobutyric acid-ergic (GABAergic) transmission. There is a GABAergic excitatory-inhibitory shift during postnatal development. Whether general anesthetics can enhance slow-delta oscillations in the immature brain has not yet been unequivocally determined. METHODS: Perforated patch-clamp recording was used to confirm the reversal potential of GABAergic currents throughout GABAergic development in acute brain slices of neonatal rats. The power density of the electrocorticogram and the minimum alveolar concentrations (MAC) of isoflurane and/or sevoflurane were measured in P4-P21 rats. Then, the effects of bumetanide, an inhibitor of the Na + -K + -2Cl - cotransporter (NKCC1) and K + -Cl - cotransporter (KCC2) knockdown on the potency of volatile anesthetics and the power density of the EEG were determined in vivo. RESULTS: Reversal potential of GABAergic currents were gradually hyperpolarized from P4 to P21 in cortical pyramidal neurons. Bumetanide enhanced the hypnotic effects of volatile anesthetics at P5 (for MAC LORR , isoflurane: 0.63% ± 0.07% vs 0.81% ± 0.05%, 95% confidence interval [CI], -0.257 to -0.103, P < .001; sevoflurane: 1.46% ± 0.12% vs 1.66% ± 0.09%, 95% CI, -0.319 to -0.081, P < .001); while knockdown of KCC2 weakened their hypnotic effects at P21 in rats (for MAC LORR , isoflurane: 0.58% ± 0.05% to 0.77% ± 0.20%, 95% CI, 0.013-0.357, P = .003; sevoflurane: 1.17% ± 0.04% to 1.33% ± 0.04%, 95% CI, 0.078-0.244, P < .001). For cortical EEG, slow-delta oscillations were the predominant components of the EEG spectrum in neonatal rats. Isoflurane and/or sevoflurane suppressed the power density of slow-delta oscillations rather than enhancement of it until GABAergic maturity. Enhancement of slow-delta oscillations under volatile anesthetics was simulated by preinjection of bumetanide at P5 (isoflurane: slow-delta changed ratio from -0.31 ± 0.22 to 1.57 ± 1.15, 95% CI, 0.67-3.08, P = .007; sevoflurane: slow-delta changed ratio from -0.46 ± 0.25 to 0.95 ± 0.97, 95% CI, 0.38-2.45, P = .014); and suppressed by KCC2-siRNA at P21 (isoflurane: slow-delta changed ratio from 16.13 ± 5.69 to 3.98 ± 2.35, 95% CI, -18.50 to -5.80, P = .002; sevoflurane: slow-delta changed ratio from 0.13 ± 2.82 to 3.23 ± 2.49, 95% CI, 3.02-10.79, P = .003). CONCLUSIONS: Enhancement of cortical EEG slow-delta oscillations by volatile anesthetics may require mature GABAergic inhibitory transmission during neonatal development.

Sodium Leak Channel in Glutamatergic Neurons of the Lateral Parabrachial Nucleus Modulates Inflammatory Pain in Mice.

Elevated excitability of glutamatergic neurons in the lateral parabrachial nucleus (PBL) is associated with the pathogenesis of inflammatory pain, but the underlying molecular mechanisms are not fully understood. Sodium leak channel (NALCN) is widely expressed in the central nervous system and regulates neuronal excitability. In this study, chemogenetic manipulation was used to explore the association between the activity of PBL glutamatergic neurons and pain thresholds. Complete Freund's adjuvant (CFA) was used to construct an inflammatory pain model in mice. Pain behaviour was tested using von Frey filaments and Hargreaves tests. Local field potential (LFP) was used to record the activity of PBL glutamatergic neurons. Gene knockdown techniques were used to investigate the role of NALCN in inflammatory pain. We further explored the downstream projections of PBL using cis-trans-synaptic tracer virus. The results showed that chemogenetic inhibition of PBL glutamatergic neurons increased pain thresholds in mice, whereas chemogenetic activation produced the opposite results. CFA plantar modelling increased the number of C-Fos protein and NALCN expression in PBL glutamatergic neurons. Knockdown of NALCN in PBL glutamatergic neurons alleviated CFA-induced pain. CFA injection induced C-Fos protein expression in central nucleus amygdala (CeA) neurons, which was suppressed by NALCN knockdown in PBL glutamatergic neurons. Therefore, elevated expression of NALCN in PBL glutamatergic neurons contributes to the development of inflammatory pain via PBL-CeA projections.

Néel-type optical target skyrmions inherited from evanescent electromagnetic fields with rotational symmetry.

