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Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder in school-age children and adolescents. However, the reported associations between ADHD and single nutrient intake are inconsistent. The aim of the study was to investigate the relationships between dietary intake changes and the prevalence of ADHD over time with repeat measurements using data from the Children Health and Environment Research (CHEER). To assess changes over time, we used data obtained in 2006 and 2008 (Phases 1 and 2). In this study, there were 2899 children aged 8 years or older in Phase 1 and 2120 children aged 9 years or older in Phase 2 from Korea, and the ADHD scores and dietary intake of 1733 children in Phases 1 and 2 were used in the final analysis. The YN group refers to children whose disease had improved in Phase 2, and the NY group refers to children diagnosed with ADHD in Phase 2. A notable within-group result was the increase in vegetable protein (p = 0.03) in the YN group. A between-group comparison showed that significant changes in nutrient intake could be confirmed most in the NY group, and the YN group tended to have a lower nutrient intake than the NY group. In the correlation of changes in nutrient intake and three subtypes (combined, AD, and HD), the total fat (p = 0.048) and animal protein (p = 0.099) showed a positive correlation with the prevalence of AD. Vegetable iron (p = 0.061 and p = 0.044, respectively), zinc (p = 0.022 and p = 0.007, respectively), vegetable protein (p = 0.074), and calcium (p = 0.057) had inhibitory effects on ADHD and its subtype. In conclusion, management of dietary and nutritional status should be considered to ameliorate ADHD and its subtypes in school-age children, and these relationships require further exploration in other settings.

Abstract Background Mediators, genomic and epigenomic characteristics involving in metabolism of arachidonic acid by cyclooxygenase (COX) and lipoxygenase (ALOX) and hepatic activation of clopidogrel have been individually suggested as factors associated with resistance against aspirin and clopidogrel. The present multi-center prospective cohort study evaluated whether the mediators, genomic and epigenomic characteristics participating in arachidonic acid metabolism and clopidogrel activation could be factors that improve the prediction of the aspirin and clopidogrel resistance in addition to cardiovascular risks. Methods We enrolled 988 patients with transient ischemic attack and ischemic stroke who were evaluated for a recurrence of ischemic stroke to confirm clinical resistance, and measured aspirin (ARU) and P2Y12 reaction units (PRU) using VerifyNow to assess laboratory resistance 12 weeks after aspirin and clopidogrel administration. We investigated whether mediators, genotypes, and promoter methylation of genes involved in COX and ALOX metabolisms and clopidogrel activation could synergistically improve the prediction of ischemic stroke recurrence and the ARU and PRU levels by integrating to the established cardiovascular risk factors. Results The logistic model to predict the recurrence used thromboxane A synthase 1 (TXAS1, rs41708) A/A genotype and ALOX12 promoter methylation as independent variables, and, improved sensitivity of recurrence prediction from 3.4% before to 13.8% after adding the mediators, genomic and epigenomic variables to the cardiovascular risks. The linear model we used to predict the ARU level included leukotriene B4, COX2 (rs20417) C/G and thromboxane A2 receptor (rs1131882) A/A genotypes with the addition of COX1 and ALOX15 promoter methylations as variables. The linear PRU prediction model included G/A and prostaglandin I receptor (rs4987262) G/A genotypes, COX2 and TXAS1 promoter methylation, as well as cytochrome P450 2C19*2 (rs4244285) A/A, G/A, and *3 (rs4986893) A/A genotypes as variables. The linear models for predicting ARU (r = 0.291, R2 = 0.033, p

Abstracts: In this study, mulberry leaf (ML) extract, along with ML processed by hot melt extrusion (HME) (HML), and ML processed by HME with biopolymer (HMLE), were utilized for the eco-friendly synthesis of silver nanoparticles (AgNPs). The physicochemical properties of AgNPs synthesized from ML, HML, and HMLE extracts were characterized using UV–Vis spectrophotometry, zeta potential analysis, transmission electron microscopy (TEM), dynamic light scattering (DLS), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). HME processing enhanced the active ingredients in the ML extract and increased the reduction efficiency of Ag ions. In the ABTS radical scavenging activity assay, AgNPs synthesized from HMLE (F3) exhibited the highest antioxidant activity with the lowest IC50 value. F3 also demonstrated the lowest minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Escherichia coli and Staphylococcus aureus. In the disk diffusion test, F3 showed the largest zone of inhibition, indicating the highest antimicrobial activity. In the anti-inflammatory assay using albumin inhibition, F3 achieved the highest inhibition rate, followed by the HMLE extract. In contrast, the extract group exhibited no activity in the antidiabetic test, while the AgNPs group showed the highest antidiabetic activity in F3. Additionally, F3 demonstrated the most potent anticancer activity against breast cancer cells, resulting in the lowest cell viability. Overall, this study suggests that AgNPs synthesized using ML extract enhanced via HME processing exhibit superior physiological activities compared to those synthesized using unprocessed ML extract.

