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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 a unique case of KLS elicited by acute encephalitis, which was confirmed by pleocytosis of cerebrospinal fluid at the early stage. The cerebrospinal fluid 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., Citation: Lv H, Long X, Lv Y, Zhou J. Acute encephalitis induced Kleine-Levin syndrome with episodic vertical gaze dysfunction during hypersomnia episodes. J Clin Sleep Med . 2024;20(9):1555-1556., (© 2024 American Academy of Sleep Medicine.)

Spinel Li 4 Ti 5 O 12 (LTO), a zero-strain material, is a promising anode material for solid-state thin-film lithium-ion batteries (TFB). However, the preparation of high-performance Li 4 Ti 5 O 12 thin-film electrodes through facile methods remains a significant challenge. Herein, we present a novel approach to prepare a binder- and conductor-free porous Li 4 Ti 5 O 12 (P-LTO) thin-film. This approach polyvinyl alcohol (PVA)-assisted spray deposition and does not require the use of complex or expensive methods. Adding PVA to the precursor solution effectively prevents thin-film cracking during high-temperature annealing, enhances adhesion, and forms a highly interconnected porous structure. This unique structure shortens the lithium-ion diffusion pathways and facilitates electron transport. Therefore, P-LTO thin film electrodes demonstrate exceptional rate capacity of 104.1 mAh/g at a current density of 100C. In addition, the electrodes exhibit ultra-long cycle stability, retaining 80.9 % capacity after 10,000 cycles at 10C. This work offers a novel approach for the preparation of high-performance thin-film electrodes for TFBs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Study Objectives: To systemically describe the clinical features, polysomnography (PSG) finding, laboratory tests and single-nucleotide polymorphisms (SNPs) in a clinic based Chinese primary restless legs syndrome (RLS) population., Methods: This observational study, conducted from January 2020 to October 2021 across 22 sleep labs in China, recruited 771 patients diagnosed with RLS following the 2014 RLSSG criteria. Clinical data, PSG testing, and laboratory examination and SNPs of patients with RLS were collected. A total of 32 SNPs in 24 loci were replicated using the Asian Screening Array chip, employing data from the Han Chinese Genomes Initiative as controls., Results: In this study with 771 RLS patients, 645 had primary RLS, and 617 has DNA available for SNP study. Among the 645 primary RLS, 59.7% were women. 33% had a family history of RLS, with stronger familial influence in early-onset cases. Clinical evaluations showed 10.4% had discomfort in body parts other than legs. PSG showed that 57.1% of RLS patients had periodic leg movement index (PLMI) of >5/h and 39.1% had PLMI >15/h, respectively; 73.8% of RLS patients had an Apnea-Hypopnea Index (AHI) > 5/h, and 45.3% had an AHI >15/h. The laboratory examinations revealed serum ferritin levels <75 ng/ml in 31.6%, and transferrin saturation (TSAT) of <45% in 88.7% of RLS patients. Seven new SNPs in 5 genes showed a significant allelic association with Chinese primary RLS, with one previously reported (BTBD9) and four new findings (TOX3, PRMT6, DCDC2C, NOS1)., Conclusions: Chinese RLS patients has specific characters in many aspects. A high family history with RLS not only indicates strong genetic influence, but also reminds us to consider the familial effect in the epidemiological study. Newly developed sequencing technique with large samples remains to be done., Competing Interests: Declaration of competing interest Authors declare none., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Aqueous zinc-sodium hybrid batteries with a Prussian blue cathode have been extensively studied in recent years. However, less research has been conducted on low-cost ferric ferricyanide (FeFe(CN) 6 ) cathode materials. Considering that both Zn 2+ and Na + can be reversibly embedded in FeFe(CN) 6 crystals, here we focus on mixed electrolytes with different concentrations of ZnSO 4 and Na 2 SO 4 in deionized water to explore the preference of FeFe(CN) 6 towards Zn 2+ and Na + . As a result, by using 0.1 M ZnSO 4 + 1 M Na 2 SO 4 electrolyte, a superior battery performance is obtained, which reveals that the co-function of Zn 2+ and Na + in this electrolyte promotes Zn//FeFe(CN) 6 cells to exert a superior specific capacity. In this work, FeFe(CN) 6 is synthesized by a co-precipitation method and is analyzed by XRD, SEM, etc ., and then used as the cathode material in Zn-Na hybrid batteries. Cyclic voltammetry (CV) and galvanostatic charge-discharge (GCD) tests show that FeFe(CN) 6 in 0.1 M ZnSO 4 + 1 M Na 2 SO 4 electrolyte delivers the highest discharge/charge capacities of 165.2/165.9 mA h g -1 (theoretical specific capacity: 212.2 mA h g -1 ) at a 0.1 C current density, with good capacity retention of 84% after 200 cycles at 15 C, outperforming many of the reported Zn-Na hybrid cells.

The Ni-rich NCM622 is a promising cathode material for future high energy lithium ion batteries, but unstable electrochemical performance of NCM622 hinder its large scale commercial application. The cycling peformance of nickel-rich LiNi 0.6 Co 0.2 Mn 0.2 O 2 (NCM622) cathode materials can be improved by surface coating. Here, a one-step approach based on TiF 4 is used to successfully manufacture modified NCM622 cathode materials with a TiO 2 -LiF coating. The TiO 2 -LiF coated NCM622 preserves 79.7% capacity retention which is higher than the pure NCM622 (68.9%) at 1C after 200 cycles within 2.7-4.3 V. This material serves as the cathode for lithium-ion batteries (LIBs). The uniform TiO 2 -LiF coating layer can alleviate structural degradation brought on by unfavorable side reactions with the electrolyte has been validated. TiO 2 -LiF coated on NCM622 cathode materials can be modified easily by one-step approach., Competing Interests: There are no declared conflicts., (This journal is © The Royal Society of Chemistry.)

