The crucial role of locus coeruleus noradrenergic neurons in the interaction between acute sleep disturbance and headache.

BACKGROUND: Both epidemiological and clinical studies have indicated that headache and sleep disturbances share a complex relationship. Although headache and sleep share common neurophysiological and anatomical foundations, the mechanism underlying their interaction remains poorly understood. The structures of the diencephalon and brainstem, particularly the locus coeruleus (LC), are the primary sites where the sleep and headache pathways intersect. To better understand the intricate nature of the relationship between headache and sleep, our study focused on investigating the role and function of noradrenergic neurons in the LC during acute headache and acute sleep disturbance. METHOD: To explore the relationship between acute headache and acute sleep disturbance, we primarily employed nitroglycerin (NTG)-induced migraine-like headache and acute sleep deprivation (ASD) models. Initially, we conducted experiments to confirm that ASD enhances headache and that acute headache can lead to acute sleep disturbance. Subsequently, we examined the separate roles of the LC in sleep and headache. We observed the effects of drug-induced activation and inhibition and chemogenetic manipulation of LC noradrenergic neurons on ASD-induced headache facilitation and acute headache-related sleep disturbance. This approach enabled us to demonstrate the bidirectional function of LC noradrenergic neurons. RESULTS: Our findings indicate that ASD facilitated the development of NTG-induced migraine-like headache, while acute headache affected sleep quality. Furthermore, activating the LC reduced the headache threshold and increased sleep latency, whereas inhibiting the LC had the opposite effect. Additional investigations demonstrated that activating LC noradrenergic neurons further intensified pain facilitation from ASD, while inhibiting these neurons reduced this pain facilitation. Moreover, activating LC noradrenergic neurons exacerbated the impact of acute headache on sleep quality, while inhibiting them alleviated this influence. CONCLUSION: The LC serves as a significant anatomical and functional region in the interaction between acute sleep disturbance and acute headache. The involvement of LC noradrenergic neurons is pivotal in facilitating headache triggered by ASD and influencing the effects of headache on sleep quality.

Dopaminergic Projections from the Hypothalamic A11 Nucleus to the Spinal Trigeminal Nucleus Are Involved in Bidirectional Migraine Modulation.

Clinical imaging studies have revealed that the hypothalamus is activated in migraine patients prior to the onset of and during headache and have also shown that the hypothalamus has increased functional connectivity with the spinal trigeminal nucleus. The dopaminergic system of the hypothalamus plays an important role, and the dopamine-rich A11 nucleus may play an important role in migraine pathogenesis. We used intraperitoneal injections of glyceryl trinitrate to establish a model of acute migraine attack and chronicity in mice, which was verified by photophobia experiments and von Frey experiments. We explored the A11 nucleus and its downstream pathway using immunohistochemical staining and neuronal tracing techniques. During acute migraine attack and chronification, c-fos expression in GABAergic neurons in the A11 nucleus was significantly increased, and inhibition of DA neurons was achieved by binding to GABA A-type receptors on the surface of dopaminergic neurons in the A11 nucleus. However, the expression of tyrosine hydroxylase and glutamic acid decarboxylase proteins in the A11 nucleus of the hypothalamus did not change significantly. Specific destruction of dopaminergic neurons in the A11 nucleus of mice resulted in severe nociceptive sensitization and photophobic behavior. The expression levels of the D1 dopamine receptor and D2 dopamine receptor in the caudal part of the spinal trigeminal nucleus candalis of the chronic migraine model were increased. Skin nociceptive sensitization of mice was slowed by activation of the D2 dopamine receptor in SP5C, and activation of the D1 dopamine receptor reversed this behavioral change. GABAergic neurons in the A11 nucleus were activated and exerted postsynaptic inhibitory effects, which led to a decrease in the amount of DA secreted by the A11 nucleus in the spinal trigeminal nucleus candalis. The reduced DA bound preferentially to the D2 dopamine receptor, thus exerting a defensive effect against headache.

