Gut dysbacteriosis induces expression differences in the adult head transcriptome of Spodoptera frugiperda in a sex-specific manner.

Mounting evidence indicates that the gut microbiota influences the neurodevelopment and behavior of insects through the gut-brain axis. However, it is currently unclear whether the gut microbiota affect the head profiles and immune pathway in pests. Here, we find that gut bacteria is essential for the immune and neural development of adult Spodoptera frugiperda, which is an extremely destructive agricultural pest worldwide. 16 S rRNA sequencing analysis showed that antibiotics exposure significantly disturbed the composition and diversity of gut bacteria. Further transcriptomic analysis revealed that the adult head transcripts were greatly affected by gut dysbacteriosis, and differently expression genes critical for brain and neural development including A4galt, Tret1, nsun4, Galt, Mitofilin, SLC2A3, snk, GABRB3, Oamb and SLC6A1 were substantially repressed. Interestingly, the dysbacteriosis caused sex-specific differences in immune response. The mRNA levels of pll (serine/threonine protein kinase Pelle), PGRP (peptidoglycan-sensing receptor), CECA (cecropin A) and CECB (cecropin B) involved in Toll and Imd signaling pathway were drastically decreased in treated male adults' heads but not in female adults; however, genes of HIVEP2, ZNF131, inducible zinc finger protein 1-like and zinc finger protein 99-like encoding zinc-finger antiviral protein (ZAP) involved in the interferon (IFNα/ß) pathway were significantly inhibited in treated female adults' heads. Collectively, these results demonstrate that gut microbiota may regulate head transcription and impact the S. frugiperda adults' heads through the immune pathway in a sex-specific manner. Our finding highlights the relationship between the gut microbiota and head immune systems of S. frugiperda adults, which is an astonishing similarity with the discoveries of other animals. Therefore, this is the basis for further research to understand the interactions between hosts and microorganisms via the gut-brain axis in S. frugiperda and other insects.

Abnormalities in the SIRT1-SIRT3 axis promote myocardial ischemia-reperfusion injury through ferroptosis caused by silencing the PINK1/Parkin signaling pathway.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is one of the main reasons for poor prognosis in patients with ischemic cardiomyopathy (ICM). To date, the mechanism remains unknown. As members of the silent information regulator 2 (SIR2) family, both SIRT1 and SIRT3 have been shown to play critical roles in protecting cardiomyocytes against MIRI, but their specific protective mechanism, their interact between the two and their relationship with ferroptosis are still unclear. Hence, in this study, we investigated the interact and specific mechanism of SIRT1 and SIRT3 in protecting cardiomyocytes against MIRI, as well as their association with ferroptosis. METHODS: Bioinformatics analysis methods were used to explore the expression of SIRT1 and SIRT3 during MIRI, and then a cell hypoxia/reoxygenation injury model was constructed to verify the results. Then, Pearson correlation analysis was further used to explore the relationship between SIRT1 and SIRT3, whose roles in the regulation of ferroptosis were also analysed by gene knock down, Western Blotting and flow cytometry. Several biomarkers, such as Fe2+ concentration, lipid peroxidation marker MDA and mitochondrial membrane potential (MMP), were used to evaluate changes in ferroptosis. RESULTS: The expression of SIRT1 and SIRT3 was abnormal during MIRI, and SIRT1 was significantly negatively correlated with SIRT3 in the SIRT1-SIRT3 axis. Further analysis revealed that the SIRT1-SIRT3 axis was closely correlated with ferroptosis, and its silencing effectively increase the incidence of ferroptosis. Furthermore, SIRT1-SIRT3 axis silencing was accompanied by changes in PINK1, Parkin, P62/SQSTM1 and LC3 expression. PINK1 silencing significantly increased the incidence of ferroptosis, while resveratrol (Res) and/or honokiol (HKL) effectively reversed the outcome. CONCLUSION: Abnormalities in the SIRT1-SIRT3 axis promote MIRI through ferroptosis caused by silencing the PINK1/Parkin signaling pathway.

Comprehensive analysis of the prognostic implications and functional exploration of PAK gene family in human cancer.

