BACKGROUND: The use of both edaravone (EDA) and hyperbaric oxygen therapy (HBOT) is increasingly prevalent in the treatment of delayed encephalopathy after carbon monoxide poisoning (DEACMP). This meta-analysis aims to evaluate the efficacy of using EDA and HBOT in combination with HBOT alone in the treatment of DEACMP.
METHODS: We searched and included all randomized controlled trials (RCTs) published before November 6, 2023, from 12 Chinese and English databases and clinical trial centers in China and the United States. The main outcome indicator was the total effective rate. The secondary outcome indicators included the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), Hasegawa Dementia Scale (HDS), Fugl-Meyer Assessment (FMA), Superoxide Dismutase (SOD), and Malondialdehyde (MDA). Statistical measures utilized include risk ratios (RR), weighted mean difference (WMD), and 95 % confidence intervals (95 % CI).
RESULTS: Thirty studies involving a combined total of 2075 participants were ultimately incorporated. It was observed that the combination of EDA with HBOT for the treatment of DEACMP demonstrated an improvement in the total effective rate (RR: 1.25; 95 % CI: 1.20-1.31; P < 0.01), MMSE (WMD: 3.67; 95 % CI: 2.59-4.76; P < 0.01), MoCA (WMD: 4.38; 95 % CI: 4.00-4.76; P < 0.01), BI (WMD: 10.94; 95 % CI: 5.23-16.66; P < 0.01), HDS (WMD: 6.80; 95 % CI: 4.05-9.55; P < 0.01), FMA (WMD: 8.91; 95 % CI: 7.22-10.60; P < 0.01), SOD (WMD: 18.45; 95 % CI: 16.93-19.98; P < 0.01); and a reduction in NIHSS (WMD: -4.12; 95 % CI: -4.93 to -3.30; P < 0.01) and MDA (WMD: -3.05; 95 % CI: -3.43 to -2.68; P < 0.01).
CONCLUSIONS: Low-quality evidence suggests that for DEACMP, compared to using HBOT alone, the combined use of EDA and HBOT may be associated with better cognition and activity of daily living. In the future, conducting more meticulously designed multicenter and large-sample RCTs to substantiate our conclusions is essential.

UNASSIGNED: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that influences structures of ectodermal origin, such as teeth, hair, and sweat glands. Compared with autosomal recessive and dominant modes of inheritance, the X-linked HED (XLHED) characterized by Hypodontia/Oligodontia teeth, Absent/sparse hair, Anhidrosis/hypohidrosis, and characteristic facial features, is the most frequent and its primary cause is the mutation of ectodysplasin A (EDA) gene. This research aimed to expound the clinical and molecular features of a Chinese male with XLHED and to summarize and compare several previous findings.
UNASSIGNED: Genomic DNA was obtained from the peripheral blood of the proband and his family members, then Sanger sequencing was used to perform a mutational analysis of EDA. Real-time quantitative PCR and Western blotting were used to detect EDA expression. The transcriptional activity of NF-κB was detected using a luciferase assay.
UNASSIGNED: The probandwith XLHED was identified a novel EDA mutation, c.1119G>C(p.M373I), that affected the molecular analysis of transmembrane protein exon8 mutations, inherited from the mother. He showed a severe multiple-tooth loss, with over 20 permanent teeth missing and sparse hair and eyebrows, dry, thin, and itching skin. Furthermore, his sweating function was abnormal to a certain extent.
UNASSIGNED: The functional study showed that this novel mutant led to a significant decrease in the EDA expression level and transcriptional activity of NF-κB. Our findings extend the range of EDA mutations in XLHED patients, which provides the basis and idea for further exploring the pathogenesis of XLHED.

Assessing drivers\' mental workload is crucial for reducing road accidents. This study examined drivers\' mental workload in a simulated auditory-based dual-task driving scenario, with driving tasks as the main task, and auditory-based N-back tasks as the secondary task. A total of three levels of mental workload (i.e., low, medium, high) were manipulated by varying the difficulty levels of the secondary task (i.e., no presence of secondary task, 1-back, 2-back). Multimodal measures, including a set of subjective measures, physiological measures, and behavioral performance measures, were collected during the experiment. The results showed that an increase in task difficulty led to increased subjective ratings of mental workload and a decrease in task performance for the secondary N-back tasks. Significant differences were observed across the different levels of mental workload in multimodal physiological measures, such as delta waves in EEG signals, fixation distance in eye movement signals, time- and frequency-domain measures in ECG signals, and skin conductance in EDA signals. In addition, four driving performance measures related to vehicle velocity and the deviation of pedal input and vehicle position also showed sensitivity to the changes in drivers\' mental workload. The findings from this study can contribute to a comprehensive understanding of effective measures for mental workload assessment in driving scenarios and to the development of smart driving systems for the accurate recognition of drivers\' mental states.