ACT001 Relieves NMOSD Symptoms by Reducing Astrocyte Damage with an Autoimmune Antibody.

Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory demyelinating disease, the pathogenesis of which involves autoantibodies targeting the extracellular epitopes of aquaporin-4 on astrocytes. We neutralized the AQP4-IgG from NMOSD patient sera using synthesized AQP4 extracellular epitope peptides and found that the severe cytotoxicity produced by aquaporin-4 immunoglobin (AQP4-IgG) could be blocked by AQP4 extracellular mimotope peptides of Loop A and Loop C in astrocyte protection and animal models. ACT001, a natural compound derivative, has shown anti-tumor activity in various cancers. In our study, the central nervous system anti-inflammatory effect of ACT001 was investigated. The results demonstrated the superior astrocyte protection activity of ACT001 at 10 µM. Furthermore, ACT001 decreases the behavioral score in the mouse NMOSD model, which was not inferior to Methylprednisolone Sodium Succinate, the first-line therapy of NMOSD in clinical practice. In summary, our study showed that astrocytes are protected by specific peptides, or small molecular drugs, which is a new strategy for the treatment of NMOSD. It is possible for ACT001 to be a promising therapy for NMOSD.

Ligand Engineering Enables Efficient Pure Red Tin-Based Perovskite Light-Emitting Diodes.

With increasing ecological and environmental concerns, tin (Sn)-based perovskite light-emitting diodes (PeLEDs) are competitive candidates for future displays because of their environmental friendliness, excellent photoelectric properties, and low-cost solution-processed fabrication. Nonetheless, their electroluminescence (EL) performance still lags behind that of lead (Pb)-based PeLEDs due to the fast crystallization rate of Sn-based perovskite films and undesired oxidation from Sn2+ to Sn4+ , leading to poor film morphology and coverage, as well as high density defects. Here, we propose a ligand engineering strategy to construct high-quality phenethylammonium tin iodide (PEA2 SnI4 ) perovskite films by using L-glutathione reduced (GSH) as surface ligands toward efficient pure red PEA2 SnI4 -based PeLEDs. We show that the hydrogen-bond and coordinate interactions between GSH and PEA2 SnI4 effectively reduce the crystallization rate of the perovskites and suppress the oxidation of Sn2+ and formation of defects. The improved pure red perovskite films not only show excellent uniformity, density, and coverage but also exhibit enhanced optical properties and stability. Finally, state-of-the-art pure red PeLEDs achieve a record external quantum efficiency of 9.32 % in the field of PEA2 SnI4 -based devices. This work demonstrates that ligand engineering represents a feasible route to enhance the EL performance of Sn-based PeLEDs.

Porous activated carbons derived from bamboo pulp black liquor for effective adsorption removal of tetracycline hydrochloride and malachite green from water.

As a kind of wastewater produced by papermaking industry, bamboo pulp black liquor (BPBL) discharged into water causes serious environmental problems. In this work, BPBL was successfully converted into porous carbon after activation with potassium hydroxide (KOH) through one-step carbonization, and adsorption properties of porous carbon derived from bamboo pulp black liquor (BLPC) for tetracycline hydrochloride (TCH) and malachite green (MG) were studied. The adsorption capacities of BLPC for TCH and MG are 1047 and 1277 mg/g, respectively, due to its large specific surface area of 1859.08 m2/g. Kinetics and isotherm data are well fitted to the pseudo-second-order rate model and Langmuir model, respectively. Adsorption experiments and characterizations reveal that the adsorption mechanism involved in TCH and MG adsorption on BLPC mainly depends on the synergistic effect of pore filling, H-bonding, π-π interactions and weak electrostatic interactions. In addition, BLPC shows excellent photothermal properties, and the adsorption capacity of TCH and MG on BLPC can reach 584 and 847 mg/g under the irradiation of near infrared lamp for 50 min, respectively. The synthesized BLPC with high adsorption efficiency, good recovery ability, improved adsorption under near-infrared irradiation can be a promising and effective adsorbent for TCH or MG or other pollutes.

