Mechanism of RNA m6 A methylation modification regulating NLRP3 inflammasome activation for hand, foot, and mouth disease progression.

Some children infected with hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) progressed to severe disease with various neurological complications in the short term, with a poor prognosis and high mortality. Studies had revealed that RNA N6 -methyladenosine (m6 A) modification had a significant impact on EV71 replication, but it was unknown how m6 A modification regulated the host cell's innate immune response brought on by EV71 infection. We used MeRIP-seq (methylation RNA immunoprecipitation sequencing), RNA-seq (RNA sequencing), cell transfection, and other techniques. MeRIP-seq and RNA-seq results showed the m6 A methylation modification map of control and EV71-infected groups of RD cells. And multilevel validation indicated that decreased expression of demethylase FTO (fat mass and obesity-associated protein) was responsible for the elevated total m6 A modification levels in EV71-infected RD cells and that thioredoxin interacting protein (TXNIP) may be a target gene for demethylase FTO action. Further functional experiments showed that demethylase knockdown of FTO promoted TXNIP expression, activation of NLRP3 inflammasome and promoted the release of proinflammatory factors in vitro, and the opposite result occurred with demethylase FTO overexpression. And further tested in an animal model of EV71 infection in vitro, with results consistent with in vitro. Our findings elucidated that depletion of the demethylase FTO during EV71 infection increased the m6 A modification level of TXNIP mRNA 3' untranslated region (UTR), enhancing mRNA stability, and promoting TXNIP expression. Consequently, the NLRP3 inflammasome was stimulated, leading to the release of proinflammatory factors and facilitating HFMD progression.

Risk of adverse outcomes in inflammatory bowel disease patients infected with SARS-CoV-2: a systematic review and meta-analysis.

BACKGROUND: Between people with and without inflammatory bowel disease (IBD), there was no statistically significant difference in the probability of contracting the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the risk of adverse outcomes in IBD patients after virus infection remains unclear. METHODS: Eligible studies conducted from January 1, 2020 to March 17, 2022 were obtained by searching PubMed, Embase, and Web of Science. Information was collected in tables from the included studies. Random-effects and fixed-effects models were used as measures for the pooled estimates. All data were estimated by R version 4.1.3. RESULTS: Twenty-four studies were included. The risk ratio (RR) of adverse outcomes in COVID-19 patients with IBD increased by 32% (RR 1.32; 95% CI 1.06-1.66) relative to COVID-19 patients without IBD. The RR of mortality was higher in COVID-19 patients with IBD from Europe (RR 1.72; 95% CI 1.11-2.67) than in those that were not from Europe (RR 1.00; 95% CI 0.79-1.26; χ2 = 4.67; P = 0.03). Patients with ulcerative colitis were at higher risk of adverse outcomes after SARS-CoV-2 infection than patients with Crohn's disease patients (RR1.38; 95% CI 1.27-1.50). The IBD drugs treatment was associated with the risk of adverse outcomes, the pooled odds ratio (OR) of mesalazine (1.79; 95% CI 1.59-2.02), immunomodulators (1.30; 95% CI 1.10-1.53), and anti-TNF (0.47; 95% CI 0.41-0.53) were assessed. CONCLUSION: COVID-19 patients with IBD had an increased risk of adverse outcomes than those without IBD, whereas anti-TNF treatment might reduce the risk.

Groundwater antibiotics and microplastics in a drinking-water source area, northern China: Occurrence, spatial distribution, risk assessment, and correlation.

In recent years, antibiotics and microplastics have both received increasing attention. However, the contamination and correlation between the two pollutants in the groundwater of drinking-water source areas has not yet been considered. In this study, eight antibiotics were detected in 81 groundwater samples from a drinking-water source area. These were trimethoprim (TMP), sulfadimidine (SDD), sulfadiazine (SDZ), sulfamethoxazole (SMX), sulfachloropyridazine (SCP), norfloxacin (NOR), ciprofloxacin (CIP) and enrofloxacin (ENRO). Detection rates ranged from 1.23% to 95.06% and the maximum concentration ranged from 0.44 ng/L to 45.40 ng/L. Antibiotics in the groundwater pose no threat to human health, while only ENRO, CIP, NOR, SMX, and SDZ posed medium to low risks to the aquatic ecosystem. In contrast, the detection rate of microplastics was 100% with abundance values ranging from 4 n/L to 72 n/L, with an average of 29 n/L. Microplastic polymers were identified as polyamide, polyethylene, polypropylene, polyvinyl chloride and polystyrene. These also occurred in surface water but the particle sizes in groundwater were lower than those in the surface water. Through correlation analysis, it was found that NOR, ENRO and total antibiotic concentrations were significantly correlated with microplastic abundances. This study revealed the contamination and potential risks of antibiotics and microplastics in the groundwater of a drinking-water source area and found a correlation between them, indicating that risk management of antibiotics and microplastics in groundwater should be highly concerned.