Background/Aims: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is essential in diagnosing solid pancreatic lesions (SPLs), but without rapid on-site evaluation (ROSE), a repeat EUS-FNA/B is crucial for clarifying an inconclusive diagnosis. We aimed to evaluate factors associated with improved diagnostic performance of repeat EUS-FNA/B for initially inconclusive SPL diagnoses without ROSE. Methods: Of 5,894 patients subjected to EUS-FNA/B, 237 (4.0%) with an initially inconclusive diagnosis of SPLs were retrospectively enrolled from five tertiary medical centers between January 2016 and June 2021. Diagnostic performance and procedural factors of EUS-FNA/B were analyzed. Results: The diagnostic accuracies of first and repeat EUS-FNA/B were 96.2% and 67.6%, respectively. Of 237 patients with an inconclusive diagnosis from initial EUS-FNA/B, 150 were pathologically diagnosed after repeat EUS-FNA/B. In multivariate analysis of repeat EUS-FNA/B, tumor location (body/tail vs head: odds ratio [OR], 3.74; 95% confidence interval [CI], 1.48 to 9.46), number of needle passes (≥4 vs ≤3: OR, 4.80; 95% CI, 1.44 to 15.99), needle type (FNB vs FNA: OR, 3.26; 95% CI, 1.44 to 7.36), needle size (22 gauge vs 19/20 gauge: OR, 2.35; 95% CI, 1.19 to 4.62), and suction method (suction vs others: OR, 5.19; 95% CI, 1.30 to 20.75) were associated with a significantly improved diagnostic performance. Conclusions: Repeat EUS-FNA/B is essential for patients with an inconclusive EUS-FNA/B without ROSE. To improve the diagnostic performance of repeated EUS-FNA/B, it is recommended that 22-gauge FNB needles, ≥4 needle passes, and suction methods are used.

Synthesis of silver nanoparticles (AgNPs) using plant extracts has been proposed as a more advantageous and environmentally friendly alternative compared to existing physical/chemical methods. In this study, AgNPs were synthesized from silver nitrate using black mulberry (BM) extract. The biosynthesized AgNPs were characterized through an UV-visible spectrometer, X-ray diffraction, and transmission electron microscopy. Additionally, BM-AgNPs were subjected to antioxidant, antibacterial, anti-inflammatory, and anticancer activities. AgNPs biosynthesized from BM extract were dark brown in color and showed a strong peak at 437 nm, confirming that AgNPs were successfully synthesized. The size of AgNPs was 170.17 ± 12.65 nm, the polydispersity index was 0.281 ± 0.07, and the zeta potential value was −56.6 ± 0.56 mV, indicating that the particles were stable. The higher total phenol, flavonoid, and anthocyanin content of BM-AgNPs compared to BM extract indicates that the particles contain multiple active substances due to the formation of AgNPs. The DPPH and ABTS assays showed decreased IC50 values compared to BM extract, demonstrating improved antioxidant activity. AgNPs inhibited the growth of S. aureus and E. coli at 600 μg/mL, with minimum bactericidal concentrations determined to be 1000 and 1200 μg/mL, respectively. The anti-inflammatory activity was 64.28% at a BM-AgNPs concentration of 250 μg/mL. As the concentration increased, the difference from the standard decreased, indicating the inhibitory effect of AgNPs on bovine serum albumin denaturation. The viability of MCF-7 cells treated with BM-AgNPs was found to be significantly lower than that of cells treated with BM extract. The IC50 value of BM-AgNPs was determined to be 96.9 μg/mL. This study showed that BM-AgNPs have the potential to be used in the pharmaceutical industry as antioxidant, antibacterial, anti-inflammatory, and anticancer agents.