Repeated inflammatory dural stimulation-induced cephalic allodynia causes alteration of gut microbial composition in rats.

BACKGROUND: Gut microbial dysbiosis and gut-brain axis dysfunction have been implicated in the pathophysiology of migraine. However, it is unclear whether migraine-related cephalic allodynia could induce the alteration of gut microbial composition. METHODS: A classic migraine rat model was established by repeated dural infusions of inflammatory soup (IS). Periorbital mechanical threshold and nociception-related behaviors were used to evaluate IS-induced cephalic allodynia and the preventive effect of topiramate. The alterations in gut microbial composition and potential metabolic pathways were investigated based on the results of 16 S rRNA gene sequencing. Microbiota-related short-chain fatty acids and tryptophan metabolites were detected and quantified by mass spectrometry analysis. RESULTS: Repeated dural IS infusions induced cephalic allodynia (decreased mechanical threshold), migraine-like behaviors (increased immobility time and reduced moving distance), and microbial composition alteration, which were ameliorated by the treatment of topiramate. Decreased Lactobacillus was the most prominent biomarker genus in the IS-induced alteration of microbial composition. Additionally, IS infusions also enhanced metabolic pathways of the gut microbiota in butanoate, propanoate, and tryptophan, while the increased tryptophan-related metabolites indole-3-acetamide and tryptophol in feces could be the indicators. CONCLUSIONS: Inflammatory dural stimulation-induced cephalic allodynia causes the alterations of gut microbiota profile and microbial metabolic pathways.

Perovskite Light-Emitting Diodes with an External Quantum Efficiency Exceeding 30.

Perovskite light-emitting diodes (PeLEDs) are strong candidates for next-generation display and lighting technologies due to their high color purity and low-cost solution-processed fabrication. However, PeLEDs are not superior to commercial organic light-emitting diodes (OLEDs) in efficiency, as some key parameters affecting their efficiency, such as the charge carrier transport and light outcoupling efficiency, are usually overlooked and not well optimized. Here, ultrahigh-efficiency green PeLEDs are reported with quantum efficiencies surpassing a milestone of 30% by regulating the charge carrier transport and near-field light distribution to reduce electron leakage and achieve a high light outcoupling efficiency of 41.82%. Ni0.9 Mg0.1 Ox films are applied with a high refractive index and increased hole carrier mobility as the hole injection layer to balance the charge carrier injection and insert the polyethylene glycol layer between the hole transport layer and the perovskite emissive layer to block the electron leakage and reduce the photon loss. Therefore, with the modified structure, the state-of-the-art green PeLEDs achieve a world record external quantum efficiency of 30.84% (average =  29.05 ± 0.77%) at a luminance of 6514 cd m-2 . This study provides an interesting idea to construct super high-efficiency PeLEDs by balancing the electron-hole recombination and enhancing the light outcoupling.

Constructing Perovskite/Polymer Core/Shell Nanocrystals with Simultaneous High Efficiency and Stability for Mini-LED Backlights.

