Circulating miRNAs associate with historical childhood asthma hospitalization in different serum vitamin D groups.

BACKGROUND: Vitamin D may help to alleviate asthma exacerbation because of its anti-inflammation effect, but the evidence is inconsistent in childhood asthma. MiRNAs are important mediators in asthma pathogenesis and also excellent non-invasive biomarkers. We hypothesized that circulating miRNAs are associated with asthma exacerbation and modified by vitamin D levels. METHODS: We sequenced baseline serum miRNAs from 461 participants in the Childhood Asthma Management Program (CAMP). Logistic regression was used to associate miRNA expression with asthma exacerbation through interaction analysis first and then stratified by vitamin D insufficient and sufficient groups. Microarray from lymphoblastoid B-cells (LCLs) treated by vitamin D or sham of 43 subjects in CAMP were used for validation in vitro. The function of miRNAs was associated with gene modules by weighted gene co-expression network analysis (WGCNA). RESULTS: We identified eleven miRNAs associated with asthma exacerbation with vitamin D effect modification. Of which, five were significant in vitamin D insufficient group and nine were significant in vitamin D sufficient group. Six miRNAs, including hsa-miR-143-3p, hsa-miR-192-5p, hsa-miR-151a-5p, hsa-miR-24-3p, hsa-miR-22-3p and hsa-miR-451a were significantly associated with gene modules of immune-related functions, implying miRNAs may mediate vitamin D effect on asthma exacerbation through immune pathways. In addition, hsa-miR-143-3p and hsa-miR-451a are potential predictors of childhood asthma exacerbation at different vitamin D levels. CONCLUSIONS: miRNAs are potential mediators of asthma exacerbation and their effects are directly impacted by vitamin D levels.

A novel piwi-interacting RNA associates with type 2-high asthma phenotypes.

BACKGROUND: Piwi-interacting RNAs (piRNAs), comprising the largest noncoding RNA group, regulate transcriptional processes. Whether piRNAs are associated with type 2 (T2)-high asthma is unknown. OBJECTIVE: We sought to investigate the association between piRNAs and T2-high asthma in childhood asthma. METHODS: We sequenced plasma samples from 462 subjects in the Childhood Asthma Management Program (CAMP) as the discovery cohort and 1165 subjects in the Genetics of Asthma in Costa Rica Study (GACRS) as a replication cohort. Sequencing reads were filtered first, and piRNA reads were annotated and normalized. Linear regression was used for the association analysis of piRNAs and peripheral blood eosinophil count, total serum IgE level, and long-term asthma exacerbation in children with asthma. Mediation analysis was performed to investigate the effect direction. We then ascertained if the circulating piRNAs were present in asthmatic airway epithelial cells in a Gene Expression Omnibus (GEO; www.ncbi.nlm.nih.gov/geo) public data set. RESULTS: Fifteen piRNAs were significantly associated with eosinophil count in CAMP (P ≤ .05), and 3 were successfully replicated in GACRS. Eleven piRNAs were associated with total IgE in CAMP, and one of these was replicated in GACRS. All 22 significant piRNAs were identified in epithelial cells in vitro, and 6 of these were differentially expressed between subjects with asthma and healthy controls. Fourteen piRNAs were associated with long-term asthma exacerbation, and effect of piRNAs on long-term asthma exacerbation are mediated through eosinophil count and serum IgE level. CONCLUSION: piRNAs are associated with peripheral blood eosinophils and total serum IgE in childhood asthma and may play important roles in T2-high asthma.

Removal of sulfonamide antibiotics by a sonocatalytic Fenton-like reaction: Efficiency and mechanisms.

With the widespread use of sulfonamide antibiotics (SAs), SAs are detected as residues in aquatic environments, posing a serious threat to human life and safety. Because of their high water solubility, fast transmission rate, and strong antibacterial properties, the safe disposal of SAs has become a key constraint for water quality assurance. Therefore, an ultrasound (US)-assisted zero-valent iron (ZVI)/persulfate (PS) system was proposed to explore the rapid and effective degradation of SAs. Comparative experiments were performed to study the removal of sulfadiazine (SDZ) by US, ZVI, PS, US/ZVI, US/PS, ZVI/PS, and US-ZVI/PS systems, respectively. Experimental results indicated that the highest removal efficiency of SDZ was ahieved in US-ZVI/PS system (97.4%), which were 2-44 times higher than that in other systems. Furthermore, the degradation efficiency of five typical SAs was achieved over 95%, demonstrating the effectiveness of the US ZVI/PS system for SAs removal. Also, quantum chemical computations for potential reactive sites of SAs and intermediate product detection by HPLC‒MS/MS were performed. The radical attack on active sites of SAs, such as N atom (number 7), was the main reason for SAs removal in US-ZVI/PS system. Besides, the common degradation pathways of six typical SAs were defined as S-N bond cleavage, C-N bond cleavage, benzene ring hydroxylation, aniline oxidation, and R substituent oxidation. Interestingly, the unique pathway of "SO2 group extraction" was observed in the degradation of six-membered ring SAs. Therefore, the US-ZVI/PS system is a promising and cost-effective method for the removal of SAs and other refractory pollutants.