Objective: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons. The motor phenotypes of ALS are highly clinically heterogeneous, and the underlying mechanisms are poorly understood., Methods: A comparative proteomic analysis was performed in the cerebrospinal fluid (CSF) of bulbar-onset (BO) and spinal-onset (SO) ALS patients and controls (n = 14). Five biomarker candidates were selected from a differentially regulated protein pool, and further validation was performed in a larger independent cohort (n = 92) using enzyme-linked immunosorbent assay (ELISA)., Results: A total of 1732 CSF proteins were identified, and 78 differentially expressed proteins were found among BO-ALS patients, SO-ALS patients, and controls. Five promising biomarker candidates were selected for further validation, and lipopolysaccharide-binding protein (LBP) and HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA) were validated. CSF LBP levels were increased in ALS patients compared with controls and higher in BO-ALS versus SO-ALS. The increased CSF LBP levels were correlated with the revised ALS Functional Scale (ALSFRS-R) score. CSF HLA-DRA levels were specifically elevated in BO-ALS patients, and there was no significant difference between SO-ALS patients and controls. Increased HLA-DRA expression was correlated with decreased survival., Interpretation: Our data shows that elevated CSF LBP is a good biomarker for ALS and correlates with clinical severity, and increased HLA-DRA is a specific biomarker for BO-ALS and may predict short survival. It also suggests that the microglial pathway and HLA-II-related adaptive immunity may be differentially involved in ALS phenotypes and may be new therapeutic targets for ALS., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

The goal of this study was to demonstrate the functions and specific mechanism of long non-coding RNA (lncRNA) GNAS-AS1 in lung adenocarcinoma. Levels of lncRNA GNAS-AS1, microRNA (miR)-433-3p, and Rab3A were assessed by quantitative real-time PCR (qRT-PCR). The target-binding sites of lncRNA GNAS-AS1, miR-433-3p, and Rab3A were predicted and confirmed by bioinformatics tool (StarBase) and a dual-luciferase reporter system. Cell proliferation and apoptosis were checked using MTT and flow cytometry, respectively. Additionally, the levels of apoptosis-related and epithelial-mesenchymal transition (EMT)-associated genes in A549 cells were analyzed by qRT-PCR and western blot. We found that lncRNA GNAS-AS1 was upregulated, miR-433-3p was low-expressed, and Rab3A was overexpressed in lung adenocarcinoma tissues and cell lines. LncRNA GNAS-AS1 interacted with miR-433-3p and negatively regulated miR-433-3p levels. Rab3A was a direct target of miR-433-3p. Downregulation of lncRNA GNAS-AS1 remarkably suppressed cell proliferation, promoted cell apoptosis, decreased B-cell lymphoma-2 (Bcl-2) expression, enhanced the Bcl-2-Associated X (Bax) level, promoted E-cadherin expression, and reduced N-cadherin and Rab3A levels. However, the miR-433-3p inhibitor reversed all these findings. Similarly, the inhibitory effects of miR-433-3p mimic on A549 cells were reversed by the Rab3A-plasmid. In conclusion, lncRNA GNAS-AS1 downregulation suppressed lung adenocarcinoma cell proliferation and EMT through the miR-433-3p/Rab3A axis., Competing Interests: Conflict of interest: The authors declare that they have no competing interests., (© 2023 the author(s), published by De Gruyter.)

Objectives: Autoimmune encephalitis arising from autoantibodies against leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) are rare and with high clinical heterogeneity. They are easily misdiagnosed and missing diagnosed. This study aims to explore the clinical characteristics, auxiliary examinations, therapies and prognosis of anti-LGI1 and anti-CASPR2 encephalitis., Methods: Seventeen anti-LGI1 and 11 anti-CASPR2 encephalitis patients who were admitted to the Department of Neurology, Xiangya Hospital, Central South University between January 2018 and January 2021 were collected and retrospectively analyzed. Autoimmune encephalitis related antibodies and paraneoplastic antibodies were screened in all patients. The clinical manifestations, results of laboratory tests, imaging features, treatments and outcomes of 2 encephalitis groups were analyzed and compared., Results: In the anti-LGI1 encephalitis group, the age of 17 patients was 28-83 (53.18±19.08) years old, and the ratio of male to female was 9꞉8. There were 10 patients with cognitive impairment, 7 seizures, 4 faciobrachial dystonic seizures, and 1 psychiatric disturbance. Hyponatremia was observed in 7 patients. Eight patients had increased slow waves and 5 had epileptic discharge in electroencephalogram (EEG). Brain magnetic resonance (MRI) showed T 2 -weighted imaging (T 2 WI) and fluid attenuated inversion recovery (FLAIR) hyperintense signal in the temporal lobe, hippocampus and basal ganglia in 13 patients. In the anti-CASPR2 group, the age of 11 patients was 17-68 (47.18±16.20) years old, and the ratio of male to female was 5꞉6, with 7 limbic encephalitis, 1 Morvan syndrome, and 3 acquired neuromyotonia (NMT). Three patients had increased slow waves and 2 had epileptic discharge in EEG. Brain MRI showed T 2 WI and FLAIR hyperintense signal in the temporal lobe, hippocampus in 2 patients. Steroids, intravenous immunoglobin, and plasma exchange were administrated in 16 anti-LGI1 encephalitis and 8 anti-CASPR2 encephalitis patients with good therapeutic responses. Among them, 1 patient with anti-LGI1 encephalitis and 3 with anti-CASPR2 encephalitis were administrated with mycophenolate mofetil for immune maintenance therapy. No recurrences were observed in all patients with immunotherapy except for 2 patients who lost of follow-up. There were significant differences in cognitive impairment, hyponatremia, and brain MRI abnormalities between anti-LGI1 and anti-CASPR2 encephalitis patients (all P <0.05)., Conclusions: Limbic encephalitis is a common syndrome in both anti-LGI1 and anti-CASPR2 encephalitis patients. Anti-CASPR2 encephalitis has a wider clinical spectrum than anti-LGI1 encephalitis, presenting as NMT and Morvan syndrome, which has a closer relationship with tumors. Both of these 2 antibodies associated disorders are sensitive to immunotherapy and have a good prognosis.