BACKGROUND: The p21-activated kinase (PAK) family (PAKs) plays a key role in the formation and development of human tumors. However, a systematic analysis of PAKs in human cancers is lacking and the potential role of PAKs in cancer immunity has not been explored. METHODS: We used datasets from in The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression database (GTEx). RESULTS: Based on TCGA datasets most PAKs show noteworthy differences in expression between tumors and corresponding normal tissues or across different tumor tissues. Patients with high expression of PAKs often show a worse prognosis. However, copy number variation, mutation, and DNA methylation of PAKs have limited impact on tumor development. Further analysis showed that the impact of PAKs on immunity varies with the type of tumor and the respective tumor microenvironment. PAK1 and PAK4 may be stronger predictors of immune characteristics, and are more suitable as drugs and molecular therapeutic targets. Furthermore, Cox regression analysis revealed that a PAK gene signature could be used as an independent prognostic factor for lower grade glioma (LGG) and glioblastoma (GBM). Gene set enrichment analysis (GSEA) analysis indicated that PAK genes may affect the occurrence and development of GBM through the PI3K signaling pathway. Further experiments verified that PAK1 and AKT1 have a significant interaction in GBM cells, and inhibiting the overactivation of PAK1 can significantly inhibit the proliferation of GBM cells. CONCLUSIONS: Our study provides a rationale for further research on the prognostic and therapeutic potential of PAKs in human tumors.

Intrinsic immune evasion patterns predict temozolomide sensitivity and immunotherapy response in lower-grade gliomas.

BACKGROUND: Although intrinsic immune-evasion is important in cancer proliferation, metastasis and response to treatment, it is unclear whether intrinsic immune-evasion patterns of gliomas can aid in predicting clinical prognosis and determining treatment. METHODS: A total of 182 immune-evasion genes intrinsic to cancer were subjected to consensus clustering to identify immune-evasion patterns in 1421 patients with lower-grade glioma (LGG). The levels of each cancer hallmark were determined by the Gene Set Variant Analysis (GSVA) method, and immune cell infiltrations were quantified using two algorithms, the single-sample Gene Set Enrichment Analysis (ssGSEA) and the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) methods. IEVscore was determined by a method that combined univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression and principal component analysis (PCA). RESULTS: Transcriptional and genomic analysis showed that most immune evasion genes (IEVGs) were upregulated in LGGs, with aberrant expression driven by alterations in copy number variants (CNV). Based on the mRNA expression profiles of cancer-intrinsic IEVGs could be divided into three LGG subgroups with distinct prognosis, clinicopathological features and immune infiltrations. A combined scoring scheme designed to assess the immune-evasion levels of LGGs divided these 1421 patients into two subgroups that differed in IEVscores. LGG patients with low-IEVscore had a better prognosis, would be more likely to benefit from immune check-point inhibitors and would be more susceptible to temozolomide (TMZ) chemotherapy. CONCLUSION: Intrinsic immune evasion in the tumor microenvironment (TME) has a crucial effect on glioma formation. Quantitatively assessing the IEV scores of individual LGG patients could enhance knowledge about the intra-glioma microenvironment and lead to the development of individualized therapeutic strategies for patients with LGG.

Clinical application of polylactic acid/gelatin nanofibre membrane in hard-to-heal lower extremity venous ulcers.

OBJECTIVE: To evaluate the safety and effectiveness of polylactic acid/gelatin nanofibre membranes (PGNMs) in treating hard-to-heal lower extremity venous ulcer wounds. METHOD: In this prospective study, patients with venous leg ulcers (VLUs) were treated with PGNMs or standard of care. Wounds were assessed once a week until the wound was fully healed. RESULTS: The treatment group was comprised of 10 patients with VLUs, aged between 47-64 years, with an average age of 56.58±6.19 years. The wounds were located in the lower leg and/or ankle. Average wound area was 8.91±13.57cm2 (range: 1.5-52.5cm2). Average wound healing time was 18.75±16.36 days. Of the patients, nine (90%) rated their pain as lighter when removing the dressing, with an average pain value of 2.0±1.0 points. There was less secondary trauma to the wound surface, and less bleeding. At six months after the wound healing, the scar evaluation (using the Vancouver Scar Scale) result was 3.75±1.96 points. CONCLUSION: In this study, the PGNMs were safe and effective in treating hard-to-heal lower extremity VLUs.