OBJECTIVE: Tooth agenesis is a common craniofacial malformation, which is often associated with gene mutations. The purpose of this research was to investigate and uncover ectodysplasin A (EDA) gene variants in eight Chinese families affected with tooth agenesis.
METHODS: Genomic DNA was extracted from tooth agenesis families and sequenced using whole-exome sequencing. The expression of ectodysplasin A1 (EDA1) protein was studied by western blot, binding activity with receptor was tested by pull-down and the NF-κB transcriptional activity was analyzed by Dual luciferase assay.
RESULTS: Eight EDA missense variants were discovered, of which two (c.T812C, c.A1073G) were novel. The bioinformatics analysis indicated that these variants might be pathogenic. The tertiary structure analysis revealed that these eight variants could cause structural damage to EDA proteins. In vitro functional studies demonstrated that the variants greatly affect protein stability or impair the EDA-EDAR interaction; thereby significantly affecting the downstream NF-κb transcriptional activity. In addition, we summarized the genotype-phenotype correlation caused by EDA variants and found that EDA mutations leading to NSTA are mostly missense mutations located in the TNF domain.
CONCLUSIONS: Our results broaden the variant spectrum of the EDA gene associated with tooth agenesis and provide valuable information for future genetic counseling.

BACKGROUND: The aim of this study was to analyse the differences in the phenotypes of missing teeth between a pair of brothers with hypohidrotic ectodermal dysplasia (HED) and to investigate the underlying mechanism by comparing the mutated gene loci between the brothers with whole-exome sequencing.
METHODS: The clinical data of the patients and their mother were collected, and genomic DNA was extracted from peripheral blood samples. By Whole-exome sequencing filtered for a minor allele frequency (MAF) ≤0.05 non-synonymous single-nucleotide variations and insertions/deletions variations in genes previously associated with tooth agenesis, and variations considered as potentially pathogenic were assessed by SIFT, Polyphen-2, CADD and ACMG. Sanger sequencing was performed to detect gene variations. The secondary and tertiary structures of the mutated proteins were predicted by PsiPred 4.0 and AlphaFold 2.
RESULTS: Both brothers were clinically diagnosed with HED, but the younger brother had more teeth than the elder brother. An EDA variation (c.878 T > G) was identified in both brothers. Additionally, compound heterozygous variations of WNT10A (c.511C > T and c.637G > A) were identified in the elder brother. Digenic variations in EDA (c.878 T > G) and WNT10A (c.511C > T and c.637G > A) in the same patient have not been reported previously. The secondary structure of the variant WNT10A protein showed changes in the number and position of α-helices and β-folds compared to the wild-type protein. The tertiary structure of the WNT10A variant and molecular simulation docking showed that the site and direction where WNT10A binds to FZD5 was changed.
CONCLUSIONS: Compound heterozygous WNT10A missense variations may exacerbate the number of missing teeth in HED caused by EDA variation.

UNASSIGNED: To analyse the pathogenic genes in a patient with hypohidrotic ectodermal dysplasia (HED) and explore the relationship between pathogenic genes and the oligodontia phenotype.
UNASSIGNED: Clinical data and peripheral blood were collected from a patient with HED. Pathogenic genes were analysed by whole-exon sequencing (WES) and verified by Singer sequencing. The secondary and tertiary structures of the variant proteins were predicted to analyse their toxicity.
UNASSIGNED: The patient exhibited a severe oligodontia phenotype, wherein only two deciduous canines were left in the upper jaw. WES revealed a hemizygous EDA variant c.466C > T p.(Arg156Cys) and a novel heterozygous EVC2 variant c.1772T > C p.(Leu591Ser). Prediction of the secondary and tertiary structures of the EDA variant p.(Arg156Cys) and EVC2 variant p.(Leu591Ser) indicated impaired function of both molecules.
UNASSIGNED: The patient demonstrated a more severe oligodontia phenotype when compared with the other patients caused by the EDA variant c.466C > T. Since Evc2 is a positive regulator of the Sonic Hedgehog (Shh) signal pathway, we speculated that the EVC2 variant p.(Leu591Ser) may play a synergistic role in the oligodontia phenotype of HED, thereby exacerbating the oligodontia phenotype. Knowledge of oligodontia caused by multiple gene variants is of great significance for understanding individual differences in oligodontia phenotypes.