Efficient biocoagulants/bioflocculants are desired for removal of Microcystis aeruginosa, the dominant harmful bloom-forming cyanobacterium. Herein, we reported cationic hydroxyethyl cellulose (CHEC) inactivated M. aeruginosa cells after forming coagulates and floating-flocculated them with aid of Agrobacterium mucopolysaccharides (AMP) and surfactant. CHEC exhibited cyanocidal activity at 20 mg/L, coagulating 85% of M. aeruginosa biomass within 9 h and decreasing 41% of chlorophyll a after 72 h. AMP acted as an adhesive flocculation aid that accelerated and strengthened the formation of flocs, approaching a maximum in 10 min. Flocs of M. aeruginosa were floated after foaming with cocoamidopropyl betaine (CAB), which facilitated the subsequent filter harvest. 82% of M. aeruginosa biomass was suspended on water surface after treated with the coagulation/flocculation-flotation (CFF) agents containing CHEC (25 mg/L), AMP (177 mg/L) and CAB (0.1 mg/L). All components in CFF agents at the applied concentrations did not inhibit acetylcholinesterase or Vibrio fischeri. Our findings provide new insights in developing bio-based materials for sustainable control of cyanobacterial blooms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Time-resolved monitoring of microalgae agglomeration facilitates screening of coagulants/flocculants (CFs) from numerous biopolymer candidates. Herein, a filtering-flowing analysis (FFA) apparatus was developed in which dispersed microalgal cells were separated from coagulates and flocs formed by CFs and pumped into spectrophotometer for real-time quantification. Polysaccharides-based CFs for Microcystis aeruginosa and several other microalgae were tested. Cationic hydroxyethyl cellulose (CHEC), chitosan quaternary ammonium (CQA) and cationic guar gum (CGG) all triggered coagulation obeying a pseudo-second-order model. Maximal coagulation efficiencies were achieved at their respective critical dosages, i.e., 0.086 g/g M.a. CHEC, 0.022 g/g M.a. CQA, and 0.216 g/g M.a. CGG. Although not active independently, bacterial exopolysaccharides (BEPS) aided coagulation of M. aeruginosa and allowed near 100% flocculation efficiency when 0.115 g/g M.a. CQA and 1.44 g/g M.a. xanthan were applied simultaneously. The apparatus is applicable to other microalgae species including Spirulina platensis , S. maxima , Chlorella vulgaris and Isochrysis galbana . Bio-based CFs sorted out using this apparatus could help develop cleaner processes for both remediation of harmful cyanobacterial blooms and microalgae-based biorefineries.

As a result of antibiotic overuse, bacterial antibiotic resistance has become a severe threat to worldwide public health. The development of more effective antimicrobial therapies and alternative antibiotic strategies is urgently required. The role played by bacterial membrane vesicles (BMVs) in antibiotic resistance has become a current focus of research. BMVs are nanoparticles derived from the membrane components of Gram-negative and Gram-positive bacteria and contain diverse components originating from the cell envelope and cytoplasm. Antibiotic stress stimulates the secretion of BMVs. BMVs promote and mediate antibiotic resistance by multiple mechanisms. BMVs have been investigated as conceptually new antibiotics and drug-delivery vehicles. In this article, we outline the research related to BMVs and antibiotic resistance as a reference for the intentional use of BMVs to combat antibiotic resistance.

Herein, cobalt-reduced graphene oxide (rGO) catalyst was synthesized with a practical impregnation-calcination approach for the selective hydrodeoxygenation (HDO) of guaiacol to cyclohexanol. The synthesized Co/rGO was characterized by transmission electron microscopy (TEM), high-angle annular dark-field scanning TEM (HAADF-STEM), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, X-ray diffraction (XRD), and H 2 temperature-programmed reduction (H 2 -TPR) analysis. According to the comprehensive characterization results, the catalyst contains single Co atoms in the graphene matrix and Co oxide nanoparticles (CoO x ) on the graphene surface. The isolated Co atoms embedded in the rGO matrix form stable metal carbides (CoC x ), which constitute catalytically active sites for hydrogenation. The rGO material with proper amounts of N heteroatoms and lattice defects becomes a suitable graphene material for fabricating the catalyst. The Co/rGO catalyst without prereduction treatment leads to the complete conversion of guaiacol with 93.2% selectivity to cyclohexanol under mild conditions. The remarkable HDO capability of the Co/rGO catalyst is attributed to the unique metal-acid synergy between the CoC x sites and the acid sites of the CoO x nanoparticles. The CoC x sites provide H while the acid sites of CoO x nanoparticles bind the C-O group of reactants to the surface, allowing easier C-O scission. The reaction pathways were characterized based on the observed reaction-product distributions. The effects of the process parameters on catalyst preparation and the HDO reaction, as well as the reusability of the catalyst, were systematically investigated.