N6-methyladenosine modification of hypoxia-inducible factor-1α regulates Helicobacter pylori-associated gastric cancer via the PI3K/AKT pathway.

BACKGROUND: Helicobacter pylori (H. pylori) colonizes the human gastric mucosa and is implicated in the development of gastric cancer (GC). The tumor microenvironment is characterized by hypoxia, where hypoxia-inducible factor-1α (HIF-1α) plays a key role as a transcription factor, but the mechanisms underlying H. pylori-induced HIF-1α expression and carcinogenesis remain unclear. AIM: To explore the underlying mechanism of H. pylori-induced HIF-1α expression in promoting the malignant biological behavior of gastric epithelial cells (GES-1). METHODS: The study was conducted with human GES-1 cells in vitro. Relative protein levels of methyltransferase-like protein 14 (METTL14), HIF-1α, main proteins of the PI3K/AKT pathway, epithelial-mesenchymal transition (EMT) biomarkers, and invasion indicators were detected by Western blot. Relative mRNA levels of METTL14 and HIF-1α were detected by quantitative reverse transcription-polymerase chain reaction. mRNA stability was evaluated using actinomycin D, and the interaction between METTL14 and HIF-1α was confirmed by immunofluorescence staining. Cell proliferation and migration were evaluated by cell counting kit-8 assay and wound healing assay, respectively. RESULTS: H. pylori promoted HIF-1α expression and activated the PI3K/AKT pathway. Notably, METTL14 was downregulated in H. pylori-infected gastric mucosal epithelial cells and positively regulated HIF-1α expression. Functional experiments showed that the overexpression of HIF-1α or knockdown of METTL14 enhanced the activity of the PI3K/AKT pathway, thereby driving a series of malignant transformation, such as EMT and cell proliferation, migration, and invasion. By contrast, the knockdown of HIF-1α or overexpression of METTL14 had an opposite effect. CONCLUSION: H. pylori-induced underexpression of METTL14 promotes the translation of HIF-1α and accelerates tumor progression by activating the PI3K/AKT pathway. These results provide novel insights into the carcinogenesis of GC.

EMMTE: An Excel VBA tool for source apportionment of nitrate based on the stable isotope mixing model.

Dual nitrate stable isotopes combined with end-member mixing models are typically used to identify nitrate sources in fields of geochemistry and environmental science, which helps to quantitively depict the geochemical behaviors of nitrate and accurately control the sources of nitrate pollution in waters. Recently, various models with different computation principles, working efficiency, and operation difficulty have been developed and applied in the source apportionment of nitrate. In this paper, an end-member mixing model tool on Excel™, namely EMMTE, has been written with Visual Basic for Application (VBA) and built into a macro-enabled Excel™ spreadsheet. Monte Carlo simulation and constraint relative deviation between the observed and the predicted values were included in the working algorithm to solve the mass balance equation. After comparison with the internationally recognized Bayesian framework (mixing stable isotope analysis in R, MixSIAR) in different cases (three practical cases and one virtual case), the preliminary results showed that the contribution of various sources to groundwater nitrate calculated by EMMTE was highly consistent with that by MixSIAR and the performance of EMMTE seemed to be as good as that of MixSIAR as indicated by the higher goodness-of-prediction, lower root-mean-square error, and lower relative deviation. Therefore, EMMTE is applicable in the source apportionment of groundwater nitrate, and might also be extended to other water bodies and mixtures. It provides a simple, feasible, and user-friendly for front-line workers without experience with MixSIAR to quantitively source apportionment of nitrate in waters.

Novel insights into source apportionment of dissolved organic matter in aquifer affected by anthropogenic groundwater recharge: Applicability of end-member mixing analysis based optical indices.

The composition and main sources of dissolved organic matter (DOM) in groundwater may change significantly under long-term anthropogenic groundwater recharge (AGR); however, the impact of AGR on quantitative sources of groundwater DOM has seldom been reported. This study evaluated the applicability of optical indices combined with mixing stable isotope analysis in R (MixSIAR) in end-member mixing analysis (EMMA) of groundwater DOM. Fluorescent indices, including C1%, C2%, and C3%, were more sensitive to AGR than other absorbance indices, as indicated by the significant difference between the dominant area of artificial groundwater recharged by surface water and the dominant area of natural groundwater recharged by atmospheric precipitation (NGRP). BIX-C1% was selected as the optimal dual index after the screening protocol of groundwater DOM for EMMA. Our results showed that DOM in the aquifer was mainly subject to autochthonous DOM and the contribution of background groundwater to AGRSW and NGRP groundwater accounted for 36.15% ± 32.41% and 55.46% ± 37.17% (p < 0.05), respectively. Therefore, AGR significantly changed the native DOM in the groundwater. In allochthonous sources of DOM, sewage and surface water contributed 29.54% ± 24.87% and 21.32% ± 28.08%, and 24.79% ± 15.56% and 15.21% ± 14.20% to AGRSW and NGRP groundwater, respectively. The contribution of surface water to AGRSW groundwater was significantly higher than that to NGRP groundwater (p < 0.05), indicating that AGR introduced significantly more DOM from surface water to groundwater. This study provides novel insights into the quantitative source apportionment of DOM in groundwater under long-term AGR, which will facilitate the environmental risk assessment of present AGR measures and the sustainable management of clean water.

