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Purpose: This study evaluated medical students' knowledge and attitudes toward epilepsy and the influence of metacognition thereon., Method: Valid questionnaires were administered to medical students including undergraduate, professional postgraduate, and standardized residency training students (N = 503). The questionnaire had 4 parts: demographic information, knowledge of epilepsy, attitudes toward epilepsy, and metacognitive assessment. The Chinese Public Attitudes Toward Epilepsy scale and 30-Item Metacognition Questionnaire were used to assess attitudes and metacognition, respectively., Results: Almost all participants had heard of epilepsy; 38.8% had witnessed a seizure and 25% were acquainted with a person with epilepsy. The proportion of correct answers to epilepsy-related knowledge ranged from 40.6% (Putting an object into the mouth of a person experiencing an epileptic seizure) to 97% (Convulsion is a symptom of epilepsy). However, knowledge of epilepsy was not able to affect attitudes toward epilepsy. Age, years of clinical experience, having witnessed a seizure, positive belief of worry, and need to control thinking were correlated with the different domains of attitude toward epilepsy. When participants were divided into 2 groups-i.e., those with high and low knowledge of epilepsy, participants in the former group who had a positive belief of worry or had not witnessed any seizures were more likely to have negative attitudes toward epilepsy., Conclusion: Medical students showed good awareness of the etiology and symptoms of epilepsy. Overall, attitudes toward epilepsy were negative. A positive belief of worry was associated with a more negative attitude toward epilepsy among respondents with greater knowledge of epilepsy., 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 © 2023 Elsevier Inc. All rights reserved.)

Recently, increased production and consumption of disinfectants such as triclosan (TCS) and triclocarban (TCC) have led to massive pollution of the environment, which draws global concern over the potential risk to aquatic organisms. However, the olfactory toxicity of disinfectants in fish remains elusive to date. In the present study, the impact of TCS and TCC on the olfactory capacity of goldfish was assessed by neurophysiological and behavioral approaches. As shown by the reduced distribution shifts toward amino acid stimuli and hampered electro-olfactogram responses, our results demonstrated that TCS/TCC treatment would cause deterioration of the olfactory ability of goldfish. Our further analysis found that TCS/TCC exposure suppressed the expression of olfactory G protein-coupled receptors in the olfactory epithelium, restricted the transformation of odorant stimulation into electrical responses by disturbing the cAMP signaling pathway and ion transportation, and induced apoptosis and inflammation in the olfactory bulb. In conclusion, our results demonstrated that an environmentally realistic level of TCS/TCC would weaken the olfactory capacity of goldfish by constraining odorant recognition efficiency, disrupting olfactory signal generation and transduction, and disturbing olfactory information processing., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: Environmental pollution may give rise to the incidence and progression of nonalcoholic fatty liver disease (NAFLD), the most common cause for chronic severe liver lesions. Although knowledge of NAFLD pathogenesis is particularly important for the development of effective prevention, the relationship between NAFLD occurrence and exposure to emerging pollutants, such as microplastics (MPs) and antibiotic residues, awaits assessment., Objectives: This study aimed to evaluate the toxicity of MPs and antibiotic residues related to NAFLD occurrence using the zebrafish model species., Methods: Taking common polystyrene MPs and oxytetracycline (OTC) as representatives, typical NAFLD symptoms, including lipid accumulation, liver inflammation, and hepatic oxidative stress, were screened after 28-d exposure to environmentally realistic concentrations of MPs ( 0.69 mg / L ) and antibiotic residue ( 3.00 μ g / L ). The impacts of MPs and OTC on gut health, the gut-liver axis, and hepatic lipid metabolism were also investigated to reveal potential affecting mechanisms underpinning the NAFLD symptoms observed., Results: Compared with the control fish, zebrafish exposed to MPs and OTC exhibited significantly higher levels of lipid accumulation, triglycerides, and cholesterol contents, as well as inflammation, in conjunction with oxidative stress in their livers. In addition, a markedly smaller proportion of Proteobacteria and higher ratios of Firmicutes/Bacteroidetes were detected by microbiome analysis of gut contents in treated samples. After the exposures, the zebrafish also experienced intestinal oxidative injury and yielded significantly fewer numbers of goblet cells. Markedly higher levels of the intestinal bacteria-sourced endotoxin lipopolysaccharide (LPS) were also detected in serum. Animals treated with MPs and OTC exhibited higher expression levels of LPS binding receptor ( LBP ) and downstream inflammation-related genes while also exhibiting lower activity and gene expression of lipase. Furthermore, MP-OTC coexposure generally exerted more severe effects compared with single MP or OTC exposure., Discussion: Our results suggested that exposure to MPs and OTC may disrupt the gut-liver axis and be associated with NAFLD occurrence. https://doi.org/10.1289/EHP11600.