Application of the biogas residue of anaerobic co-digestion of gentamicin mycelial residues and wheat straw as soil amendment: Focus on nutrients supply, soil enzyme activities and antibiotic resistance genes.

Land utilization of the biogas residue (BR) produced by anaerobic co-digestion of gentamicin mycelial residues (GMRs) and wheat straw is a promising method to achieve the deep recycling of GMRs. This study evaluated the feasibility and efficacy of application of using BR as a soil amendment by using a pot experiment. Results indicated that BR could improve the soil fertility better than commercial chicken manure fertilizer (CMF) in terms of the soil enzyme activities and nutrients supply. Random Forest (RF) model was applied to predict soil enzyme activities and identify key influencing factors. Combining the Random Forest (RF) model with the Three-dimensional Excitation-emission Matrix and Parallel Factor (3D-EEM-PARAFAC) analysis, revealing that humic-like substances provided by BR protected soil enzymes, thus improving soil fertility. Furthermore, gentamicin and antibiotic resistance genes (ARGs)/mobile genetic elements (MEGs) introduced by BR decreased greatly after cultivation, implying a low risk of antimicrobial resistance. This study suggested that reasonable application of BR could improve soil nutrients supply, soil enzyme activity and control antimicrobial resistance risk.

Base-catalyzed hydrolysis of spectinomycin in aqueous solutions: Kinetics and mechanisms.

Hydrolysis plays an imperative role in the abiotic transformation process of antibiotics in aqueous solutions. However, little information is available on the hydrolysis process of spectinomycin (an aminocyclitol antibiotic). This study systematically investigated the spectinomycin hydrolysis kinetics and mechanisms under different pH via experiments and density functional theory (DFT) computation. Hydrolysis was first conducted in a pure water system under pH of 4.0-9.0 and temperature of 25 °C, 50 °C and 70 °C, respectively. Results showed that hydrolysis was highly dependent on pH and temperature. When pH > 6.0, spectinomycin hydrolysis was accelerated by the catalysis of OH-. Meanwhile, the hydrolysis rate increased with the elevation of temperature. Then, for the reference of the practical environment, the general base-catalyzed hydrolysis and mechanisms were studied under environmental pH 6.0-8.0 and 25 °C. DFT calculation demonstrated that base-catalyzed hydrolysis of spectinomycin could be more thermodynamically and kinetically favorable based on the lower Gibbs free energies of reaction and Gibbs free energies of activation. Further, instead of specific base catalysis (OH-), the general base catalysis (e.g., phosphate buffer) was also found to promote hydrolysis efficiency. The antibacterial activity and ecotoxicities of the hydrolysis product were analyzed to be lower than the precursor, thereby decreasing the environmental impact of spectinomycin.

The Effect of Operating Strategies on the Anaerobic Digestion of Gentamicin Mycelial Residues: Insights into the Enhancement of Methane Production and Attenuation of Gentamicin Resistance.

Anaerobic digestion (AD) has been widely employed for converting various biowastes into renewable energy. However, AD of gentamicin mycelial residues (GMRs, a byproduct of gentamicin production) is limited by ammonia inhibition and antimicrobial resistance risk. Compared to mesophilic AD (MMAD) of GMRs, this study looked into three semicontinuous AD processes, i.e., codigestion with wheat straw, thermophilic digestion (TAcoD), and AD at shortened retention time (RT). Results showed that a stable and safe AD could be achieved under suitable operating conditions. Co-digestion could effectively mitigate the adverse effect of ammonia inhibition. The methane production increased by 35.86% in TAcoD compared to that in MMAD and 43.99% of hazardous waste was reduced in TAcoD. Concerning the antimicrobial resistance of AD system, gentamicin was degraded efficiently and the degradation process was not involved in the expression of antibiotic resistance genes (ARGs) related to modifying enzyme. Effective removal of ARGs under three operating strategies was associated with a higher reduction in bacterial abundance of potential hosts. In addition, the changes in the relevant proteins for transformation and conjugation as predicted by PICRUSt suggested that thermophilic condition and shorter RT were conducive to the reduction of the dissemination risks of ARGs.