Optical skyrmions have recently attracted growing interest due to their potential applications in deep-subwavelength imaging and nanometrology. While optical skyrmions have been successfully demonstrated using different field vectors, the study of their generation and control, as well as their general correlation with electromagnetic (EM) fields, is still in its infancy. Here, we theoretically propose that evanescent transverse-magnetic-polarized (TM-polarized) EM fields with rotational symmetry are actually Néel-type optical target skyrmions of the electric field vectors. Such optical target skyrmions are independent of the operation frequency and medium. Our proposal was verified by numerical simulations and real-space nano-imaging experiments performed on a graphene monolayer, where the target skyrmions could be as small as ∼100 nm in diameter. The results can therefore not only further our understanding of the formation mechanisms of EM topological textures, but also provide guidelines for the facile construction of EM skyrmions that may impact future information technologies.

In-plane hyperbolic polariton tuners in terahertz and long-wave infrared regimes.

One of the main bottlenecks in the development of terahertz (THz) and long-wave infrared (LWIR) technologies is the limited intrinsic response of traditional materials. Hyperbolic phonon polaritons (HPhPs) of van der Waals semiconductors couple strongly with THz and LWIR radiation. However, the mismatch of photon - polariton momentum makes far-field excitation of HPhPs challenging. Here, we propose an In-Plane Hyperbolic Polariton Tuner that is based on patterning van der Waals semiconductors, here α-MoO3, into ribbon arrays. We demonstrate that such tuners respond directly to far-field excitation and give rise to LWIR and THz resonances with high quality factors up to 300, which are strongly dependent on in-plane hyperbolic polariton of the patterned α-MoO3. We further show that with this tuner, intensity regulation of reflected and transmitted electromagnetic waves, as well as their wavelength and polarization selection can be achieved. Our results can help the development of THz and LWIR miniaturized devices.

Contrast of oropharyngeal leak pressure and clinical performance of I-gel™ and LMA ProSeal™ in patients: A meta-analysis.

BACKGROUND: Conflicting outcomes have been reported for the i-gel™ and laryngeal mask airway (LMA) ProSeal™ in children and adults during general anesthesia. Randomized controlled trials (RCTs) that yielded wide contrast outcomes between i-gel™ and LMA ProSeal™ were included in this meta-analysis. METHODS: Two authors independently identified RCTs that compared i-gel™ with LMA ProSeal™ among patients receiving general anesthesia by performing searches in EMBASE, Cochrane, PubMed, and ScienceDirect. Discussion was adopted to resolve disagreements. Data were counted with Review Manger 5.3 and pooled by applying weighted mean difference (MD) and rlsk ratio (RR), and related 95% confidence intervals. RESULTS: A total of 33 RCTs with 2605 patients were included in the meta-analysis. I-gel™ provided a considerably lower oropharyngeal leak pressure [weighted average diversity (MD) = -1.53 (-2.89, -0.17), P = 0.03], incidence of blood staining on the supraglottic airway devices [RR = 0.44, (0.28, 0.69), P = 0.0003], sore throat [RR = 0.31 (0.18, 0.52), P<0.0001], and a short insertion time [MD = -5.61 (-7.71, -3.51), P<0.00001] than LMA ProSeal™. Compared with LMA ProSeal™, i-gel™ offered a significantly higher first-insertion success rate [RR = 1.03 (1.00, 1.06), P = 0.03] and ease of insertion [RR = 1.06 (1.01, 1.11), P = 0.03]. The gastric-tube-placement first insertion rate [RR = 1.04 (0.99, 1.10), P = 0.11], laryngospasm [RR = 0.76 (0.17, 3.31), P = 0.72], and cough [RR = 1.30 (0.49, 3.44), P = 0.60] between the two devices were similar. CONCLUSIONS: Both devices could achieve a good seal to provide adequate ventilation. Compared with the used LMA ProSeal™, the i-gel™ was found to have fewer complications (blood stainning, sore throat) and offers certain advantages (short insertion time, higher first-insertion success rate and ease of insertion) in patients under general anesthesia.

WS2-Flake-Sandwiched, Au-Nanodisk-Enabled High-Quality Fabry-Pérot Nanoresonators for Photoluminescence Modulation.

