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Background: Familial encephalopathy with neuroserpin inclusion bodies (FENIB), a rare neurogenetic disease, is characterized by progressive cognitive decline and myoclonus and caused by pathogenic variants of the SERPINI1 gene that lead to the formation of neuroserpin inclusion bodies.Methods: We described the case of an Asian patient with FENIB associated with a pathogenic variant of SERPINI1 and summarized and analyzed the clinical characteristics of the case. In addition, we conducted a literature review of previously reported patients with this disease.Results: The patient, a 16-year-old Chinese girl, presented with progressive cognitive decline and myoclonus that had started at the age of 11 years. The girl was found to carry a de novo heterozygous c.1175G>A (p.G392E) variant of the SERPINI1 gene, which is a pathogenic variant according to the guidelines of the American College of Medical Genetics and Genomics. She had responded poorly to antiseizure medications (ASMs). At the last follow-up, her myoclonus was still out of control, and her self-care ability was poor. Our literature review revealed that 13 similar cases (including 9 cases in male patients) have been reported so far, in which six pathogenetic variations in SERPINI1, including G392E, were responsible for FENIB. All the patients presented with myoclonus, and 12 patients had experienced at least one other type of seizure. Further, as observed in our case, 9 out of 12 patients did not respond to ASMs. Progressive cognitive decline was observed in all the patients, and 10 out of 13 patients had dyskinesia. The median age of disease onset was 21 years, and the median age at the time of death was 33 years. Further, 9 out of 13 patients showed signs of cerebral and/or cerebellar atrophy. Finally, neuroserpin inclusion bodies were identified in six patients who underwent brain biopsy or autopsy.Conclusions: Pathogenic variants of SERPINI1 should be suspected in children with progressive cognitive decline and myoclonus, especially in those with progressive myoclonus epilepsy. Further, gene detection and brain biopsy are important means for the diagnosis of FENIB. [ABSTRACT FROM AUTHOR]

Purpose: Most SCN1A missense variants located outside the sodium channel core region show a mild phenotype. However, there are exceptions, because of which it is challenging to determine the correlation between genotype and phenotype. In this study, we aimed to determine whether functional study could be used to determine disease severity in cases with such variants, and elucidate possible genotype-phenotype relationships.Methods: Forty-seven patients with SCN1A missense variants were recruited, and one with a Dravet syndrome phenotype with an SCN1A missense variant (c.3811T>C/ p.W1271R) located outside the core region was screened with electrophysiological tests. We also reviewed functional SCN1A studies on patients with inconsistent phenotypes and genotypes, and studied the relationship between electrophysiological measurements and clinical phenotype.Results: Patch clamp experiments showed that the W1271R variant caused significantly reduced sodium current, decreased channel voltage sensitivity, loss of channel availability, and prolonged recovery time from inactivation compared with wild type (WT), which ultimately caused a change in loss of function (LOF). Twelve cases of severe SCN1A-related epilepsy with missense variants located outside the channel core region were also included from the functional studies. Nine patients with missense SCN1A variants showed complete (3/9) or partial (6/9) physiological LOF. Two missense SCN1A variants caused physiological gain-and-loss of function (G-LOF), and one caused decreased excitability (DE).Conclusions: Not all missense variants located outside the core region cause a mild phenotype. Although current functional studies in heterologous expression systems do not accurately reflect disease severity caused by SCN1A missense variants, they could be an effective model for generation of data to study the initial effects of SCN1A missense variants. [ABSTRACT FROM AUTHOR]