ABSTRACT Vancomycin and β-lactams are clinically important antibiotics that inhibit the formation of peptidoglycan cross-links, but their binding targets are different. The binding target of vancomycin is d-alanine-d-alanine (d-Ala-d-Ala), whereas that of β-lactam is penicillin-binding proteins (PBPs). In this study, we revealed the divergent effects of peptidoglycan (PG) carboxypeptidase DacA on vancomycin and β-lactam resistance in Escherichia coli and Bacillus subtilis. The deletion of DacA induced sensitivity to most β-lactams, whereas it induced strong resistance toward vancomycin. Notably, both phenotypes did not have a strong association with ld-transpeptidases, which are necessary for the formation of PG 3-3 cross-links and covalent bonds between PG and an Lpp outer membrane (OM) lipoprotein. Vancomycin resistance was induced by an increased amount of decoy d-Ala-d-Ala residues within PG, whereas β-lactam sensitivity was associated with physical interactions between DacA and PBPs. The presence of an OM permeability barrier strongly strengthened vancomycin resistance, but it significantly weakened β-lactam sensitivity. Collectively, our results revealed two distinct functions of DacA, which involved inverse modulation of bacterial resistance to clinically important antibiotics, β-lactams and vancomycin, and presented evidence for a link between DacA and PBPs. IMPORTANCE Bacterial PG hydrolases play important roles in various aspects of bacterial physiology, including cytokinesis, PG synthesis, quality control of PG, PG recycling, and stress adaptation. Of all the PG hydrolases, the role of PG carboxypeptidases is poorly understood, especially regarding their impacts on antibiotic resistance. We have revealed two distinct functions of PG carboxypeptidase DacA with respect to antibiotic resistance. The deletion of DacA led to sensitivity to most β-lactams, while it caused strong resistance to vancomycin. Our study provides novel insights into the roles of PG carboxypeptidases in the regulation of antibiotic resistance and a potential clue for the development of a drug to improve the clinical efficacy of β-lactam antibiotics.

Objective To investigate changes in blood glucose level after steroid injection in patients with type 2 diabetes mellitus (DM) and factors affecting those changes. Methods We retrospectively studied 51 patients with type 2 DM who underwent steroid injection for shoulder and back pain. Mean fasting blood sugar (FBS) levels for 7 days before steroid injection was used as the baseline blood glucose level, which was compared with FBS levels for 14 days after steroid injection. We compared the differences in blood glucose changes between HbA1c >7% and HbA1c ≤7% groups and those between insulin and non-insulin treated groups. Demographic data, injection site, and steroid dose were analyzed. Results Compared to baseline, blood glucose significantly (p=0.012) elevated 1 day after steroid injection but not 2 days after injection. In the HbA1c >7% and insulin groups, blood glucose was significantly increased 1 day after injection compared to that in the HbA1c ≤7% (p=0.011) and non-insulin (p=0.024) groups, respectively. Higher HbA1c level before injection was significantly (p=0.003) associated with the degree of blood glucose increase 1 day after injection. No significant differences were noted in the degree of blood glucose increase according to injection site or steroid dose. Conclusion Higher HbA1c level was associated with greater elevation in blood glucose 1 day after steroid injection. Careful monitoring of blood glucose is required on the first day after steroid injection in patients with poorly controlled DM.

Mulberry fruits are rich sources of anthocyanins that exhibit beneficial biological activity. These anthocyanins become instable in an aqueous media, leading to their low bioavailability. In this study, a colloidal dispersion was produced by processing mulberry samples with hot-melt extrusion. In this process, hydrophilic polymer matrices were used to disperse the compound in an aqueous media. Mulberry samples were processed with hot-melt extrusion and in the presence of an ionization agent and sodium alginate to form mulberry-extrudate solid formulations. The particle size of mulberry-extrudate solid formulations decreased, while the total phenol content, the total anthocyanin content, and solubility increased. Fourier transform infrared spectroscopy (FT-IR) revealed that mulberry-extrudate solid formulations now contained new functional groups, such as –COOH group. We investigated whether mulberry-extrudate solid formulations had a positive impact on the stability of anthocyanins. The non-extrudate mulberry sample and mulberry-extrudate solid formulations were incubated with a simulated gastric fluid system and an intestinal fluid system. The number of released anthocyanins was determined with HPLC. We found that anthocyanins were released rapidly from non-extrudate mulberry extract. Mulberry-extrudate solid formulations contained a large number of available anthocyanins even after being incubated for 180 min in the intestinal fluid system. Thus, hot-melt extrusion enhanced water solubility and stability of anthocyanins with the prolonged release.