It has been demonstrated that odors could affect humans at the psychophysiological level. Significant research has been done on odor perception and physiological mechanisms; however, this research was mainly performed in highly controlled conditions in order to highlight the perceptive phenomena and the correlated physiological responses in the time frame of milliseconds. The present study explored how human physiological activity evolves in response to different odor conditions during an ecological olfactory experience on a broader time scale (from 1 to 90 s). Two odors, vanilla and menthol, together with a control condition (blank) were employed as stimuli. Electroencephalographic (EEG) activity in four frequency bands of interest, theta, alpha, low beta, and high beta, and the electrodermal activity (EDA) of the skin conductance level and response (SCL and SCR) were investigated at five time points taken during: (i) the first ten seconds of exposure (short-term analysis) and (ii) throughout the entire exposure to each odor (90 s, long-term analysis). The results revealed significant interactions between the odor conditions and the time periods in the short-term analysis for the overall frontal activity in the theta (p = 0.03), alpha (p = 0.005), and low beta (p = 0.0067) bands, the frontal midline activity in the alpha (p = 0.015) and low beta (p = 0.02) bands, and the SCR component (p = 0.024). For the long-term effects, instead, only one EEG parameter, frontal alpha asymmetry, was significantly sensitive to the considered dimensions (p = 0.037). In conclusion, the present research determined the physiological response to different odor conditions, also demonstrating the sensitivity of the employed parameters in characterizing the dynamic of such response during the time. As an exploratory study, this work points out the relevance of considering the effects of continuous exposure instead of short stimulation when evaluating the human olfactory experience, providing insights for future studies in the field.

An ethylenediamine (EDA) gas sensor based on a composite of MoO3 nanoribbon and reduced graphene oxide (rGO) was fabricated in this work. MoO3 nanoribbon/rGO composites were synthesized using a hydrothermal process. The crystal structure, morphology, and elemental composition of MoO3/rGO were analyzed via XRD, FT-IR, Raman, TEM, SEM, XPS, and EPR characterization. The response value of MoO3/rGO to 100 ppm ethylenediamine was 843.7 at room temperature, 1.9 times higher than that of MoO3 nanoribbons. The MoO3/rGO sensor has a low detection limit (LOD) of 0.235 ppm, short response time (8 s), good selectivity, and long-term stability. The improved gas-sensitive performance of MoO3/rGO composites is mainly due to the excellent electron transport properties of graphene, the generation of heterojunctions, the higher content of oxygen vacancies, and the large specific surface area in the composites. This study presents a new approach to efficiently and selectively detect ethylenediamine vapor with low power.

BACKGROUND: Ectodysplasin-A (EDA), a skin-specific TNF ligand, interacts with its membrane receptor EDAR to trigger EDA signaling in skin appendage formation. Gene mutations in EDA signaling cause Anhidrotic/Hypohidrotic Ectodermal Dysplasia (A/HED), which affects the formation of skin appendages including hair, teeth, and several exocrine glands.
RESULTS: We report that EDA triggers the translocation of its receptor EDAR from a cytosolic compartment into the plasma membrane. We use protein affinity purification to show that upon EDA stimulation EDAR associates with SNAP23-STX6-VAMP1/2/3 vesicle trafficking complexes. We find that EDA-dependent PKA activation is critical for the association. Notably, either of two HED-linked EDAR mutations, T346M and R420W, prevents EDA-induced EDAR translocation; and both EDA-induced PKA activation and SNAP23 are required for Meibomian gland (MG) growth in a skin appendage model.
CONCLUSIONS: Overall, in a novel regulatory mechanism, EDA increases plasma membrane translocation of its own receptor EDAR, augmenting EDA-EDAR signaling in skin appendage formation. Our findings also provide PKA and SNAP23 as potential targets for the intervention of HED.

Non-syndromic tooth agenesis (NSTA) is one of the most common dental developmental malformations affected by genetic factors predominantly. Among all 36 candidate genes reported in NSTA individuals, EDA, EDAR, and EDARADD play essential roles in ectodermal organ development. As members of the EDA/EDAR/NF-κB signaling pathway, mutations in these genes have been implicated in the pathogenesis of NSTA, as well as hypohidrotic ectodermal dysplasia (HED), a rare genetic disorder that affects multiple ectodermal structures, including teeth. This review provides an overview of the current knowledge on the genetic basis of NSTA, with a focus on the pathogenic effects of the EDA/EDAR/NF-κB signaling pathway and the role of EDA, EDAR, and EDARADD mutations in developmental tooth defects. We also discuss the phenotypic overlap and genetic differences between NSTA and HED. Ultimately, this review highlights the importance of genetic analysis in diagnosing and managing NSTA and related ectodermal disorders, and the need for ongoing research to improve our understanding of these conditions.