Background: Viral encephalitis is an important trigger for anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. We analyzed the clinical characteristics of anti-NMDAR encephalitis after Japanese encephalitis (JE) in children.Methods: Clinical data of 185 children with anti-NMDAR encephalitis were retrospectively reviewed. Patients with a history of viral encephalitis other than JE or who were identified with other autoantibodies were excluded.Results: Twenty children with anti-NMDAR encephalitis after JE were enrolled with a median age of 6 years and 10 months (interquartile range [IQR]: 3 years to 11 years and 5 months). The median time from JE to anti-NMDAR encephalitis was 29 (IQR: 25 to 32) days. At 12 months, most patients (17 of 18) recovered to at least their baseline modified Rankin scale (mRS) scores caused by JE. One hundred forty two children with classical anti-NMDAR encephalitis were enrolled. Compared with classical anti-NMDAR encephalitis, patients after JE had significantly more decreased level of consciousness (50% vs 18.3%, P = 0.003), more autonomic dysfunction (30.0% vs 9.9%, P = 0.021), fewer psychiatric or behavioral symptoms (70.0% vs 90.8%, P = 0.016), fewer seizures (25.0% vs 68.3%, P < 0.001), lesser improvement 4 weeks after immunotherapy (35.0% vs 73.2%, P = 0.001), and worse outcomes at 12 months (median mRS: 1 vs 0, P < 0.001).Conclusions: Anti-NMDAR encephalitis after JE in children mainly occurred within two months. Their clinical manifestation may differ from classical anti-NMDAR encephalitis. The prognosis of children with anti-NMDAR encephalitis after JE probably depends on the neurological sequelae after JE. [ABSTRACT FROM AUTHOR]

Super-enhancers are large domains on the genome where multiple short typical enhancers within a specific genomic distance are stitched together. Typically, they are cell type-specific and responsible for defining cell identity and regulating gene transcription. Numerous studies have demonstrated that super-enhancers are enriched for trait-associated variants, and mutations in super-enhancers are possibly related to known diseases. Recently, several machine learning-based methods have been used to distinguish super-enhancers from typical enhancers by using high-throughput data from various experimental methods. The acquisition of such experimental data is usually costly and time-consuming. In this paper, we innovatively proposed SENet, a groundbreaking method based on a deep neural network model, for discriminating between the two categories solely utilizing sequence information. SENet employs dna2vec feature embedding, convolution for local feature extraction, attention pooling for refined feature retention, and Transformer for contextual information extraction. Experiments demonstrate that SENet outperforms all current state-of-the-art computational methods and shows satisfactory performance in cross-species validation. Our method pioneers the distinction between super-enhancers and typical ones using only sequence information. The source code and datasets are stored in https://github.com/lhy0322/SENet. [Display omitted] • The first benchmark dataset discriminating between super enhancers and typical enhancers was compiled. • A novel deep learning architecture named SENet is proposed to discriminate human and mouse super- and typical enhancers. • Comparative studies have shown that SENet outperforms existing models in discriminating super-enhancers. • SENet performs well in cross-species prediction, which facilitates the discrimination of other species. [ABSTRACT FROM AUTHOR]

Epidemiological studies have established a robust correlation between exposure to ambient particulate matter (PM) and various neurological disorders, with dysregulation of intracellular redox processes and cell death being key mechanisms involved. Ferroptosis, a cell death form characterized by iron-dependent lipid peroxidation and disruption of antioxidant defenses, may be involved in the neurotoxic effects of PM exposure. However, the relationship between PM-induced neurotoxicity and ferroptosis in nerve cells remains to be elucidated. In this study, we utilized a rat model (exposed to PM at a dose of 10 mg/kg body weight per day for 4 weeks) and an HT-22 cell model (exposed to PM at concentrations of 50, 100, and 200 μg/mL for 24 h) to investigate the potential induction of ferroptosis by PM exposure. Furthermore, RNA sequencing analysis was employed to identify hub genes that potentially contribute to the process of ferroptosis, which was subsequently validated through in vivo and in vitro experiments. The results revealed that PM exposure increased MDA content and Fe2+ levels, and decreased SOD activity and GSH/GSSG ratio in rat hippocampal and HT-22 cells. Through RNA sequencing analysis, bioinformatics analysis, and RT-qPCR experiments, we identified GSK3B as a possible hub gene involved in ferroptosis. Subsequent investigations demonstrated that PM exposure increased GSK3B levels and decreased Nrf2, and GPX4 levels in vivo and in vitro. Furthermore, treatment with LY2090314, a specific inhibitor of GSK3B, was found to mitigate the PM-induced elevation of MDA and ROS and restore SOD activity and GSH/GSSG ratio. The LY2090314 treatment promoted the upregulation of Nrf2 and GPX4 and facilitated the nuclear translocation of Nrf2 in HT-22 cells. Moreover, treatment with LY2090314 resulted in the upregulation of Nrf2 and GPX4, along with the facilitation of nuclear translocation of Nrf2. This study suggested that PM-induced ferroptosis in hippocampal cells may be via the GSK3B/Nrf2/GPX4 pathway. [Display omitted] • PM exposure induces ferroptosis in hippocampal cells. • GSK3B may serve as a hub gene in ferroptosis induced by PM. • The GSK3B/Nrf2/GPX4 pathway may exert a pivotal role in ferroptosis induced by PM. [ABSTRACT FROM AUTHOR]