Lead halide perovskite nanocrystals (NCs) have been the star material in lighting and displays owing to their excellent photoelectrical properties, but they have not simultaneously realized high photoluminescence quantum yield (PLQY) and high stability. To solve this problem, we propose a perovskite/linear low-density polyethylene (perovskite/LLDPE) core/shell NC by the synergistic role of the pressure effect and steric effect. Green CsPbBr3/LLDPE core/shell NCs with near-unity PLQY and nonblinking behavior were synthesized through an in situ hot-injection process. The mechanism of the improved photoluminescence (PL) properties is the enhanced pressure effect resulting in increased radiative recombination and interaction between the ligand and perovskite crystals, as confirmed by the PL spectra and finite element calculations. Meanwhile, the NCs show high stability under ambient conditions (with a PLQY of 92.5% after 166 days) and against 365 nm UV light (maintaining 61.74% of the initial PL intensity after continuous radiation for 1000 min). This strategy also works well in the blue and red perovskite/LLDPE NCs and red InP/ZnSeS/ZnS/LLDPE NCs. Finally, white-emitting Mini-LEDs were fabricated by combining the green CsPbBr3/LLDPE and red CsPbBr1.2I1.8/LLDPE core/shell NCs with blue Mini-LED chips. The white-emitting Mini-LEDs exhibit super wide color gamut (∼129% of the National Television Standards Committee or 97% of the Rec. 2020 standards).

Bamboo cellulose-derived activated carbon aerogel with controllable mesoporous structure as an effective adsorbent for tetracycline hydrochloride.

Activated carbon has been widespread applied in the removal of pollutants in wastewater. However, many biomass-derived activated carbon suffer from the challenge of controllable pore size regulation, hindering their efficient adsorption of pollutants. Herein, bamboo-derived activated carbon aerogel (BACA) has been successfully prepared through KOH high-temperature activation of cellulose aerogel which was prepared using cellulose extracted from bamboo. Bamboo cellulose aerogel provides sufficient reaction sites for KOH, which is conducive to the formation of a mass of mesoporous structures on the pore walls of the activated carbon aerogel. The optimal BACA adsorbent shows high specific surface area (2503.80 m2/g), and maximum adsorption capability for tetracycline hydrochloride (TCH) reaches 863.8 mg/g at 30 ℃. The removal efficiencies of TCH are 100% and 98.4% at 40 ℃ when the initial concentrations are 500 and 700 mg/L, respectively. Adsorption kinetics and isotherm indicate that the adsorption of BACA for TCH is monolayer adsorption based on chemical adsorption. Spontaneous and endothermic adsorption processes are proved by adsorption thermodynamic studies. Additionally, coexisting ions have insignificant effect on TCH adsorption, and the BACA sample displays excellent adsorption property for five reuse cycles with a removal efficiency of 80.95%, indicating the outstanding adsorption capacity of BACA in practical application. The excellent adsorption performance provides BACA with a promising perspective to remove TCH from wastewater, and the prepared method of BACA can be widely extended to other biomass materials.

A Bibliometric and Scientific Knowledge Map Study of Migraine Treatment from 2013 to 2022.

Background: Migraine treatment research has made much great progress over the past decade. However, there have been few bibliometric studies conducted so far. In this study, bibliometric analysis was used to explore the current status and future trends of migraine treatment research. Methods: Migraine treatment-related articles were retrieved from the Web of Science Core Collection on December 7, 2022. Quantitative variables were analyzed by the R-tool bibliometrix and Excel 2020. VOS viewer and CiteSpace software were used to visualize citation, co-authorship, co-occurrence, and co-citation analysis of countries/regions, organizations, authors, references, and keywords. Results: A total of 3294 articles were included with the global publication output showing a slow upward trend. The United States was the most productive country with 1116 papers and gained the most citations. Albert Einstein College of Medicine was the most active institution with 176 papers. Headache published the most articles in this domain, while Cephalalgia was the most commonly co-cited journal. Lipton, RB published the most articles and had the most citations. Tepper S, 2017, Lancet neurology and Silberstein S, 2004, Cephalalgia were defined as classic articles. The current research mainly focuses on CGRP-related therapeutics, such as fremanezumab, erenumab and ubrogepant. Conclusion: Based on the analysis of bibliometric data on migraine treatment over the past decade, the trends and the knowledge graph of the country, organization, author, reference, and the keyword were identified, providing accurate and quick positioning of the critical information in the domain.

Upregulation of C-X-C motif chemokine 12 in the spinal cord alleviated the symptoms of experimental autoimmune encephalomyelitis in Lewis rats.