Mosaic ring chromosome 18 in a Chinese child with epilepsy: a case report and review of the literature.

BACKGROUND: Ring chromosome 18 (r[18]) is a rare syndrome in which one or both ends of chromosome 18 are lost and the remaining chromosome rejoins to form ring-shaped figures. It is characterized by developmental delay/cognitive disability, facial dysmorphisms, and immunological problems. The phenotype associated with epilepsy is rare and has not yet been reported in China. METHODS: We report herein the case of a 12-year-old Chinese girl who presented with typical facial dysmorphisms, developmental delay, cognitive disability, hyperactivity, and epilepsy and discuss the clinical features of r(18) syndromes through comparison with previously described cases worldwide. RESULTS: We describe the characteristics of all seizures that have been reported in these cases and propose that the appearance of epilepsy in r(18) patients may be associated with the abnormality of chromosome karyotypes. Further studies are warranted to confirm this.

Promising Electrochemiluminescence from CuInS2/ZnS Nanocrystals/Hydrazine via Internal Cu(I)/Cu(II) Couple Cycling.

Screening a novel electrochemiluminescence (ECL) system is crucial to ECL evolution. Herein, an efficient ECL system with less interference and environmental concern under physiological condition is developed via a unique internal Cu(I)/Cu(II) couple cycling amplified strategy by employing the glutathione- and citrate-capped copper indium sulfide (CIS)/ZnS nanocrystals (NCs) as electrochemiluminophore and N2H4·H2O as co-reactant. CIS/ZnS NCs can be electrochemically injected with valence band (VB) hole at 0.46 and 0.87 V (vs Ag/AgCl), and then achieve the same hole-injected states by relocalizing VB holes with the Cu(I) species inside of CIS/ZnS NCs to form internal Cu(II) defects, while each N2H4·H2O molecule can be successively oxidized to two more reducing species N2H3• and N2H2 around 0.10 V, and inject conduction band (CB) electron onto CIS/ZnS NCs for triple times. The internal Cu(I)/Cu(II) couple cycling involved radiative-charge recombination between these VB hole and CB electron eventually enables two efficient near-infrared ECL processes (around 731 nm) at 0.55 and 0.87 V, in which each single nanocrystal may participate in multiple ECL reaction cycles to produce multiple photons for amplified ECL, similar to the tris(bipyridyl)ruthenium(III) based ECL system. The low-triggering-potential ECL process at 0.55 V can be utilized to selectively determine Cu(II) with a wide linear range from 10 and 1500 nM and a limit of detection of 5 nM (S/N = 3). This work presents a NCs engineering and co-reactant selecting combined strategy for further ECL evolution.

Preparation of tannin-immobilized gelatin/PVA nanofiber band for extraction of uranium (VI) from simulated seawater.

A novel gelatin/PVA composite nanofiber band loaded with bayberry tannin (GPNB-BT) was prepared by electrostatic spinning and crosslinking for extraction of uranium (VI) from simulated seawater. The influential factors of tannin loaded on the nanofiber band were investigated in detail. Surface morphology and fiber diameter of GPNB-BT were studied by Scanning Electron Microscopy (SEM). Functional groups of GPNB-BT were investigated by Fourier Transform Infrared Spectrometer (FTIR). The adsorption process and mechanism of uranium on GPNB-BT was characterized by Energy Dispersive X-ray (EDX) and X-ray Photoelectron Spectroscopy (XPS). The results revealed that the BT had been stably solidified on the GPNB. Compared with other tannin-immobilized membranes, the nano-network structure of GPNB-BT with 200-400 nm diameter of fibers can promote solidification of tannins and improve adsorption capacity of GPNB-BT for uranium. The maximum adsorption capacity of the GPNB-BT for uranium is 170 mg/g at the optimal pH of 5.5 in 80 mg/L of initial uranium concentration and 1.4 µg/g even at extremely low initial concentration of 3 µg/L in the simulated seawater for 24 h. The GPNB-BT with good hydraulic properties, floatability and adsorption capacity for uranium is expected to be widely used in separation and enrichment of uranium in seawater and radioactive waste water.