Background: Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disease affecting the motor neurons. Although much research has been conducted in this field, few bibliometric studies have been conducted. This study aimed to provide an overview of publishing characteristics and trends in ALS research since 2000 using a bibliometric analysis., Methods: We conducted a comprehensive literature search in the Web of Science (WOS) Core Collection database for scientific output related to ALS from 2000 to 2022. The retrieved dataset was refined using Google OpenRefine and analyzed using bibliometrix., Results: A total of 29,391 articles published since 2000 were retrieved, with an average annual growth rate of 6.35%. Ninety-six countries and regions contributed to ALS research, among which the United States had the dominant position with the highest number of publications ( n = 8,202) and citations ( n = 558,561). An association analysis was performed to form networks of country collaboration and keyword co-occurrence. The evolution of topic trends was demonstrated in terms of both frequency and proportion., Conclusion: The output of ALS research has increased steadily over the years, and the United States and Western Europe are leaders in this field. There is an upgradation in the pathomechanism and clinical research on ALS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shi, Zhou, Huang and Bi.)

Objective: p75 neurotrophin receptor (p75 NTR ) is associated with the pathogenesis of amyotrophic lateral sclerosis (ALS). However, its role is not fully understood. The aim of this study was to evaluate the association between ALS and the extracellular domain of p75 NTR (p75 ECD ) in urine. Methods: We conducted a comprehensive literature search using keywords in the PubMed, Embase, Science, and the Cochrane Library, and identified five case control studies, with the latest date of search being 18 April 2021. Results: The results showed that urinary p75 ECD levels were significantly higher in patients with ALS compared to non-neurological control (weighted mean difference (WMD) = 4.18, 95% CI [2.525, 6.990], p  < 0.001), and other neurological diseases (WMD = 6.005, 95% CI [1.596, 10.414], p  = 0.008). Increased urinary p75 ECD levels were inversely associated with ALSFRS-R in ALS patients ( r = -0.32, 95% CI [-0.43, -0.21], p  < 0.001). Conclusions: Given the associations between p75 ECD and ALS found in this meta-analysis, urinary p75 ECD levels have potential to be used as a diagnostic biomarker and a progression indicator in the future.

The aim of this study was to investigate the effect of vestibular disruption on autophagy-related proteins and the tumour-associated pathway P13K/Akt in rat sleep and its hypothalamus tissue and to examine whether catechins trigger tumour autophagy. Healthy adult male rats were randomly selected and divided into the vestibular damage group, the sham operation group, and the control group, with 8 rats in each group. A vestibular damage model was established through penetrating the tympanic membrane of the external auditory canal by injecting sodium p-aminophenylarsonate. The electroencephalogram (EGG) activity was used to record the sleep-wakefulness cycle of rats, and the expression levels of hypothalamic orexin (orexin) mRNA and autophagy proteins were detected. Primary hippocampal neurons were intervened with orexin at different concentrations and at different times to detect cell viability and the expression of autophagy protein and P13K/Akt signal pathway protein. The results showed that compared with the control group and the sham operation group, NREM duration in the vestibular damage group decreased significantly ( P < 0.05), while its  W  time increased significantly ( P < 0.05). The expression level of orexin mRNA in the hypothalamus of the vestibular damage group was significantly higher than that of the other two groups ( P < 0.05), the expression of autophagy microtubule-related proteins LC3B and Beclin-1 increased significantly ( P < 0.05), and the protein expression level of p62 decreased significantly ( P < 0.05). After orexin intervention, compared with the control group, the expression of Beclin-1 protein that positively correlated with autophagy decreased significantly ( P < 0.05) and the expression of mTOR, PDK1, and Akt protein increased significantly ( P < 0.05). Compared with the orexin intervention group, the expression of Beclin-1 and LC3B proteins in cells of the orexin receptor inhibitor (Almorexant) group, the autophagy activator (Rapamycin) group, the orexin + Almorexant group, and the orexin + Rapamycin group increased significantly ( P < 0.05), and the expression of mTOR, PDK1, and Akt proteins decreased significantly ( P < 0.05). Catechins trigger autophagy in part by regulating the p-Akt/p-mTOR and P13K pathways and by stimulating the MAPK pathway. Catechins initiate apoptosis in common tumour types of hepatocellular carcinoma cells by activating autophagy-related pathways. The conclusion is that vestibular damage can affect the sleep-wakefulness cycle of rats; the level of autophagy in hypothalamic tissue is upregulated and may affect cell proliferation and activity through mTOR-P13K/Akt, which has a certain reference value for tumor formation and provides a basis for the research of insomnia or sleep disorders caused by tumors. Autophagy activation is a key process by which catechins promote apoptosis in tumour cells, providing an avenue for more research on the use of catechins-rich diets for cardiovascular protection in the treatment of tumours., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Gangli Yan et al.)

Objective: To describe the clinical and neuroimaging features, treatment response and outcomes of adult myelin oligodendrocyte glycoprotein (MOG) antibody-associated cortical encephalitis., Methods: In this retrospective study, adult patients fulling the criteria of encephalitis but not fulfilling those of ADEM and tested positive for serum MOG antibody were recruited from Xiangya Hospital, Central South University (2019-2021). Clinical symptoms, laboratory data, imaging, and outcomes were analyzed., Results: Eleven MOG antibody-associated cortical encephalitis patients consisting of 4 female (36.4%) and 7 male (63.6%) were included with a median onset age of 27 years (ranging: 16-32 years). Fever (8/11), headache (9/11) and seizures (7/11) were the most common symptoms of adult MOG cortical encephalitis, and generalized seizure was the dominant seizure type (4/7). Increased intracranial pressure (5/10, median 280 mm H2O, ranging 240-380 mm H2O), CSF pleocytosis (5/10, median 48 cells/μL, ranging: 18-1800 cells/μL), and protein elevation (4/10, median 0.67 g/L, ranging: 0.46-1.92 g/L) were common. Serum MOG antibody was detected in all patients and the coexistence of CSF NMDAR antibody was found in one case. Imaging showed abnormal brain MRI in 10 patients (90.9%) and 10/10 had the cortical involvement. 8/10 had unilateral lesions while 2/10 had bilateral lesions. 2/10 had the juxta cortical white matter lesions and 2/10 had the corpus callosum lesions. No involvement of deep gray matter or other white matter structure was noted. 5/11 had leptomeningeal and/or lesional enhancements. 10/11 patients had favorable outcomes and 2/11 had clinical relapses with persisting MOG antibody positive during the median follow-up interval of 10 months (ranging: 3-23months)., Conclusion: Atypical clinical features for demyelinating diseases including seizures, remarkably increased intracranial pressure, pleocytosis, and protein elevation are common in MOG cortical encephalitis. Involvement of the corpus callosum and cortex around the midline could be unique imaging features of MOG antibody-associated bilateral cortical encephalitis., (Copyright © 2022. Published by Elsevier B.V.)