Responses of methane production, microbial community and antibiotic resistance genes to the mixing ratio of gentamicin mycelial residues and wheat straw in anaerobic co-digestion process.

Anaerobic co-digestion (AcoD) of gentamicin mycelial residues (GMRs), a kind of nitrogen-rich biowaste, and wheat straw (WS) is an attractive technology for the recycling of GMRs. However, the effects of the co-substrate ratio on methane production, system stability and antimicrobial resistance during co-digestion remain unclear. Thus, this study aimed to fill in the blanks through AcoD of GMRs and WS with different mixing ratios (1:0, 2:1, 1:1, 1:2, 0:1, VS basis) via batch tests. Results showed that AcoD facilitated methane production than mono anaerobic digestion and reduced the accumulation of the toxic substances, such as ammonia nitrogen and humic-like substances. The maximum methane production was obtained at the reactors with the mixing ratio of 1:1 and 1:2 (R-1:1 and R-1:2), which matched with the relative abundance of key enzymes related to methanogenesis predicted by PICRUSt. Microbial community analysis indicated that Methanosaeta was the most dominant methanogen in the AcoD reactors. The highest relative abundance of Methanosaeta (45.1%) was obtained at R-1:1 due to the appropriate AcoD conditions, thus, providing greater possibilities for high stability of AcoD system. Additionally, AcoD of the GMRs and WS under the mixing ratio of 1:1 and 1:2 did not prompt the increase of antibiotic resistance genes (ARGs). Not only that, the likelihood of horizontal gene transfer declined in R-1:1 due to the weaker connection and transport between host and recipient bacteria. Findings of this study suggested that the suitable mixing ratio of GMRs and WS contributes to methane production and system stability, and reduces the dissemination risks of ARGs.

Alkaline-thermal pretreatment of spectinomycin mycelial residues: Insights on anaerobic biodegradability and the fate of antibiotic resistance genes.

Alkaline-thermal (AT) pretreatment is an economical and efficient pretreatment method to improve anaerobic biodegradability of biowaste. This study investigated the effect of AT pretreatment of spectinomycin mycelial residues (SMRs) for promoting anaerobic biodegradability along with the reduction of antibiotic resistance genes (ARGs), and thus obtained the optimal conditions of AT pretreatment. Biomethane potential (BMP) test was conducted to evaluate the anaerobic biodegradability of untreated and pretreated SMRs, and the fate of ARGs was tracked by quantitative polymerase chain reaction. Results showed that the modified Gompertz model fitted the results of BMP tests satisfactorily. Furthermore, AT pretreatment promoted BMP (B0) and reduced lag phase (λ) effectively. These were attributed to the solubilization of SMRs. The analyses of the changes in dissolved organic matter indicated that AT pretreatment could facilitate the solubilization of both biodegradable (e.g. protein) and recalcitrant matter (e.g. humic-like, analyzing by EEMs-PARAFAC), which had a significant corresponding positive (Person correlation, p < 0.01) and negative (Partial correlation, p < 0.01) influences on anaerobic biodegradability. However, the positive effects surpassed the negative effects, promoting the overall anaerobic biodegradability of SMRs. In addition, a considerable reduction of ARGs (by 0.62-1.36 log units) was observed at pH ≥ 12, attributed to the hydrolysis of phosphodiester bond of DNA in strong alkaline solution. Considering both anaerobic biodegradability and ARGs, the optimal AT condition was concluded as pH 12, temperature 90 °C and time 120 min.

Anaerobic digestion of spectinomycin mycelial residues pretreated by thermal hydrolysis: removal of spectinomycin and enhancement of biogas production.

Anaerobic digestion (AD) is an effective technology to dispose antibiotic mycelial residues, but biogas production is influenced by hydrolysis rates and antibiotic residue. Herein, the effects of thermal hydrolysis pretreatment for AD of spectinomycin mycelial residues (SMRs) were investigated. The results showed that the removal ratio of spectinomycin was increased while the temperature of pretreatment was escalating. Meanwhile, thermal hydrolysis facilitated the dissolution of organic matters. However, non-biodegradable substances measured by fluorescence excitation-emission matrix accumulated and thus had an adverse influence on biogas production. Based on batch assays, the optimal pretreatment temperature for SMRs was 120 °C. The removal of spectinomycin was benefit for biogas production (increasing by 7.6%), and the overall biogas production increased by 27.6% compared with 289.90 mL gVS-1 of untreated SMRs. The microbial community analysis revealed that spectinomycin (265 mg L-1) might influence bacteria in the early stage of AD (first 5 days), while redundancy analysis showed that spectinomycin had a non-significant influence on community succession over the 32 days of fermentation.