Although accumulating data demonstrated that gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, plays an important regulatory role in immunity of vertebrates, its immunomodulatory function and mechanisms of action remain poorly understood in invertebrates such as bivalve mollusks. In this study, the effect of GABA on phagocytic activity of hemocytes was evaluated in a commercial bivalve species, Tegillarca granosa. Furthermore, the potential regulatory mechanism underpinning was investigated by assessing potential downstream targets. Data obtained demonstrated that in vitro GABA incubation significantly constrained the phagocytic activity of hemocytes. In addition, the GABA-induced suppression of phagocytosis was markedly relieved by blocking of GABA A and GABA B receptors using corresponding antagonists. Hemocytes incubated with lipopolysaccharides (LPS) and GABA had significant higher K + -Cl - cotransporter 2 (KCC2) content compared to the control. In addition, GABA treatment led to an elevation in intracellular Cl - , which was shown to be leveled down to normal by blocking the ionotropic GABA A receptor. Treatment with GABA A receptor antagonist also rescued the suppression of GABA A receptor-associated protein (GABARAP), KCC, TNF receptor associated factor 6 (TRAF6), inhibitor of nuclear factor kappa-B kinase subunit alpha (IKKα), and nuclear factor kappa B subunit 1 (NFκB) caused by GABA incubation. Furthermore, incubation of hemocytes with GABA resulted in a decrease in cAMP content, an increase in intracellular Ca 2+ , and downregulation of cAMP-dependent protein kinase (PKA), calmodulin kinase II (CAMK2), calmodulin (CaM), calcineurin (CaN), TRAF6, IKKα, and NFκB. All these above-mentioned changes were found to be evidently relieved by blocking the metabotropic G-protein-coupled GABA B receptor. Our results suggest GABA may play an inhibitory role on phagocytosis through binding to both GABA A and GABA B receptors, and subsequently regulating corresponding downstream pathways in bivalve invertebrates., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: Uniconazole is an effective plant growth regulator that can be used in banana cultivation to promote dwarfing and enhance lodging resistance. However, the mechanisms underlying banana dwarfing induced by uniconazole are unknown. In uniconazole-treated bananas, gibberellin (GA) was downregulated compared to the control groups. An integrative analysis of transcriptomes and metabolomes was performed on dwarf bananas induced by uniconazole and control groups. The key pathways involved in uniconazole-induced dwarfism in banana were determined according to the overlap of KEGG annotation of differentially expressed genes and (DEGs) differential abundant metabolites (DAMs)., Results: Compared with the control groups, the levels of some flavonoids, tannins, and alkaloids increased, and those of most lipids, amino acids and derivatives, organic acids, nucleotides and derivatives, and terpenoids decreased in uniconazole-treated bananas. Metabolome analysis revealed the significant changes of flavonoids in uniconazole-treated bananas compared to control samples at both 15 days and 25 days post treatment. Transcriptome analysis shows that the DEGs between the treatment and control groups were related to a series of metabolic pathways, including lignin biosynthesis, phenylpropanoid metabolism, and peroxidase activity. Comprehensive analysis of the key pathways of co-enrichment of DEGs and DAMs from 15 d to 25 d after uniconazole treatment shows that flavonoid biosynthesis was upregulated., Conclusions: In addition to the decrease in GA, the increase in tannin procyanidin B1 may contribute to dwarfing of banana plants by inhibiting the activity of GA. The increased of flavonoid biosynthesis and the change of lignin biosynthesis may lead to dwarfing phenotype of banana plants. This study expands our understanding of the mechanisms underlying uniconazole-induced banana dwarfing., (© 2022. The Author(s).)