[Clinical features of anti-N-methyl-D-aspartate receptor encephalitis and the concomitant seizure].

OBJECTIVE: To investigate the clinical features, auxiliary examination and characteristics for anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis and its concomitant seizure.
 Methods: A total of 20 patients diagnosed as anti-NMDAR encephalitis were enrolled from January 2016 to September 2018 in Xiangya Hospital. The data including the clinical features, auxiliary examination, characteristics of seizure, treatment and prognosis were collected. The discharged patients were followed up for half a year.
 Results: The initial symptom in patients with anti-NMDAR encephalitis were mainly psychiatric symptom and seizure. Most of the EEG result were diffused slow waves. The mainly type of seizure in patients with anti-NMDAR encephalitis showed generalized tonic-clonic seizure. Patients occurred consciousness during the onset of the disease. MRI showed that patients with temporal lobe were more inclined to occur seizure than patients with anti-NMDAR encephalitis (P<0.05). After standardized treatment, 20 patients showed a significant improvement in modified Rankin Scale (mRS) scores and the seizure was under control within half a year. 
 Conclusion: Patients with temporal lobe affected in MRI should pay attention to the possibility of seizure occurrence. Anti-epileptic drugs and immunotherapy should be used promptly in patient with seizure. After standardized treatment, the prognosis of patients will be mostly good.

Promising Anodic Electrochemiluminescence of Nontoxic Core/Shell CuInS2/ZnS Nanocrystals in Aqueous Medium and Its Biosensing Potential.

Copper indium sulfide (CuInS2, CIS) nanocrystals (NCs) are a promising solution to the toxic issue of Cd- and Pb-based NCs. Herein, electrochemiluminescence (ECL) of CIS NCs in aqueous medium is investigated for the first time with l-glutathione and sodium citrate-stabilized water-soluble CIS/ZnS NCs as model. The CIS/ZnS NCs can be oxidized to hole-injected states via electrochemically injecting holes into valence band at 0.55 and 0.94 V (vs Ag/AgCl), respectively. The hole-injected state around 0.94 V can bring out efficient oxidative-reduction ECL with a similar color to Ru(bpy)32+ in the presence of tri- n-propylamine (TPrA) and enable CIS/ZnS NCs promising ECL tags with l-glutathione as linker for labeling. The ECL of CIS/ZnS NCs/TPrA can be utilized to determine vascular endothelial growth factor (VEGF) from 0.10 to 1000 pM with the limit of detection at 0.050 pM (S/N = 3). Although the hole-injected state around 0.55 V is generated ahead of oxidation of TPrA and fails to bring out coreactant ECL, annihilation ECL proves that both hole-injected states generated, at 0.55 and 0.94 V, can be involved in electrochemical redox-induced radiative charge transfer by directly stepping CIS/ZnS NCs from electron-injecting potential to hole-injecting potential. CIS/ZnS NCs are promising nontoxic electrochemiluminophores with lowered ECL triggering potential around 0.55 V for less electrochemical interference upon the development of coreactant.

Successful treatment of reflex epilepsy with praxis induction by stimulus avoidance only.

PURPOSE: Reflex epilepsy is a type of epilepsy with seizures that are consistently triggered by a specific stimulus. Zipai is a Chinese ancient card game which has been popular in Southern China for hundreds of years. We sought to report and characterize clinical features of patients with reflex epilepsy evoked by playing Zipai. METHODS: We collected and analyzed clinical data of patients with Zipai-induced epilepsy. Patients were regarded as having Zipai-induced epilepsy if they suffered at least two seizure attack during the course of playing Zipai. Prolonged electroencephalography (EEG) and brain magnetic resonance imaging (MRI) were applied to all patients. All patients were advised to avoid watching and playing Zipai games in daily life, instead of using antiepileptic drugs. The seizure outcome was assessed during outpatient visits and by telephone contact. RESULTS: Five patients were included in this study. No spontaneous seizures occurred in all five patients. No patients had experienced myoclonic and coexistent absences with generalized tonic-clonic seizures (GTCS). All patients had normal MRI and prolonged EEG findings. All patients were advised to avoid the Zipai game, and became seizure-free without medication during the follow-up period (mean 5.4 years, range 3.5-7 years). CONCLUSION: Zipai-induced epilepsy may be an unreported subtype form of reflex epilepsy with praxis induction. Nonpharmacological conservative treatment plays a significant role in the treatment of reflex epilepsy.