Background: C-X-C motif chemokine 12 (CXCL12) is a chemokine that performs many functions. Studies have shown that CXCL12 can aggravate inflammatory symptoms in the central nervous system (CNS). Evidence also indicates that CXCL12 can promote the repair of myelin sheaths in the CNS in experimental autoimmune encephalomyelitis (EAE). Here, we investigated the function of CXCL12 in CNS inflammation by upregulating CXCL12 in the spinal cord and subsequently inducing EAE. Materials and methods: CXCL12 upregulation in the spinal cords of Lewis rats was induced by the injection of adeno-associated virus 9 (AAV9)/eGFP-P2A-CXCL12 after intrathecal catheter implantation. Twenty-one days after AAV injection, EAE was induced and clinical score was collected; Immunofluorescence staining, WB and LFB-PAS staining were used to evaluate the effect of CXCL12 upregulation. In the in vitro study, oligodendrocyte precursor cells (OPCs) were harvested, cultured with CXCL12 and AMD3100, and subjected to immunofluorescence staining for functional assessment. Results: CXCL12 was upregulated in the lumbar enlargement of the spinal cord by AAV injection. In each stage of EAE, upregulation of CXCL12 significantly alleviated clinical scores by inhibiting leukocyte infiltration and promoting remyelination. In contrast, the addition of AMD3100, which is a CXCR4 antagonist, inhibited the effect of CXCL12. In vitro, 10 ng/ml CXCL12 promoted the differentiation of OPCs into oligodendrocytes. Conclusion: AAV-mediated upregulation of CXCL12 in the CNS can alleviate the clinical signs and symptoms of EAE and significantly decrease the infiltration of leukocytes in the peak stage of EAE. CXCL12 can promote the maturation and differentiation of OPCs into oligodendrocytes in vitro. These data indicate that CXCL12 effectively promotes remyelination in the spinal cord and decreases the signs and symptoms of EAE.

Clinical Characteristics of Methanol-Induced Optic Neuropathy: Correlation between Aetiology and Clinical Findings.

Purpose: To show the clinical characteristics, identify the magnetic resonance imaging (MRI) and optical coherence tomography (OCT) features, and observe the visual outcome of methanol-induced optic neuropathy. Methods: Clinical data were retrospectively collected from in-patients diagnosed with methanol-induced optic neuropathy in the Neuro-Ophthalmology Department of the Chinese People's Liberation Army General Hospital from January 2016 to January 2021. Results: Eight patients were included in this study. The exposure time was 6-34 h for ingestion, 3-4 months for inhalation, and more than ten years for skin absorption. All patients demonstrated bilateral acute visual impairment. Seven of eight patients had other accompanying systemic symptoms. Seven of eight patients demonstrated optic nerve lesions in MRI, and five presented with a hyperintense T2 signal in a "central" type. OCT showed the macular ganglion cell layer and inner plexiform layer (mGCL-IPL) thinning before the peripapillary retinal nerve fiber layer (pRNFL) thinning. The visual improvement was achieved transiently for seven of eight patients after treatment. One patient with a mitochondrial DNA mutation maintained a bilateral no-light perception (NLP) from the onset to the last visit. All patients had poor visual prognoses, with either light perception or NLP. Conclusions: Methanol-induced optic neuropathy is a rare bilateral optic neuropathy with a poor visual outcome. A centrally hyperintense T2 signal of the optic nerve is common in methanol-induced optic neuropathy. The thinning of the mGCL-IPL is more sensitive than that of the pRNFL for early diagnosis. A mitochondrial genetic defect may be a predisposing factor for methanol-induced optic neuropathy.

Shape-controlled silver nanoplates colored fabric with tunable colors, photothermal antibacterial and colorimetric detection of hydrogen sulfide.

