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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 lg/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, Introduction Nonalcoholic fatty liver disease (NAFLD), characterized by excessive fat accumulation in hepatocytes, was suggested to be the most common cause of chronic liver lesions. (1) Recent surveys have demonstrated [...]

Potato common scab, an economically important disease worldwide, is caused by pathogenic Streptomyces strains mainly through the effects of thaxtomin. The cello-oligosaccharides binding protein CebE is proposed as a gateway to the pathogenic development of Streptomyces scabiei. In this study, two functional CebE encoding genes, GEO5601 and GEO7671, were identified in pathogenic Streptomyces sp. AMCC400023. With a higher binding affinity towards signal molecules, the deletion of GEO5601 severely impaired thaxtomin-producing capacity and reduced the strain's pathogenicity. Transcriptional analysis confirmed that CebE5601 is also responsible for the import and provision of carbon sources for cell growth. With lower binding affinity, the pathogenicity island (PAI)-localized CebE7671 may assume a new function of mediating the biological process of sporulation, given the significantly impaired formation of ΔGEO7671 spores. The mechanisms of action of CebE proteins unraveled in Streptomyces sp. AMCC400023 will help pave the way for more effective prevention of the potato common scab disease. [ABSTRACT FROM AUTHOR]

In recent years, traditional antibiotic efficacy outcomes have rapidly diminished due to the advent of drug resistance, and the dose limitation value has increased due to the severe side effect of globalized healthcare. Therefore, novel strategies are required to resensitize resistant pathogens to antibiotics existing in the field and prevent the emergence of drug resistance. In this study, cationic hyperbranched polylysine (HBPL-6) was synthesized using the one-pot polymerization method. HBPL-6 exhibited excellent non-cytotoxicity and bio-solubility properties. The present study also showed that HBPL-6 altered the outer membrane (OM) integrity of Escherichia coli O157:H7, Salmonella typhimurium, and Pseudomonas aeruginosa PAO1 by improving their permeability levels. When administered at a safe dosage, HBPL-6 enhanced the accumulation of rifampicin (RIF) and erythromycin (ERY) in bacteria to restore the efficacy of the antibiotics used. Moreover, the combination of HBPL-6 with colistin (COL) reduced the antibiotic dosage, which was helpful in preventing further drug-resistance outcomes. Therefore, this research provides a new strategy for reducing the dosage of drugs used to combat Gram-negative (G−) bacteria through their synergistic effects. [ABSTRACT FROM AUTHOR]

Aims: Disturbances in the circadian rhythm are positively correlated with the processes of aging and related neurodegenerative diseases, which are also associated with brain iron accumulation. However, the role of brain iron in regulating the biological rhythm is poorly understood. In this study, we investigated the impact of brain iron levels on the spontaneous locomotor activity of mice with altered brain iron levels and further explored the potential mechanisms governing these effects in vitro. Results: Our results revealed that conditional knockout of ferroportin 1 (Fpn1) in cerebral microvascular endothelial cells led to brain iron deficiency, subsequently resulting in enhanced locomotor activity and increased expression of clock genes, including the circadian locomotor output cycles kaput protein (Clock) and brain and muscle ARNT‐like 1 (Bmal1). Concomitantly, the levels of period circadian regulator 1 (PER1), which functions as a transcriptional repressor in regulating biological rhythm, were decreased. Conversely, the elevated brain iron levels in APP/PS1 mice inhibited autonomous rhythmic activity. Additionally, our findings demonstrate a significant decrease in serum melatonin levels in Fpn1cdh5 ‐CKO mice compared with the Fpn1flox/flox group. In contrast, APP/PS1 mice with brain iron deposition exhibited higher serum melatonin levels than the WT group. Furthermore, in the human glioma cell line, U251, we observed reduced PER1 expression upon iron limitation by deferoxamine (DFO; iron chelator) or endogenous overexpression of FPN1. When U251 cells were made iron‐replete by supplementation with ferric ammonium citrate (FAC) or increased iron import through transferrin receptor 1 (TfR1) overexpression, PER1 protein levels were increased. Additionally, we obtained similar results to U251 cells in mouse cerebellar astrocytes (MA‐c), where we collected cells at different time points to investigate the rhythmic expression of core clock genes and the impact of DFO or FAC treatment on PER1 protein levels. Conclusion: These findings collectively suggest that altered iron levels influence the circadian rhythm by regulating PER1 expression and thereby modulating the molecular circadian clock. In conclusion, our study identifies the regulation of brain iron levels as a potential new target for treating age‐related disruptions in the circadian rhythm. [ABSTRACT FROM AUTHOR]