Peat moss is an organic substance corroded by sphagnum moss and has a pH of 3.0–4.0. Elemental sulfur is sulfated and oxidized by the action of bacteria to become sulfuric acid. These biological factors can alter the soil environment. Blueberries require soil with a pH of 4.5–5.2 and high organic matter content. In this experiment, we investigated whether different treatment rates of peat moss, elemental sulfur, and sulfur-oxidizing bacteria affect changes in soil pH, physicochemical properties, and electrical conductivity. We detected strong changes in soil pH as a reaction to the supply of peat moss, elemental sulfur, and sulfur-oxidizing bacteria. The pH of the soil when peat moss and elemental sulfur each were supplied was reduced. In addition, the pH decreased faster when elemental sulfur and sulfur-oxidizing bacteria were supplied together than elemental sulfur alone, satisfying an acidic soil environment suitable for blueberry cultivation. In this experiment, it is shown that peat moss, elemental sulfur, and sulfur-oxidizing bacteria are suitable for lowering soil pH. It was demonstrated that when elemental sulfur and sulfur-oxidizing bacteria were treated together, the pH decreased faster than when treated with peat moss. It could be economically beneficial to farmers to use elemental sulfur and sulfur-oxidizing bacteria, which are cheaper than peat moss, to reduce the pH of the soil.

Monolayer and multilayer molybdenum disulfide (MoS2) materials are semiconductors with direct/indirect bandgaps of 1.2–1.8 eV and are attractive due to their changes in response to electrical, physicochemical, biological, and mechanical factors. Since the desired electrical properties of MoS2 are known, research on its electrical properties has increased, with focus on the deposition and growth of large-area MoS2 and its functionalization. While research on the large-scale production of MoS2 is actively underway, there is a lack of studies on functionalization approaches, which are essential since functional groups can help to dissolve particles or provide adequate reactivity. Strategies for producing films of functionalized MoS2 are rare, and what methods do exist are either complex or inefficient. This work introduces an efficient way to functionalize MoS2. Functional groups are formed on the surface by exposing MoS2 with surface sulfur vacancies generated by plasma treatment to 3-mercaptopropionic acid. This technique can create 1.8 times as many carboxyl groups on the MoS2 surface compared with previously reported strategies. The MoS2-based gas sensor fabricated using the proposed method shows a 2.6 times higher sensitivity and much lower detection limit than the untreated device.

The ferric uptake regulator (Fur) family proteins include sensors of Fe (Fur), Zn (Zur), and peroxide (PerR). Among Fur family proteins, Fur and Zur are ubiquitous in most prokaryotic organisms, whereas PerR exists mainly in Gram positive bacteria as a functional homologue of OxyR. Gram positive bacteria such as Bacillus subtilis, Listeria monocytogenes and Staphylococcus aureus encode three Fur family proteins: Fur, Zur, and PerR. In this study, we identified five Fur family proteins from B. licheniformis: two novel PerR-like proteins (BL00690 and BL00950) in addition to Fur (BL05249), Zur (BL03703), and PerR (BL00075) homologues. Our data indicate that all of the five B. licheniformis Fur homologues contain a structural Zn2+ site composed of four cysteine residues like many other Fur family proteins. Furthermore, we provide evidence that the PerR-like proteins (BL00690 and BL00950) as well as PerRBL (BL00075), but not FurBL (BL05249) and ZurBL (BL03703), can sense H2O2 by histidine oxidation with different sensitivity. We also show that PerR2 (BL00690) has a PerR-like repressor activity for PerR-regulated genes in vivo. Taken together, our results suggest that B. licheniformis contains three PerR subfamily proteins which can sense H2O2 by histidine oxidation not by cysteine oxidation, in addition to Fur and Zur.

Compound K, a major metabolite of ginsenosides Rb1, which is produced by human intestinal bacteria after oral administration, is one of the main pharmacologic compounds found in ginseng. In our previous study, we demonstrated that compound K inhibited the production of nitric oxide (NO) and prostaglandin E2 in lipopolysaccharide (LPS)-treated RAW264.7 cells. However, the mechanisms by which compound K may be effective against inflammation remain unknown. In the present study, compound K significantly inhibited LPS-induced NO production by suppression of inducible NO synthase (iNOS) in LPS-treated RAW264.7 cells. Compound K also inhibited LPS-induced cyclooxygenase-2 (COX-2) expression at both the mRNA and protein levels. It effectively suppressed both the release and mRNA expression levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and IL-6. The anti-inflammatory effects of compound K appeared to occur via inhibition of LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs) and inhibition of NF-κB translocation from the cytosol to the nucleus by suppressing phosphorylation of inhibitory kappa B-α (IκB-α). Furthermore, we showed that compound K inhibited LPS-induced NO generation in an experimental zebrafish model. Considering these results, compound K could potentially be developed as a natural anti-inflammatory agent.

Gelidium elegans extract (GEE) is derived from a red alga from the Asia–Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted 5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.