The increasing demand for compact and high-performance photonic devices drives the development of optical resonators with nanoscale sizes and ultrahigh quality factors. Fabry-Pérot (FP) resonators, the most widely employed optical resonators, can support ultrahigh quality factors in the simple structure, which is particularly attractive for applications in lasers, filters, and ultrasensitive sensors. However, the construction of FP resonators with both nanoscale sizes and high quality factors has still faced challenges. Herein we demonstrate the construction of FP nanoresonators out of single Au nanodisks (NDs) and a Au film, with a WS2 flake sandwiched in between. The atomically flat surfaces of the WS2 flake and Au NDs benefit mirror alignment and boost the quality factor up to 76. The nanoresonators can support FP resonances with different mode orders in the visible region. The optical properties and formation mechanisms of the high-quality FP modes are systematically studied. The FP modes are further hybridized with excitons in the WS2 flake spacer, enabling the modulation of the WS2 indirect band gap emissions. Our study combines the advantages of plasmonic nanoparticles and FP resonators, providing a promising platform for the development of compact nanophotonic devices such as tunable nanolasers, smart sensors, and photonic-circuit elements.

Signatures of Thalamocortical Alpha Oscillations and Synchronization With Increased Anesthetic Depths Under Isoflurane.

Background: Electroencephalography (EEG) recordings under propofol exhibit an increase in slow and alpha oscillation power and dose-dependent phase-amplitude coupling (PAC), which underlie GABAA potentiation and the central role of thalamocortical entrainment. However, the exact EEG signatures elicited by volatile anesthetics and the possible neurophysiological mechanisms remain unclear. Methods: Cortical EEG signals and thalamic local field potential (LFP) were recorded in a mouse model to detect EEG signatures induced by 0.9%, 1.5%, and 2.0% isoflurane. Then, the power of the EEG spectrum, thalamocortical coherence, and slow-alpha phase-amplitude coupling were analyzed. A computational model based on the thalamic network was used to determine the primary neurophysiological mechanisms of alpha spiking of thalamocortical neurons under isoflurane anesthesia. Results: Isoflurane at 0.9% (light anesthesia) increased the power of slow and delta oscillations both in cortical EEG and in thalamic LFP. Isoflurane at 1.5% (surgery anesthesia) increased the power of alpha oscillations both in cortical EEG and in thalamic LFP. Isoflurane at 2% (deep anesthesia) further increased the power of cortical alpha oscillations, while thalamic alpha oscillations were unchanged. Thalamocortical coherence of alpha oscillation only exhibited a significant increase under 1.5% isoflurane. Isoflurane-induced PAC modulation remained unchanged throughout under various concentrations of isoflurane. By adjusting the parameters in the computational model, isoflurane-induced alpha spiking in thalamocortical neurons was simulated, which revealed the potential molecular targets and the thalamic network involved in isoflurane-induced alpha spiking in thalamocortical neurons. Conclusion: The EEG changes in the cortical alpha oscillation, thalamocortical coherence, and slow-alpha PAC may provide neurophysiological signatures for monitoring isoflurane anesthesia at various depths.

Controlling and Focusing In-Plane Hyperbolic Phonon Polaritons in α-MoO3 with a Curved Plasmonic Antenna.

Hyperbolic phonon polaritons (HPhPs) sustained in polar van der Waals (vdW) crystals exhibit extraordinary confinement of long-wave electromagnetic fields to the deep subwavelength scale. In stark contrast to uniaxial vdW hyperbolic materials, recently emerged biaxial hyperbolic materials, such as α-MoO3 and α-V2 O5 , offer new degrees of freedom for controlling light in two-dimensions due to their distinctive in-plane hyperbolic dispersions. However, the control and focusing of these in-plane HPhPs remain elusive. Here, a versatile technique is proposed for launching, controlling, and focusing in-plane HPhPs in α-MoO3 with geometrically designed curved gold plasmonic antennas. It is found that the subwavelength manipulation and focusing behaviors are strongly dependent on the curvature of the antenna extremity. This strategy operates effectively in a broadband spectral region. These findings not only provide fundamental insights into the manipulation of light by biaxial hyperbolic crystals at the nanoscale but also open up new opportunities for planar nanophotonic applications.

Efficacy of Nalbuphine as a Local Anesthetic Adjuvant for Brachial Plexus Block: A Systematic Review and Meta-analysis.