Blood circulating microRNAs (miRNAs) are proposed to be promising biomarkers for many neurodegenerative disorders, including Parkinson's disease (PD). However, there is a lack of identified differentially expressed miRNAs in PD from different studies. The aim of this study was to evaluate miRNAs expression in PD. We measured plasma circulating miRNA expression in three independent sets with a total of 151 PD patients, 21 multiple system atrophy (MSA) patients and 138 healthy controls using high-throughput RT-PCR. We identified that elevated miR-133b and miR-221-3p discriminated early-stage PD from controls with 94.4% sensitivity and 91.1% specificity. Elevated miR-133b and miR-221-3p distinguished PD from controls with 84.8% sensitivity and 88.9% specificity. In addition, miR-4454 distinguished PD from MSA with 57.1% sensitivity and 82.6% specificity. Hence, elevated miR-133b and miR-221-3p potentially represent good biomarkers for early PD, and a combination of miR-133b, miR-221-3p and miR-4454 has the potential to serve as a non-invasive biomarker for PD diagnosis., (© 2021. The Author(s).)

Objectives: The epidemiological and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) have been researched. However, the prevalence of repositivity by real-time PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. Methods: A retrospective study was conducted involving 599 discharged patients with COVID-19 in a single medical centre. The clinical features of patients during their hospitalization and 14-day post-discharge quarantine were collected. Results: A total of 122 patients (20.4%) out of 599 patients retested positive after discharge. Specifically, 94 (15.7%) retested positive within 24 h of discharge, and another 28 patients (4.7%) were repositive on day 7 after discharge, although none showed any clinical symptomatic recurrence. Both repositives and non‑repositives have similar patterns of IgG and IgM. Notably, the length of hospitalization of non-repositive patients was longer than that of 24-h repositive patients and 7-day repositive patients. In addition, the length of hospitalization of 24-h repositive patients was shorter than that of 7-day repositive patients, indicating that the length of hospitalization was also a determinant of viral shedding. Conclusion: Our study provides further information for improving the management of recovered and discharged patients, and further studies should be performed to elucidate the infectiveness of individuals with prolonged or RNA repositivity., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The prevalence of sleep disorders and cognitive dysfunction has overwhelmingly increased, with insomnia and Alzheimer's disease (AD) being the most common form. A multitude of studies have linked the alterations in sleep continuity or sleep architecture with cognitive impairment bilaterally, but the management of disrupted sleep patterns in preclinical AD could be more beneficial since there is no cure for AD. This review mainly focuses on the altered sleep patterns in insomnia, and summarizes potential pathways underlying the relationship between insomnia and cognitive impairment, aiming to establish certain sleep pattern changes as biomarkers for cognitive decline and explore potential therapeutic targets based on evidence from research advances., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Pioglitazone may have potential benefits in the treatment of cutaneous and metabolic derangements of psoriasis, but its role in the treatment of psoriasis remains in debate. We therefore conducted a meta-analysis to evaluate the clinical efficacy and safety of pioglitazone in psoriasis vulgaris (PsV).We performed a comprehensive search in database of PubMed, Web of Science, Cochrane library, Embase and China National Knowledge Infrastructure (CNKI), and Wan fang database through March 2019 to identify eligible studies. Randomized controlled trials that have evaluated the effect and safety of pioglitazone in PsV were included. Treatment success was defined as ≥75% reduction in psoriasis area and severity index (PASI) score after treatment. Weighted mean differences (WMD), relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were pooled to compare the clinical efficacy and safety between different groups.Six randomized controlled trials (n = 270) were included. Meta-analysis showed that pioglitazone was associated with a remarkable reduction in PASI score in patients with PsV (weight mean difference: 2.68, 95% CI 1.41-3.94, P < .001). The treatment success rate in the pioglitazone group was higher than in the control group (RR 3.60, 95 CI 1.61-8.01, P < .001). Compared with control group, pioglitazone was not related to a pronounced increase in total adverse events (RR 1.180, 95 CI 0.85-1.63, P = .33). Moreover, the risk of common adverse events in the 2 groups were similar, such as elevated liver enzyme, fatigue, nausea, weight gain.This meta-analysis suggested pioglitazone is an effective and safe drug in the treatment of patients with PsV.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease accompanied with severe paralysis or even death, while the pathogenesis of ALS is still unclear and no effective therapy exists. The accumulating evidence has indicated the association between gut microbiota and various neurological diseases. Thus, to explore the potential role of gut microbiome in ALS, 20 patients diagnosed with probable or definite ALS and 20 healthy controls were enrolled and their fecal excrements were collected. The analysis of fecal community diversity with 16S rDNA sequencing showed an obvious change in microbial structure of ALS patients, where Bacteroidetes at the phylum level and several microbes at the genus level were up-regulated, while Firmicutes at the phylum level and Megamonas at the genus level were down-regulated compared to healthy controls. Additionally, decreased gene function associated with metabolic pathways was observed in ALS patients. The metagenomics further demonstrated the discrepancies in microflora at the species level and relevant metabolites thereof were also revealed when combined with metabolomics. In conclusion, the altered composition of the gut microbiota and metabolic products in ALS patients provided deeper insights into the pathogenesis of ALS, and these biomarkers might be established as potential therapeutic targets which deserve further exploration.