Spectrum-Resolved Dual-Color Electrochemiluminescence Immunoassay for Simultaneous Detection of Two Targets with Nanocrystals as Tags.

A spectrum-resolved dual-color electrochemiluminescence (ECL) immunoassay was designed and implemented to simultaneously detect carcinoembryonic antigen (CEA) and alpha fetoprotein (AFP) with CdTe (λmax = 776 nm) and CdSe (λmax = 550 nm) nanocrystals (NCs) as ECL tags. The CdTe and CdSe NCs were labeled with respective probe antibodies (Ab2) of CEA and AFP, respectively, and then immobilized onto the working electrode surface via sandwich-type immunoreactions. Both CdTe and CdSe NCs within the NCs immunocomplexes can be electrochemically reduced and simultaneously give off monochromatic ECL emissions in the near-infrared and greenish regions, respectively, when (NH4)2S2O8 was used as a cathodic ECL coreactant. The ECL spectra of the two surface-confined NCs were well separated and had no cross energy-transfer interactions, which made the dual-color immunoassay highly selective and sensitive toward respective target analytes. With the proposed ECL biosensor, CEA and AFP were simultaneously detected and quantified with an extremely low detection limit of 1 pg/mL for CEA and 10 fg/mL for AFP, respectively. This work demonstrated the probability of performing multianalyte assays via a spectrum-resolved ECL strategy with improved sensitivity and signal-to-noise ratio as compared to NCs-based fluorescent multianalyte assays.

MicroRNA in glutamate receptor-dependent neurological diseases.

Glutamate-mediated excitotoxicity is the major neuropathological process contributing to numerous neurological diseases. Recently, emerging evidence indicates that microRNAs (miRNAs) play essential roles in the pathophysiology of a wide range of neurological diseases. Notably, there have been significant developments in understanding the biogenesis of miRNAs, their regulatory mechanisms, and their potential as effective biomarkers and therapies. In the present review, we summarize the recent literature that highlights the versatile roles played by miRNAs in glutamate receptor (GluR)-dependent neurological diseases. Based on the reported studies to date, modulation of miRNAs could emerge as a promising therapeutic target for a variety of neurological diseases that were discussed in this review.

Hydrogen Peroxide Involved Anodic Charge Transfer and Electrochemiluminescence of All-Inorganic Halide Perovskite CsPbBr3 Nanocrystals in an Aqueous Medium.

Reactive oxygen species (ROS) involved anodic charge transfer and electrochemiluminescence (ECL) of all-inorganic halide perovskite CsPbBr3 nanocrystals (NCs) were investigated in an aqueous medium with hydrogen peroxide (H2O2) as the model. CsPbBr3 NCs could be electrochemically oxidized to positively charged states by injecting holes onto the highest occupied molecular orbitals and could be chemically reduced to negatively charged states by injecting electrons onto the lowest unoccupied molecular orbitals by ROS. The charge transfer between CsPbBr3 NCs of oxidative and reductive states could bring out monochromatic ECL with onset around +0.8 V, maximum emission around 519 nm, and a full width at half-maximum around 20 nm. H2O2 could selectively enhance the anodic ECL of CsPbBr3 NCs, which not only opened a way to design a bioprocess-involved photovoltaic device with CsPbBr3 NCs but also was promising for color-selective ECL biosensing.

Community-wide changes in intertaxonomic temporal co-occurrence resulting from phenological shifts.