BACKGROUND: Nalbuphine has been increasingly used as a local anesthetic adjuvant to extend the duration of analgesia in brachial plexus block (BPB). OBJECTIVES: To systematically and firstly evaluate the available evidence on the efficacy of nalbuphine as an adjuvant to local anesthetics in BPB. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Cochrane Central Register of Controlled Clinical Trials, Cochrane Database of Systematic Reviews, Medline, Embase, Scopus, Web of Science, EBSCO, PubMed, and additional databases were searched. Randomized controlled trials comparing combination of perineural nalbuphine with local anesthetics to local anesthetics alone in BPB for upper extremity surgical procedures were eligible for inclusion. RESULTS: Nineteen randomized controlled trials involving 1,355 patients met the inclusion criteria. Perineural use of nalbuphine prolonged the duration of analgesia in BPB (mean difference [MD], 162.5; 95% confidence interval [CI], 119.0 to 205.9; P < 0.00001; very low quality of evidence). The duration of sensory block was also extended (MD, 141.6; 95% CI, 100.3 to 182.9; P < 0.00001; very low quality of evidence). Furthermore, nalbuphine shortened the onset time of sensory block (MD, -2.6; 95% CI, -3.6 to -1.5; P < 0.00001; very low quality of evidence). There were no significant differences in side effect-related outcomes, including nausea (risk radio [RR], 1.56; 95% CI, 0.82 to 2.59; P = 0.17; moderate quality of evidence) and vomiting (RR, 1.41; 95%  CI, 0.66 to 3.02; P = 0.38; moderate quality of evidence). LIMITATIONS: The study was limited by substantial heterogeneity, a relatively small sample size and difference-in-differences in how outcomes of interest were described and assessed. CONCLUSIONS: Perineural use of nalbuphine in BPB is an effective strategy for analgesia in adult patients undergoing upper extremity surgery.

Effects of Perioperative Epidural Analgesia on Cancer Recurrence and Survival.

Surgical resection is the main curative avenue for various cancers. Unfortunately, cancer recurrence following surgery is commonly seen, and typically results in refractory disease and death. Currently, there is no consensus whether perioperative epidural analgesia (EA), including intraoperative and postoperative epidural analgesia, is beneficial or harmful on cancer recurrence and survival. Although controversial, mounting evidence from both clinical and animal studies have reported perioperative EA can improve cancer recurrence and survival via many aspects, including modulating the immune/inflammation response and reducing the use of anesthetic agents like inhalation anesthetics and opioids, which are independent risk factors for cancer recurrence. However, these results depend on the cancer types, cancer staging, patients age, opioids use, and the duration of follow-up. This review will summarize the effects of perioperative EA on the oncological outcomes of patients after cancer surgery.

Phonon Polaritons in Twisted Double-Layers of Hyperbolic van der Waals Crystals.

Controlling the twist angle between two stacked van der Waals (vdW) crystals is a powerful approach for tuning their electronic and photonic properties. Hyperbolic media have recently attracted much attention due to their ability to tailor electromagnetic waves at the subwavelength-scale which, however, usually requires complex patterning procedures. Here, we demonstrate a lithography-free approach for manipulating the hyperbolicity by harnessing the twist-dependent coupling of phonon polaritons in double-layers of vdW α-MoO3, a naturally biaxial hyperbolic crystal. The polariton isofrequency contours can be modified due to this interlayer coupling, allowing for controlling the polaritonic characteristics by adjusting the orientation angles between the two layers. Our findings provide opportunities for control of nanoscale light flow with twisted stacks of vdW crystals.

Potential use of C-phycocyanin in non-alcoholic fatty liver disease.

C-phycocyanin (C-PC) is a kind of photosynthetically assisted pigment, which is ubiquitous in cyanobacteria cells. We investigated the effect of C-PC on non-alcoholic fatty liver disease (NAFLD) and its mechanism. Through oil red O staining, TC/TG detection, liver SOD/MDA detection and liver H&E staining, we found that C-PC could significantly reduce the lipid accumulation in the steatosis L02 cells and the liver of non-alcoholic steatohepatitis (NASH) mice, and improve the antioxidant capacity of liver. The results of Western Blotting showed that C-PC upregulated the expression of AMPK phosphorylation and downregulated SREBP-1c and its target genes ACC and FAS expression levels. Furthermore, C-PC also upregulated the expression of transcription factor PPARα, which was regulated by AMPK, and its target genes CPT1 level. In addition, C-PC could promote AMPK phosphorylation in hepatocytes while increasing the phosphorylation level of ACC in vivo and in vitro. Besides, C-PC could also improve the liver inflammatory infiltration by upregulated the expression of PPARγ and downregulated the expression of CD36, IL6 and TNFα. These results indicate that C-PC may improve hepatic lipid accumulation and inflammation in the non-alcoholic fatty liver mice by activating AMPK pathway of hepatocytes. The finding provides important help for the research and development of C-PC in the nutraceuticals and therapeutics of NAFLD.