Chemical doping is an indispensable tool to tailor the properties of the commercial piezoelectric materials. However, a high piezoelectric coefficient with enhanced thermal stability is rarely achieved by one dopant in some high-performance ferroelectrics, e.g., the recently discovered eco-friendly (Ba 0.85 Ca 0.15)(Zr 0.1 Ti 0.9)O 3 (BCZT) ceramics. In order to optimize the piezoelectric property in BCZT system by a simple way, we investigated the doping effect of Fe3+, Nb5+ and Bi3+ cations in BCZT ceramics respectively. The results indicate that only Nb5+-doped BCZT ceramics display a combination of large piezoelectric coefficient and enhanced thermal stability, compared with others. Moreover, the established phase diagrams and in-situ transmission electron microscope (TEM) observations reveal that such optimized piezoelectric properties after Nb5+ doping originates from (i) the low polarization anisotropy near the ambient tetragonal (T)-orthorhombic (O) phase transition and (ii) the easy domain wall motion of persistent miniaturized ferroelectric domains upon heating. [ABSTRACT FROM AUTHOR]

Few studies have investigated the associations between heavy metals and anxiety. The purpose of this study was to examine the associations between single and combined exposure to heavy metals and anxiety. This study employed data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Anxiety was assessed by patients self-reporting the number of anxious days per month. First, we evaluated the associations between 10 heavy metals single exposure and anxiety by multivariable logistic regression. We then selected 5 heavy metals (cadmium, antimony, cobalt, tungsten, and uranium) for further analysis by elastic net regression. Subsequently, principal component analysis (PCA), weighted quantile regression (WQS), and Bayesian kernel machine regression (BKMR) were utilized to evaluate the associations between 5 heavy metals co-exposure and anxiety. This study included 4512 participants, among whom 1206 participants were in an anxiety state. Urinary cadmium and antimony were separately related to an increased risk of anxiety (p for trend <0.01 and < 0.01, respectively). In PCA analysis, PC1 was associated with an increased risk of anxiety (p for trend <0.001). In WQS analysis, the positive WQS index was substantially linked with the risk of anxiety (OR (95%CI): 1.23 (1.04,1.39)). In BKMR analysis, the overall effects of co-exposure to heavy metals were positively connected with anxiety. Our study identified a positive correlation between individual exposure to cadmium and antimony and the risk of anxiety. Additionally, the co-exposure to cadmium, antimony, cobalt, tungsten, and uranium was associated with an increased risk of anxiety. [Display omitted] This is the first general population study on heavy metals and anxiety. We employed four statistical methods for comprehensive verification. Urinary cadmium and antimony were separately related to an increased risk of anxiety. The co-exposure to heavy metals was associated with an increased risk of anxiety. [ABSTRACT FROM AUTHOR]