EPM2A has been certified as a causative gene in patients with Lafora disease (LD), which is a rare autosomal recessive and severe form of progressive myoclonus epilepsy. LD classically starts in adolescence, characterized by various types of seizure with myoclonic seizure as the main type. Typically within 10 years, intractable seizure attack, rapidly progressing dementia, and a vegetative state were present. LD is particularly frequently found in Mediterranean countries. Here, we report a Chinese family with a novel compound heterozygous mutation in the EPM2A gene, characterized by recurrent vomiting, intractable epilepsy, and progressive cognitive decline.

Novel molecular signatures are needed to improve the early and accurate diagnosis of autism spectrum disorder (ASD), and indicate physicians to provide timely intervention. This study aimed to identify a robust blood non-coding RNA (ncRNA) signature in diagnosing ASD. One hundred eighty six blood samples in the microarray dataset were randomly divided into the training set (n = 112) and validation set (n = 72). Then, the microarray probe expression profile was re-annotated into the expression profile of 4143 ncRNAs though probe sequence mapping. In the training set, least absolute shrinkage and selection operator (LASSO) penalized generalized linear model was adopted to identify the 20-ncRNA signature, and a diagnostic score was calculated for each sample according to the ncRNA expression levels and the model coefficients. The score demonstrated an excellent diagnostic ability for ASD in the training set (area under receiver operating characteristic curve [AUC] = 0.96), validation set (AUC = 0.97) and the overall (AUC = 0.96). Moreover, the blood samples of 23 ASD patients and 23 age- and gender-matched controls were collected as the external validation set, in which the signature also showed a good diagnostic ability for ASD (AUC = 0.96). In subgroup analysis, the signature was also robust when considering the potential confounders of sex, age, and disease subtypes. In comparison with a 55-gene signature deriving from the same dataset, the ncRNA signature showed an obviously better diagnostic ability (AUC: 0.96 vs 0.68, P < .001). In conclusion, this study identified a robust blood ncRNA signature in diagnosing ASD, which might help improve the diagnostic accuracy for ASD in clinical practice.

Background: Amyotrophic lateral sclerosis (ALS) is a neurological disorder clinically characterized by motor system dysfunction, with intraneuronal accumulation of the TAR DNAbinding protein 43 (TDP-43) being a pathological hallmark. Riluzole is a primarily prescribed medicine for ALS patients, while its therapeutical efficacy appears limited. TDP-43 transgenic mice are existing animal models for mechanistic/translational research into ALS., Methods: We developed a transgenic rat model of ALS expressing a mutant human TDP-43 transgene (TDP-43M337V) and evaluated the therapeutic effect of Riluzole on this model. Relative to control, rats with TDP-43M337V expression promoted by the neurofilament heavy subunit (NEF) gene or specifically in motor neurons promoted by the choline acetyltransferase (ChAT) gene showed progressive worsening of mobility and grip strength, along with loss of motor neurons, microglial activation, and intraneuronal accumulation of TDP-43 and ubiquitin aggregations in the spinal cord., Results: Compared to vehicle control, intragastric administration of Riluzole (30 mg/kg/d) did not mitigate the behavioral deficits nor alter the neuropathologies in the transgenics., Conclusion: These findings indicate that transgenic rats recapitulate the basic neurological and neuropathological characteristics of human ALS, while Riluzole treatment can not halt the development of the behavioral and histopathological phenotypes in this new transgenic rodent model of ALS., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Reliable molecular signatures are needed to improve the early and accurate diagnosis of autism spectrum disorder (ASD), and indicate physicians to provide timely intervention. This study aimed to identify a robust blood small nuclear RNA (snRNA) signature in diagnosing ASD. 186 blood samples in the microarray dataset were randomly divided into the training set (n = 112) and validation set (n = 72). Then, the microarray probe expression profiles were re-annotated into the expression profiles of 1253 snRNAs though probe sequence mapping. In the training set, least absolute shrinkage and selection operator (LASSO) penalized generalized linear model was adopted to identify the 9-snRNA signature (RNU1-16P, RNU6-1031P, RNU6-258P, RNU6-335P, RNU6-485P, RNU6-549P, RNU6-98P, RNU6ATAC26P, and RNVU1-15), and a diagnostic score was calculated for each sample according to the snRNA expression levels and the model coefficients. The score demonstrated a good diagnostic ability for ASD in the training set (area under receiver operating characteristic curve (AUC) = 0.90), validation set (AUC = 0.87), and the overall (AUC = 0.88). Moreover, the blood samples of 23 ASD patients and 23 age- and gender-matched controls were collected as the external validation set, in which the signature also showed a good diagnostic ability for ASD (AUC = 0.88). In subgroup analysis, the signature was robust when considering the confounders of gender, age, and disease subtypes, and displayed a significantly better performance among the female and younger cases (P = .039; P = .002). In comparison with a 55-gene signature deriving from the same dataset, the snRNA signature showed a better diagnostic ability (AUC: 0.88 vs 0.80, P = .049). In conclusion, this study identified a novel and robust blood snRNA signature in diagnosing ASD, which might help improve the diagnostic accuracy for ASD in clinical practice. Nevertheless, a large-scale prospective study was needed to validate our results.