Anisotropic silver nanoplates are widely anticipated in multifunctional textiles, but their large-scale promotion is limited by the shortcomings of long reaction time, uncontrollable shape and low yield in the preparation process. In this study, a microwave-assisted strategy is provided to prepare shape-controllable silver nanoplates for coloration of non-woven fabric. Anisotropic Ag nanoplates are efficiently coated on the surface of chitosan-pretreated fabric by a simple solution impregnation method, which generates the fabric with tunable color and multiple functions. The Ag nanoplates loaded fabric exhibits excellent photothermal properties at 808 nm laser irradiation due to its unique plasmonic absorption features. Colored fabric shows a strong synergistic antibacterial effect, including silver ion release and hyperthermia caused by the photothermal effect under near-infrared (NIR) light. Additionally, colored fabrics can be used as colorimetric sensors for selective detection of H2S. The colorimetric values of visible color signal of fabric-based H2S gas sensor can be real-time precisely detected using a smartphone, enlightening its high potential as a wearable toxic gas alarm device for the simple and rapid detection of hazardous gases.

Serial analyses of clinical spectra and outcomes in Chinese women with pregnancy-induced optic neuritis.

Objective: This study aimed to investigate the clinical spectra and outcomes in pregnancy-related optic neuritis (ON). Methods: We analyzed the clinical subtype and prognosis of women with pregnancy-related ON in the neuro-ophthalmology department of the First Medical Center at the Chinese PLA General Hospital from January 2014 to December 2019. Results: A total of 54 patients, including 21 (38.9%) with idiopathic ON (ION), 27 (50.0%) with aquaporin-4 (AQP4)-ON, and 6 (11.6%) with myelin oligodendrocyte glycoprotein (MOG)-ON, who experienced 58 informative pregnancies and 67 episodes of pregnancy-related ON were assessed. Among the ON attacks, there were 11 (16.4%) during pregnancy and 56 (83.6%) within 1 year postpartum (PP1) or after abortion, including 33 (49.3%) in the first trimester. In total, 14 (25.9%) patients with ON onset before pregnancy had a higher relapse rate during PP1 than within 1 year before pregnancy (p = 0.021), and 24 (85.7%) eyes with ION and nine (100%) with MOG-ON had significantly better visual outcomes (p ≥ 0.5) than those with AQP4-ON (14, 35%) (p < 0.001 and p < 0.001, respectively). Two AQP4-ON patients had premature birth and low baby weight, respectively. There were no birth defects or stillbirths. Conclusion: The significantly increased relapse rate and numerous cases of ON after pregnancy suggest that delivery adversely affects the course of ON.

In Situ Inkjet Printing Patterned Lead Halide Perovskite Quantum Dot Color Conversion Films by Using Cheap and Eco-Friendly Aqueous Inks.

Inkjet-printed perovskite quantum dot (PQD) color conversion films (CCFs) have great potentials for mini/micro-LED displays because of their ultrahigh color purity, tunable emissions, high efficiency, and high-resolution. However, current PQD inks mainly use expensive, toxic, and flammable organic substances as solvents. In this work, water is proposed to be used as the solvent for inkjet printing PQD/polymer CCFs. The green-emitting patterned MAPbBr3 /polyvinyl alcohol (PVA) films are in situ prepared by using halides and the PVA-based aqueous ink. The as-printed CCFs exhibit a high-resolution dot matrix of 90 µm with a bright green emission (λem  = 526 nm), a high photoluminescence quantum yield of 85%, and a narrow full width at half maximum of 22 nm. They have both air- and photo-stabilities under ambient conditions, and each pixel of CCFs is relatively uniform in morphology and fluorescence when the substrate temperature is 80 °C. The patterned blue-emitting MAPbClx Br3-x /PVA and red-emitting Cs0.3 MA0.7 PbBrx I3-x /PVA can also be printed by aqueous inks. These results indicate that the designed aqueous inks are promising for in situ inkjet printing high resolution and reliability PQD CCFs for mini/micro-LED displays.