Nonpharmaceutical interventions (NPIs) for coronavirus disease 2019 (COVID‐19) not only reduce the prevalence of this disease among children but also influence the transmission of other viruses. This retrospective study investigated the impact of NPIs on human enterovirus (HEV) infection in children diagnosed with hand, foot, and mouth disease (HFMD) or herpangina (HA) in Hangzhou, China. We collected and analyzed the laboratory results and clinical data of children diagnosed with HFMD or HA during the following periods: pre‐COVID‐19 (January 2019 to December 2019), the COVID‐19 pandemic (January 2020 to December 2022), and post‐COVID‐19 (January to December 2023). A total of 41 742 specimens that met the inclusion criteria were obtained, of which 1998 (4.79%) tested positive for enterovirus. In comparison to those in the pre‐COVID‐19 period, which had 695 (5.63%) HEV‐positive specimens, the numbers dramatically decreased to 69 (1.19%), 398 (5.12%), and 112 (1.58%) in 2020, 2021, and 2022, respectively, but significantly increased to 724 (8.27%) in 2023. Seasonal peaks of infections occurred in May, June, July, and August each year, with the total detection rate ranging from 2019 to 2023 being 9.41% in May, 22.47% in June, 28.23% in July, and 12.16% in August, respectively. The difference in the detection rates of HEV infection between males and females was statistically significant (p < 0.005), with 5.11% (1221/23 898) of males and 4.35% (777/17 844) of females testing positive, resulting in a male‐to‐female positive ratio of 1.57:1. Among the age groups, 11.25% (378/3360) of the children aged 3–5 years had the highest detection rate, which steadily decreased with increasing or decreasing age. The detection of HEV indicated that >95% of the viruses were other types than the previously commonly reported enterovirus 71 (EV‐A71) and coxsackievirus A16 (CV‐A16). In conclusion, NPIs for COVID‐19 may be effective at reducing the transmission of HEV. However, with the relaxation of NPIs, the detection rate of HEVs increased slowly to a certain extent. Active awareness and surveillance of the epidemiological characteristics of HEV are essential for preventing, controlling, and managing the development of HFMD and HA, as well as contributing to the development of a multivalent HFMD vaccine. [ABSTRACT FROM AUTHOR]

In this study, D-mannose was used to synthesize poly-D-mannose using a one-pot method. The molecular weight, degree of branching, monosaccharide composition, total sugar content, and infrared spectrum were determined. In addition, we evaluated the safety and bioactivity of poly-D-mannose including anti-pathogen biofilm, antioxidant, and anti-inflammatory activity. The results showed that poly-D-mannose was a mixture of four components with different molecular weights. The molecular weight of the first three components was larger than 410,000 Da, and that of the fourth was 3884 Da. The branching degree of poly-D-mannose was 0.53. The total sugar content was 97.70%, and the monosaccharide was composed only of mannose. The infrared spectra showed that poly-D-mannose possessed characteristic groups of polysaccharides. Poly-D-mannose showed no cytotoxicity or hemolytic activity at the concentration range from 0.125 mg/mL to 8 mg/mL. In addition, poly-D-mannose had the best inhibition effect on Salmonella typhimurium at the concentration of 2 mg/mL (68.0% ± 3.9%). The inhibition effect on Escherichia coli O157:H7 was not obvious, and the biofilm was reduced by 37.6% ± 2.9% at 2 mg/mL. For Staphylococcus aureus and Bacillus cereus, poly-D-mannose had no effect on biofilms at low concentration; however, 2 mg/mL of poly-D-mannose showed inhibition rates of 33.7% ± 6.4% and 47.5% ± 4%, respectively. Poly-D-mannose showed different scavenging ability on free radicals. It showed the best scavenging effect on DPPH, with the highest scavenging rate of 74.0% ± 2.8%, followed by hydroxyl radicals, with the scavenging rate of 36.5% ± 1.6%; the scavenging rates of superoxide anion radicals and ABTS radicals were the lowest, at only 10.1% ± 2.1% and 16.3% ± 0.9%, respectively. In lipopolysaccharide (LPS)-stimulated macrophages, poly-D-mannose decreased the secretion of nitric oxide (NO) and reactive oxygen species (ROS), and down-regulated the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Therefore, it can be concluded that poly-D-mannose prepared in this research is safe and has certain biological activity. Meanwhile, it provides a new idea for the development of novel prebiotics for food and feed industries or active ingredients used for pharmaceutical production in the future. [ABSTRACT FROM AUTHOR]