The natural compound, exopolysaccharide from Lactobacillus casei NA-2 (EPS-cn2), has been shown to inhibit biofilm formation by Escherichia coli O157:H7. Although bacterial adhesion to substrate surfaces is a primary, indispensable step in this process, the mechanisms by which EPS-cn2 can block E. coli O157:H7 adhesion to biotic or abiotic surfaces remain unclear. In this study, investigation of E. coli O157:H7 response to EPS-cn2 revealed that 1 mg/mL EPS-cn2 can decrease adherence to polystyrene and confluent Caco-2 cell surfaces to 49.0% (P＜0.0001) and 57.0% (P＜0.01) of that in untreated E. coli O157:H7, respectively. Moreover, EPS-cn2 significantly reduced outer membrane hydrophobicity by 49.0% and decreased the electronegativity of the membrane surface charge by as much as 1.57 mV (P＜0.05) compared to untreated cells. High throughput RNA sequencing indicated that genes responsible for adhesion through extracellular matrix secretion, such as poly-N-acetyl-glucosamine (PNAG) biosynthesis, locus of enterocyte effacement (LEE) proteins and outer membrane protein (OmpT) were all down-regulated in response to EPS-cn2, while chemotaxis and motility-related flagellar assembly genes were differentially up-regulated, suggesting that the EPS-cn2 may serve as an extracellular signal to attenuate adhesion-related gene expression and alter bacterial surface properties in E. coli O157:H7. These findings support the further development of EPS-cn2 for pathogenic biofilm management in clinical and industrial settings, and suggests the further targeting of adhesion-related genes to limit the persistence of this highly pathogenic strain in sensitive environments., 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 Elsevier Ltd. All rights reserved.)

Background: Stroke is one of the major challenges for the global healthcare system, which makes it necessary to explore the relationship between various modifiable factors and stroke risk. Recently, numerous meta-analyses of prospective observational studies have reported that dietary factors played a key role in the occurrence of stroke. However, the conclusions of previous studies have remained controversial and unclear. Accordingly, we conducted an umbrella review synthesizing and recalculating available evidence to assess the certainty of the associations between dietary factors and stroke., Methods: Relevant meta-analyses examining the associations between dietary factors and stroke were searched in PubMed and Embase databases up to September 1, 2021. For each eligible meta-analysis, two independent reviewers appraised the methodologic quality using the AMSTAR 2 criteria and estimated the summary effect size, 95% confidence intervals, 95% prediction intervals, heterogeneity between studies, and small-study effects. Moreover, we further assessed the associations between dietary factors and ischemic stroke as well as hemorrhagic stroke. Lastly, a set of pre-specified criteria was applied to qualitatively evaluate the epidemiological credibility of each dietary factor., Results: Overall, our umbrella review included 122 qualified meta-analyses for qualitative synthesis, involving 71 dietary factors related to food groups, foods, macronutrients, and micronutrients. Using the AMSTAR 2 criteria, 5 studies were assessed as high quality, 4 studies as moderate quality, and 113 studies as low or critically low quality. We identified 34 dietary factors associated with stroke occurrence, 25 dietary factors related to ischemic stroke, and 11 factors related to hemorrhagic stroke. Among them, high/moderate certainty epidemiological evidence demonstrated an inverse association between intake of fruits (RR: 0.90) and vegetables (RR: 0.92) and stroke incidence, but a detrimental association between red meat (RR: 1.12), especially processed red meat consumption (RR:1.17), and stroke incidence. Besides, the evidence of high/moderate certainty suggested that the intake of processed meat, fruits, coffee, tea, magnesium, and dietary fiber was associated with ischemic stroke risk, while consumption of tea, fruits, and vegetables was relevant to hemorrhagic stroke susceptibility., Conclusions: Our study has reported that several dietary factors have a significant impact on stroke risk and offered a new insight into the relationship between dietary modification and stroke occurrence. Our results may provide an effective strategy for stroke prevention., (© 2022. The Author(s).)

N 6 -Methyladenosine (m 6 A) methylation is the most abundant post-transcription modification in eukaryotes and plays a vital role in many pathological conditions including cerebral ischemia-reperfusion injury and vascular inflammation. Moreover, recent studies have reported that single-nucleotide polymorphisms (SNPs) can affect the m 6 A modification. Therefore, we investigated the relationship between m 6 A-SNPs and ischemic stroke (IS) risk through integrative analysis of an IS genome-wide association study and m 6 A-SNP list from the m6AVar database. Next, we performed eQTL and differential expression analysis to support these IS-associated m 6 A-SNPs. Finally, using the identified polymorphisms, a PPI network was constructed using the STRING database, and GO and pathway enrichment analyses were performed using the DAVID online tool. Accordingly, we identified 305 IS-associated SNPs that could affect m 6 A methylation. Next, 158 of these SNPs were determined to have eQTL signals on local genes. We further identified 84 local genes (containing a total of 87 SNPs) that were differentially expressed in IS patients. Finally, we identified several biological processes and pathways related to IS pathogenesis, such as "leukocyte migration" and "focal adhesion." In summary, our study detected dozens of m 6 A-SNPs as critical functional polymorphisms and novel genetic biomarkers for IS susceptibility and provided a new means of elucidating the biological mechanism underlying IS development., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