Global climate change is known to affect the assembly of ecological communities by altering species' spatial distribution patterns, but little is known about how climate change may affect community assembly by changing species' temporal co-occurrence patterns, which is highly likely given the widely observed phenological shifts associated with climate change. Here, we analyzed a 29-year phenological data set comprising community-level information on the timing and span of temporal occurrence in 11 seasonally occurring animal taxon groups from 329 local meteorological observatories across China. We show that widespread shifts in phenology have resulted in community-wide changes in the temporal overlap between taxa that are dominated by extensions, and that these changes are largely due to taxa's altered span of temporal occurrence rather than the degree of synchrony in phenological shifts. Importantly, our findings also suggest that climate change may have led to less phenological mismatch than generally presumed, and that the context under which to discuss the ecological consequences of phenological shifts should be expanded beyond asynchronous shifts.

Differential Expression of Adenosine P1 Receptor ADORA1 and ADORA2A Associated with Glioma Development and Tumor-Associated Epilepsy.

Level of adenosine, an endogenous astrocyte-based neuromodulator, is primarily regulated by adenosine P1 receptors. This study assessed expression of adenosine P1 receptors, ADORA1 (adenosine A1 receptor) and ADORA2A (adenosine A2a receptor) and their association with glioma development and epilepsy in glioma patients. Expression of ADORA1/ADORA2A was assessed immunohistochemically in 65 surgically removed glioma tissue and 21 peri-tumor tissues and 8 cases of normal brain tissues obtained from hematoma patients with cerebral trauma. Immunofluorescence, Western blot, and qRT-PCR were also used to verify immunohistochemical data. Adenosine P1 receptor ADORA1 and ADORA2A proteins were localized in the cell membrane and cytoplasm and ADORA1/ADORA2A immunoreactivity was significantly stronger in glioma and peri-tumor tissues that contained infiltrating tumor cells than in normal brain tissues (p < 0.05). The World Health Organization (WHO) grade III gliomas expressed even higher level of ADORA1 and ADORA2A. Western blot and qRT-PCR confirmed immunohistochemical data. Moreover, higher levels of ADORA1 and ADORA2A expression occurred in high-grade gliomas, in which incidence of epilepsy were lower (p < 0.05). In contrast, a lower level of ADORA1/ADORA2A expression was found in peri-tumor tissues with tumor cell presence from patients with epilepsy compared to patients without epilepsy (p < 0.05). The data from the current study indicates that dysregulation in ADORA1/ADORA2A expression was associated with glioma development, whereas low level of ADORA1/ADORA2A expression could increase susceptibility of tumor-associated epilepsy.

Serotonergic agents act on 5-HT3 receptors in the brain to block seizure-induced respiratory arrest in the DBA/1 mouse model of SUDEP.

Drugs that enhance the action of serotonin (5-hydroxytrypamine, 5-HT), including several selective serotonin reuptake inhibitors (SSRIs), reduce susceptibility to seizure-induced respiratory arrest (S-IRA) that leads to death in the DBA/1 mouse model of sudden unexpected death in epilepsy (SUDEP). However, it is not clear if specific 5-HT receptors are important in the action of these drugs and whether the brain is the major site of action of these agents in this SUDEP model. The current study examined the actions of agents that affect the 5-HT3 receptor subtype on S-IRA and whether intracerebroventricular (ICV) microinjection of an SSRI would reduce S-IRA susceptibility in DBA/1 mice. The data indicate that systemic administration of SR 57227, a 5-HT3 agonist, was effective in blocking S-IRA in doses that did not block seizures, and the S-IRA blocking effect of the SSRI, fluoxetine, was abolished by coadministration of a 5-HT3 antagonist, ondansetron. Intracerebroventricular administration of fluoxetine in the present study was also able to block S-IRA without blocking seizures. These findings suggest that 5-HT3 receptors play an important role in the block of S-IRA by serotonergic agents, such as SSRIs, which is consistent with the abnormal expression of 5-HT3 receptors in the brainstem of DBA mice observed previously. Taken together, these data indicate that systemically administered serotonergic agents act, at least, in part, in the brain, to reduce S-IRA susceptibility in DBA/1 mice and that 5-HT3 receptors may be important to this effect.

Fluoxetine prevents respiratory arrest without enhancing ventilation in DBA/1 mice.