Background: Mutant transactive response DNA-binding protein (TDP-43) is closely correlated to the inherited form of amyotrophic lateral sclerosis (ALS). TDP-43 transgenic rats can reproduce the core phenotype of ALS and constitutive expression of TDP-43 caused postnatal death., Objective: The study aimed to understand whether neurologic deficiency caused by mutant TDP- 43 is dependent on its temporal expression., Method: Transgenic rats were established that express mutant human TDP-43 (M337V substitution) in neurons, then a Tet-off system was used to regulate its expression., Results: TDP-43 mutant transgenic rats developed significant weakness after the transgene was activated. Rats with expression of mutant TDP-43 at 30 days showed a more aggressive phenotype. More severe pathological changes in neurogenic atrophy were observed in these rats., Conclusion: Temporal expression of mutant TDP-43 in neurons promoted serious phenotype in rats. The dysfunction of TDP-43 had a profound impact on the development of motor neurons and skeletal muscles., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive cognitive decline. It can be divided into familial AD (FAD) and sporadic AD (SAD) based on the family history. Recently dysregulation of cholesterol homeostasis has been implicated in the development of late-onset AD. ATP-binding cassette transporter A7 (ABCA7) gene, regulating the transport of cholesterol, has been recently identified as a susceptible gene of AD by several large genome-wide association studies. To test the genetic effect of ABCA7 rs3764650 on blood lipid levels in Southern Chinese Han population and investigate the risk factors of SAD, a total of 118 SAD patients and 120 healthy matched controls were recruited and the genotyping in ABCA7 rs3764650 was conducted on the Sequenom MassARRAY iPLEX platform. Meanwhile, the levels of fasting lipid profile and mini-mental state examination (MMSE) scores were tested. There was significant difference in genotype distribution between SAD patients and controls (p=0.001). While the difference of ABCA7 rs3764650 allele distribution between SAD patients and controls was only significant in APOEε4-noncarriers (p=0.039). The association between blood lipid levels and ABCA7 rs3764650 genotypes was influenced by APOEε4 status. In APOEε4-noncarriers of SAD, the total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels in GG genotype group were significantly lower than those in GT and TT genotype groups (all p<0.05). Whereas no significant difference of blood lipid levels was found among three genotypes in APOEε4-carriers of SAD and controls. Additionally, logistic regression analysis showed that lower high-density lipoprotein cholesterol (HDL-C) levels (p=0.015, OR=5.669) and GG genotype (p=0.013, OR=8.318) were positively associated with SAD. Our results suggest that GG genotype of ABCA7 rs3764650 was a risk factor of SAD in Southern Chinese Han population as well as lipid homeostasis., (Copyright © 2017. Published by Elsevier B.V.)

Paroxysmal kinesigenic dyskinesia (PKD) is characterized by recurrent and brief attacks of dystonia or chorea precipitated by sudden movements. It can be sporadic or familial. Proline-Rich Transmembrane Protein 2 (PRRT2) has been shown to be a common causative gene of PKD. However, less than 50% of patients with primary PKD harbor mutations in PRRT2. The aim of this study is to use eight families with PKD to identify the pathogenic PRRT2 mutations, or possible novel genetic cause of PKD phenotypes. After extensive clinical investigation, direct sequencing and mutation analysis of PRRT2 were performed on patients from eight PKD families. A genome-wide STR and SNP based linkage analysis was performed in one large family that is negative for pathogenic PRRT2 mutations. Using additional polymorphic markers, we identified a novel gene locus on chromosome 3q in this PRRT2-mutation-negative PKD family. The LOD score for the region between markers D3S1314 and D3S1256 is 3.02 and we proposed to designate this locus as Episodic Kinesigenic Dyskinesia (EKD3). Further studies are needed to identify the causative gene within this locus.

Background: Although predominantly reported in patients with status epilepticus, periictal MRI abnormalities have been reported in patients with a single or a cluster of seizures. Clinicians are often presented with a dilemma concerning the features of MRI abnormalities induced by a single or a cluster of seizures, as they may represent the effect of seizure activity rather than its structural cause., Methods: A retrospective review of clinical and neuroimaging charts of 14 patients diagnosed with a single or a cluster of seizure-related MR-signal changes from the database of our unit (approximately 300 patients diagnosed with a single or a cluster of seizures underwent brain-MRI within 14 days from a seizure) was conducted. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined., Results: MRI showed unilateral abnormalities in 14 patients, with hyperintensities on T2-signal (12/14), fluid-attenuated inversion-recovery (FLAIR) (12/14), and restricted diffusion (6/8). Location of abnormality was cortical (4/14), subcortical (6/14), thalamus (2/14), corpus callosum (1/14), and bordering an old encephaloclastic lesion (1/14). Periictal MRI abnormalities and electroclinical findings in 10 patients showed an almost complete topographic concordance, which was not consistent in 4 patients. Reversibility of MRI changes was complete in 11 patients, partially disappeared in 1 patient, and irreversible on MRI in 2 patients., Conclusions: A single or a cluster of seizures cannot only induce transient, variably reversible MRI brain abnormalities, but also irreversible changes. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Substantial evidence implicates abnormal protein kinase function in various aspects of Parkinson's disease (PD) etiology. Elevated phosphorylation of the PD-defining pathological protein, α-synuclein, correlates with its aggregation and toxic accumulation in neurons, whilst genetic missense mutations in the kinases PTEN-induced putative kinase 1 and leucine-rich repeat kinase 2, increase susceptibility to PD. Experimental evidence also links kinases of the phosphoinositide 3-kinase and mitogen-activated protein kinase signaling pathways, amongst others, to PD. Understanding how the levels or activities of these enzymes or their substrates change in brain tissue in relation to pathological states can provide insight into disease pathogenesis. Moreover, understanding when and where kinase dysfunction occurs is important as modulation of some of these signaling pathways can potentially lead to PD therapeutics. This review will summarize what is currently known in regard to the expression of these PD-implicated kinases in pathological human postmortem brain tissue.