Impacts of anthropogenic groundwater recharge (AGR) on nitrate dynamics in a phreatic aquifer revealed by hydrochemical and isotopic technologies.

Although anthropogenic groundwater recharge (AGR) can either elevate or decline the concentration of nitrate in the phreatic aquifer with high hydraulic conductivity, the long-term impact of AGR on nitrate dynamics in the phreatic aquifer and its reason is seldom disclosed. In this study, the hydrogen and oxygen stable isotopes (δ2H-H2O and δ18O-H2O) combined with mixing stable isotope analysis in R (MixSIAR) were used to group the study area into the dominant area of AGR by surface water (AGRSW) and the dominant area of natural groundwater recharged by precipitation (NGRP). Hydrochemical parameters and multiple stable isotopes, including δ2H-H2O, δ18O-H2O, δ15N-NO3-, δ18O-NO3-, and δ13C-DIC, were applied to explore the impacts of AGR on the concentration, biogeochemical processes, and main sources of nitrate. The results showed that AGR by surface water with low nitrate content can reduce nitrate pollution in groundwater. The characteristic of δ18O-NO3- value revealed that nitrification was the primary biogeochemical process of nitrogen in groundwater. AGR may enhance nitrification as indicated by the δ18O-NO3- value closer to the nitrification theoretical line. Dual nitrate stable isotopes and MixSIAR revealed that chemical fertilizer (CF), soil nitrogen (SN), and surface water (SW) contributed 10.88%, 49.92%, and 27.64% to nitrate in AGRSW groundwater, respectively, which was significantly different from their contributions to NGRP groundwater (p < 0.05). Notably, AGR significantly increased the contribution of SW but decreased the contribution of CF and SN in groundwater. This study provided a basis and guidance for groundwater quality assessment and pollution control in the phreatic aquifer with high hydraulic conductivity.

Physical fitness and associated factors among primary and middle school students in Henan Province in 2019 / 中国学校卫生

Objective@#To understand physical fitness among primary and middle school students in Henan Province, so as to provide theoretical basis for physical fitness promotion among primary and middle school students.@*Methods@#Based on data of National Survey on Student Physical Fitness and Health in Henan Province in 2019, a total of 42 734 students were investigated. The Z value of each physical fitness index were calculated by Z method, physical fitness index (PFI) was obtained to reflect the physical fitness condition synthetically. Physical fitness of different groups were compared, and associated factors of PFI were analyzed by multiple linear regression.@*Results@#Lung capacity, grip strength, standing long jump, 50 m run, 50 m×8 shuttle run and PFI in boys were [(2 552.1±1 226.5)mL, (26.0±13.9)N, (171.0±43.7)cm, (9.3±1.8)s, (132.1±22.6)s, (1.4±3.6)], respectively, which were significantly higher than that of girls [(1 965.2±765.3)mL, (19.1±8.2)N, (142.4±26.6)cm, (10.5±1.4)s, (136.9±21.1)s, (-1.4±3.2)]( t =59.35,62.66,81.87,-74.92,-16.72,85.96, P <0.01). The seated forward flexion of boys [(7.0±7.5)cm] was significantly lower than that of girls[(11.8±7.1)cm], the difference was statistically significant ( t =-68.57， P <0.01). Significant sex differences were observed in physical fitness at different age ( P <0.01). There was a certain gap between urban boys and rural boys in terms of strength quality, endurance quality and flexibility quality, and the physical quality of urban girls was better than that of rural girls as a whole. The detection rates of poor eyesight, malnutrition, overweight and obesity, anemia and high blood pressure of primary and middle school students were 68.0%, 5.4%, 26.0%, 15.9% and 18.0%, respectively. Region, sex, age and nutritional status(malnutrition,overweight and obesity) were the influencing factors of PFI( β =-0.23,-2.92,-0.11,-1.19, -0.78 , P <0.05).@*Conclusion@#Physical fitness among primary and middle school students varies in gender, age group, region and disease condition in Henan Province. Scientific intervention should be administered, especially for rural, female students, senior students, undernourished and overweight and obese students, to improve health awareness and physical fitness.