Flavonoids may have a protective effect against depression. The purpose of this study was to examine whether flavonoid intake was associated with depression. This is an observational cross-sectional study. We evaluated a sample of 8183 adults from the National Health and Nutrition Examination Survey (NHANES), 2007–2010. The participants had an average age of 46.7 years, and 48.4% of them were male. Flavonoid intake was obtained through dietary recall interviews, and it included six subclasses: isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols. Depression was identified using the Patient Health Questionnaire (PHQ-9). Logistic regression was utilized to evaluate the association between flavonoid intake and depression. Restricted cubic splines (RCS) were utilized to investigate nonlinear associations. Differences between subgroups were explored. Mediation analysis was used to explore confounding/mediating factors. These models were adjusted for age, sex, race/ethnicity, poverty status, education, smoking status, alcohol consumption, BMI, energy intake, physical activity, and chronic diseases. There were 765 individuals with depression (PHQ-9 score ≥ 10) in the sample. After adjusting for covariates, flavanones, flavones, and total flavonoid intake were associated with a lower likelihood of depression (OR (95% CI): 0.73(0.64,0.84); 0.36(0.21,0.63); 0.86(0.74,0.99), respectively). A significant inverse correlation was observed between flavonoid consumption and the somatic symptom score of the PHQ-9. We observed a stronger association between flavonoids and depression in non-Hispanic white groups. The relationship between the total flavonoid intake and depression was explained to some extent by sleep duration (13.8%). Flavonoid intake was associated with lower odds of depression. [Display omitted] • Flavonoid intake of 8183 adults was measured through dietary recall interviews. • Depression was identified using the 9-item Patient Health Questionnaire (PHQ-9). • A flavonoid-rich diet was associated with depression (i.e., PHQ-9 score ≥ 10). • This association was stronger among in non-Hispanic white participants. • This association was partially confounded or mediated by sleep duration. [ABSTRACT FROM AUTHOR]

Abstract Strain glass, a glassy state of lattice strain, has been found in Ti 50- x Ni 50+ x alloys and later in many metallic ferroelastic/martensitic systems, where shear or shuffle serves as a primary order parameter (POP). Another class of non-metallic ferroelastic ceramics are also known to widely exist and commonly possess a polyhedral tilt as the POP. So far, it is unclear whether a "tilt" strain glass exists. Here, we report a finding of a tilt strain glass in La 1- x Sr x Al 0.95 Nb 0.05 O 3-δ ceramics. With increasing Sr2+ dopants, the ferroelastic transition from cubic to rhombohedral phases is gradually suppressed. At a critical concentration (x c ∼10%), a strain glass transition emerges, characterized by five sets of evidence: (I) an invariance of average structure; (II) frequency dependence of elastic moduli at a strain glass transition temperature T g ; (III) non-ergodicity; (IV) formation of rhombohedral nanodomains; (V) a gradual increase of tilt angle upon cooling. Surprisingly, the established phase diagram shows an increase of T g with increasing dopants (a positive correlation), which is different from previous strain glass phase diagrams. The positive and negative correlations can be explained as a balance between two factors of strain glass transition: a global transition factor producing a negative contribution competes with a local field one producing a positive contribution. Our discovery of strain glass in ceramics may also bring novel properties as in metals. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

When a gas passes through the surface of a liquid pool, bubbles are formed at the liquid surface.Thus, the liquid can be directly released into the atmosphere via bubble bursting above the pool surface.This phenomenon is prevalent in several fields, such as chemical industries marine aerosol environments, and nuclear engineering.If a liquid pool contains aerosols, the aforementioned phenomenon will directly become a means of releasing the through fall droplets.This is an important mechanism for releasing liquids and aerosols from pools.Therefore, it is important to study the phenomenon of bubble bursting and to derive the distribution of droplets to evaluate the mechanism of release.With this objective, an experimental visualization platform was designed; the process of bubble bursting was photographed using a high-speed camera,and the images were processed to obtain the distributions of the droplets released.The results shows that hundreds of droplets are formed via bubble bursting at the surface of the liquid, and the distribution of the droplets is different under different conditions of the liquid.In distilled water, the number of droplets formed via bubble bursting is less than in regular water, while the sizes of the droplets increase with an increase in temperature.Furthermore, in a suspension of TiO 2 at a temperature of about 16 °C, the mass concentration is not a key factor inthe release of the droplets.However, at high temperatures of about 50 °C and 77 °C,with an increasing mass concentration ofTiO 2 , the number of droplets formed via bubble bursting increases, while the dropletsizes decrease.This indicates that with an increase in the concentration of aerosols, more droplets and aerosols will be released via bubble bursting. Image 1 • The distribution of quantity and sizes of droplets generated by bubble bursting at liquid surface under condition of distill water and TiO2 aerosols were study. • The entrainment of aerosols by bubble bursting at liquid surface under different conditions were study. [ABSTRACT FROM AUTHOR]