Objectives: To investigate the effects of local mild hypothermia on the expression of Fas, FasL and MMP-3 after cerebral ischemia-reperfusion in rats., Materials and Methods: Male Wistar rats were divided into sham-operated group (Sham), normothermia group (NT), and hypothermia group (HT). MCAO/R model was established by Longa's method, and reperfusion was allowed after 2 hr occlusion. Mild hypothermia (33±0.5°C) for 6 hr was initiated at the start of reperfusion. Immunohistochemistry was performed to determine expression Fas, FasL, and MMP-3., Results: Infarct volume was reduced in the hypothermia group (18.43±4.23%) compared with the normothermia group (24.76±5.76%) (P<0.05). In mild hypothermia group, numbers of Fas-positive and MMP-3 positive cells were significantly less than those of normothermia group (P<0.05). Neurological functional scores of mild hypothermia were significantly improved (P<0.05)., Conclusion: Mild hypothermia decreases infarct volume after cerebral ischemia-reperfusion, reduces Fas and MMP-3 expression, but increases FasL in cerebral ischemia-reperfusion rats.

Depression has been associated with reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. Genetic association studies of the BDNF Val66Met polymorphism (rs6265) in geriatric depression have produced inconsistent results. A meta-analysis of studies was conducted to compare the frequency of the BDNF Val66Met variant between cases with geriatric depression and age-matched controls. A total of five studies involving 523 cases with geriatric depression and 1,220 psychiatrically healthy controls was included. Met allele carriers had an increased risk for geriatric depression when compared to Val/Val homozygotes (P = 0.004, OR = 1.48, 95% CI = 1.13-1.93). Our findings suggest the BDNF Met allele may confer increased risk for depression as individual age., (Copyright © 2012 Wiley Periodicals, Inc.)

Lewy bodies are made from insoluble, phosphorylated α-synuclein, but the earliest changes that precipitate such pathology still remain conjecture. In this study, we quantify and identify relationships between the levels of the main pathologic form of phosphorylated α-synuclein over the course of Parkinson's disease in regions affected early through to end-stage disease. Brain tissue samples from 33 cases at different disease stages and 13 controls were collected through the Australian Network of Brain Banks. 500 mg of frozen putamen (affected preclinically) and frontal cortex (affected late) was homogenized, fractionated and α-synuclein levels evaluated using specific antibodies (syn-1, BD Transduction Laboratories; S129P phospho-α-synuclein, Elan Pharmaceuticals) and quantitative western blotting. Statistical analyses assessed the relationship between the different forms of α-synuclein, compared levels between groups, and determined any changes over the disease course. Soluble S129P was detected in controls with higher levels in putamen compared with frontal cortex. In contrast, insoluble α-synuclein occurred in Parkinson's disease with a significant increase in soluble and lipid-associated S129P, and a decrease in soluble frontal α-synuclein over the disease course. Increasing soluble S129P in the putamen correlated with increasing S129P in other fractions and regions. These data show that soluble non-phosphorylated α-synuclein decreases over the course of Parkinson's disease, becoming increasingly phosphorylated and insoluble. The finding that S129P α-synuclein normally occurs in vulnerable brain regions, and in Parkinson's disease has the strongest relationships to the pathogenic forms of α-synuclein in other brain regions, suggests a propagating role for putamenal phospho-α-synuclein in disease pathogenesis.

Background: Schistosoma japonicum is the most widespread schistosoma in the world. Although gastrointestinal system involvement with S japonicum appears to be considerably common, cerebral schistosomiasis is not frequent. Cerebral schistosomiasis japonica intestinal and hepatosplenic involvement is more rare. We collected 2 cases of cerebral schistosomiasis identified by pathological diagnosis, lacking extracranial involvement. In addition, one of them had multiple lesions, which was also rare., Case Description: Two male patients came from Dongting Lake region, Hunan province, one of the oldest and most severe endemic areas of China. Their clinical symptoms varied, such as headache, dizziness, seizures, and others. Studies in blood were normal except for eosinophilia. Computed tomography of brains showed hyperdense areas, and MRI showed isointense signal on T1-weighted images, hyperintense signal on T2-weighted images, and heterogeneous enhancement. The definitive diagnosis was cerebral schistosomiasis japonium by biopsy. Standard use of praziquantel and corticosteroid drugs was applied, and the prognosis was good., Conclusion: Cerebral schistosomiasis japonica without intestinal and hepatosplenic involvement is exactly rare and easily ignored. The diagnosis sometimes is difficult. Laboratory and imaging examinations are helpful but not specific. Although operation can give the definitive diagnosis, it is not imperative. The administration of praziquantel and corticosteroid drugs in early stages is good for prognosis.

Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurologic inherited disease with heterogeneity. Autosomal dominant (AD) is the common inherited mode. There have been two loci mapped to 16 chromosome for PKD. However, no gene responsible for it has been identified so far. We collected 6 pedigrees from Chinese mainland. There were 122 members in all, including 26 affected. According to New diagnostic criteria of Bruno, they were diagnosed as pure PKD. From the clinic data, we found that the onset age was earlier and the severity was increasing in the subsequent generations in 4 pedigrees of them, which suggested genetic anticipation. Linkage analysis was applied in 2 of these pedigrees. The maximum LOD score and NPL score were negative. The followed haplotypes analysis excluded the PKD locus in both families from chromosome 16, providing evidence for a novel locus.