Sudden unexpected death in epilepsy (SUDEP) is a fatal epileptic event. DBA/1 mice are a relevant animal model for the study of SUDEP, as these mice exhibit seizure-induced respiratory arrest (S-IRA) leading to death, which has been observed in patients with witnessed SUDEP. Fluoxetine, a selective serotonin (5-hydroxytryptamine or 5-HT) reuptake inhibitor (SSRI), reduces S-IRA in DBA/1 mice. Given that DBA/1 mice with S-IRA can be resuscitated using a ventilator, we hypothesized that breathing stimulants can prevent S-IRA and that fluoxetine prevents S-IRA by enhancing ventilation in these mice. Spontaneous respiratory function in anesthetized or awake DBA/1 mice was examined using noninvasive plethysmography before and after administering fluoxetine or breathing stimulants, doxapram, and 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (PK-THPP). The effects of these drugs on S-IRA in DBA/1 mice were tested. As reported previously, systemic administration of fluoxetine reduced S-IRA in awake DBA/1 mice, but fluoxetine in anesthetized and awake DBA/1 mice did not increase basal ventilation or the ventilatory response to 7% CO2. Both doxapram and PK-THPP increased ventilation in room air and in air+7% CO2 in anesthetized DBA/1 mice. However, neither of the breathing stimulants reduced the incidence of S-IRA. Our studies confirm that fluoxetine reduces S-IRA in DBA/1 mice without enhancing basal ventilation in the absence of seizures. Although breathing stimulants increased ventilation in the absence of seizures, they were ineffective in reducing S-IRA, indicating that drug-induced increases in ventilation are insufficient to compensate for S-IRA in DBA/1 mice.

Acute encephalitis induced Kleine-Levin syndrome with episodic vertical gaze dysfunction during hypersomnia episodes.

Kleine-Levin syndrome (KLS) is a rare, recurring sleep disorder that easily ignored. Episodic upward-gaze palsy is an uncommon manifestation observed in patients of KLS, which further complicates this disorder. Although peripheral microbial infection have been recognized as most common triggers for KLS, the underlying pathophysiology of this disorder remains unclear. We reported an unique case of KLS elicited by acute encephalitis, which was confirmed by pleocytosis of cerebrospinal fluid (CSF) at the early stage. The CSF returned to normal over time while the attacks continued to recur frequently. Episodic upward-gaze palsy was observed during attacks and clinical symptoms were exacerbated following a subsequent COVID-19 infection. This report presents a classic KLS case with distinctive characteristics, which should facilitate more accurate and earlier diagnosis for clinicians. Furthermore, it provides a new perspective for understanding the pathogenesis of this rare disease.

Melatonin attenuates chronic sleep deprivation-induced cognitive deficits and HDAC3-Bmal1/clock interruption.

BACKGROUND AND AIMS: Sleep is predicted as a key modulator of cognition, but the underlying mechanisms are poorly understood. In this study, we investigated the effects of melatonin on chronic rapid eye movement sleep deprivation (CRSD)-induced cognitive impairment and circadian dysfunction in rat models. METHODS: Thirty-six Sprague-Dawley male rats were divided into three groups: CRSD with saline treatment, CRSD with chronic melatonin injection (20 mg/kg/day), and non-sleep-deprived control. The cognitive behavioral tests as well as the expression of clocks and HDAC3 were evaluated in all groups. RESULTS: CRSD significantly reduced recognition index in novel object location, increased escape latency and distance traveling in Morris water maze while melatonin treatment attenuated CRSD-induced hippocampal-dependent spatial learning and memory deficits. Furthermore, the mRNAs of brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1(Bmal1) and circadian locomotor output cycles kaput (Clock) were globally down-regulated by CRSD with constant intrinsic oscillation in both hippocampus and peripheral blood. The protein levels of hippocampal Bmal1, Clock, and HDAC3 were also remarkably down-regulated following CRSD. Melatonin treatment reversed CRSD-induced alterations of Bmal1/Clock and HDAC3 on both mRNA levels and protein levels. CONCLUSIONS: Our data indicate that melatonin treatment attenuates CRSD-induced cognitive impairment via regulating HDAC3-Bmal1/Clock interaction. These findings explore a broader understanding of the relationship between sleep and cognition and provide a potential new therapeutic target for cognitive impairment.