The angiopoietin-like protein (ANGPTL) family members, except for the novel atypical member ANGPTL8/betatrophin, have been reported to participate in angiogenesis, inflammation and cancer. ANGPTL8/betatrophin is a metabolic regulator that is involved in lipid metabolism and glucose homeostasis. However, little is known about the expression and prognostic value of ANGPTL8/betatrophin in human cancers. In this study, we first conducted detailed analyses of ANGPTL8/betatrophin expression in cancer/normal samples via the Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), DriverDBv3, ENCORI and UALCAN databases. ANGPTL8/betatrophin showed high tissue specificity (enriched in the liver) and cell-type specificity (enriched in HepG2 and MCF7 cell lines). More than one databases demonstrated that the gene expression of ANGPTL8/betatrophin was significantly lower in cholangiocarcinoma (CHOL), breast invasive carcinoma (BRCA), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), uterine corpus endometrial carcinoma (UCEC), and significantly higher in kidney renal clear cell carcinoma (KIRC) compared with that in normal samples. However, the protein expression of ANGPTL8/betatrophin displayed opposite results in clear cell renal cell carcinoma (ccRCC)/KIRC. Based on the expression profiles, the prognostic value was evaluated with the GEPIA, DriverDBv3, Kaplan Meier plotter and ENCORI databases. Two or more databases demonstrated that ANGPTL8/betatrophin significantly affected the survival of KIRC, uterine corpus endometrial carcinoma (UCEC), pheochromocytoma and paraganglioma (PCPG) and sarcoma (SARC); patients with PCPG and SARC may benifit from high ANGPTL8/betatrophin expression while high ANGPTL8/betatrophin expression was associated with poor prognosis in KIRC and UCEC. Functional analyses with the GeneMANIA, Metascape and STRING databases suggested that ANGPTL8/betatrophin was mainly involved in lipid homeostasis, especially triglyceride and cholesterol metabolism; glucose homeostasis, especially insulin resistance; AMPK signaling pathway; PI3K/Akt signaling pathway; PPAR signaling pathway; mTOR signaling pathway; HIF-1 signaling pathway; autophagy; regulation of inflammatory response. ANGPTL8/betatrophin may be a promising prognostic biomarker and therapeutic target, thus providing evidence to support further exploration of its role in defined human cancers., 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 © 2021 Xu, Tian, Shi, Sun and Chen.)

In the past decade, an increasing number of genome-wide association studies (GWASs) have been applied to ischemic stroke (IS) susceptibility and recovery. In our study, six GWAS-linked hot loci ( ALDH2 rs10744777, HDAC9 rs2107595, ABO rs532436, PATJ rs76221407, LOC105372028 rs1842681 and PTCH1 rs2236406) were selected, genotyped and analyzed in 982 IS patients from northern Chinese population, in order to explore their roles in stroke functional outcome and recurrence risk. We found that PTCH1 rs2236406 was significantly associated with functional outcome after stroke. Further logistic regression analysis revealed the variant genotype TC/CC of rs2236406 as an independent prognostic factor for poor stroke recovery in Chinese population. Meanwhile, we observed that GA/AA genotype of ABO rs532436 was statistically correlated with the increased risk of stroke recurrence, especially for patients with large-artery atherosclerosis. Moreover, multivariate Cox analysis identified ABO rs12342 as an independent predictor for IS recurrence. Further functional annotation analysis demonstrated that rs2236406 and rs2043211 were located in the transcriptionally active region, and could change the regulatory motif, transcription factor binding capacity and expression level of RP11-435O5.5 (antisense to PTCH1) and ABO, respectively. In summary, our results suggested that PTCH1 rs2236406 and ABO rs532436 may be novel genetic markers and potential therapeutic targets for stroke prognosis. More studies are required to confirm our findings and clarify the underlying molecular mechanisms., Competing Interests: None., (AJTR Copyright © 2021.)

With the successful establishment of both targeted gene disruption and integration methods in the true diploid frog Xenopus tropicalis, this excellent vertebrate genetic model now is making a unique contribution to modelling human diseases. Here, we summarize our efforts on establishing homologous recombination-mediated targeted integration in Xenopus tropicalis, the usefulness, and limitation of targeted integration via the homology-independent strategy, and future directions on how to further improve targeted gene integration in Xenopus tropicalis., (© 2017 Wiley Periodicals, Inc.)