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The rapid emergence of SARS-CoV-2 variants of concern, the complexity of infection, and the functional redundancy of host factors, underscore an urgent need for broad-spectrum antivirals against the continuous COVID-19 pandemic, with drug repurposing as a viable therapeutic strategy. Here we report the potential of RNA G-quadruplex (RG4)-targeting therapeutic strategy for SARS-CoV-2 entry. Combining bioinformatics, biochemical and biophysical approaches, we characterize the existence of RG4s in several SARS-CoV-2 host factors. In silico screening followed by experimental validation identify Topotecan (TPT) and Berbamine (BBM), two clinical approved drugs, as RG4-stabilizing agents with repurposing potential for COVID-19. Both TPT and BBM can reduce the protein level of RG4-containing host factors, including ACE2, AXL, FURIN, and TMPRSS2. Intriguingly, TPT and BBM block SARS-CoV-2 pseudovirus entry into target cells in vitro and murine tissues in vivo. These findings emphasize the significance of RG4 in SARS-CoV-2 pathogenesis and provide a potential broad-spectrum antiviral strategy for COVID-19 prevention and treatment.
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COVID-19 , SARS-CoV-2 , Humanos , Animais , Camundongos , SARS-CoV-2/metabolismo , RNA , Pandemias , Antivirais/metabolismo , Internalização do Vírus , Glicoproteína da Espícula de CoronavírusRESUMO
RATIONALE: The development of analytical screening techniques for pesticides is crucial for preventing and mitigating environmental contamination. Mass spectrometry-based screening methods differ based on the complexity of the sample matrix and the diversity of the target compounds. One of the major challenges is balancing cost reduction in the extraction process with the optimization of analytical results. This protocol introduces a universal and efficient scheme for the qualitative and quantitative schemes for 45 pesticides within a single analytical run. METHODS: Water samples were extracted using an SPE column, with the pH adjusted to 7. Soil samples were processed using a modified QuEChERS method. The pretreatment for water samples emphasized selecting appropriate SPE columns and optimizing pH, while for soil samples, the focus was on choosing suitable extraction solvents and extraction salt packages. The enriched samples were then analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was evaluated for accuracy, precision, detection limits, and matrix effects. RESULTS: The method enabled the simultaneous detection of 45 pesticides within a 15-minute analysis period. SPE recoveries ranged from 56.1% to 118.8%. Instrumental detection limits varied between 0.02 and 1 pg, while method detection limits extended from 0.05 to 18.47 ng/l in soil and water matrices. The approach was successfully applied to water and soil samples, with the pesticide concentration ranging from 0.1 ng/L to 38 µg/L. CONCLUSIONS: The protocol substantially enhances the characterization and quantification of 45 pesticides in environmental samples, achieving a remarkable reduction in detection limits by an order of magnitude compared to previous research. This method enables the simultaneous detection of pesticides in both water and soil matrices using a single system, addressing the challenges of using separate systems for different environmental media. Furthermore, this protocol provides a crucial theoretical foundation for managing and safeguarding against pesticide pollution.
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Coastal wetlands contribute to the mitigation of climate change through the sequestration of "blue carbon". Microbial necromass, lignin, and glycoproteins (i.e., glomalin-related soil proteins (GRSP)), as important components of soil organic carbon (SOC), are sensitive to environmental change. However, their contributions to blue carbon formation and the underlying factors remain largely unresolved. To address this paucity of knowledge, we investigated their contributions to blue carbon formation along a salinity gradient in coastal marshes. Our results revealed decreasing contributions of microbial necromass and lignin to blue carbon as the salinity increased, while GRSP showed an opposite trend. Using random forest models, we showed that their contributions to SOC were dependent on microbial biomass and resource stoichiometry. In N-limited saline soils, contributions of microbial necromass to SOC decreased due to increased N-acquisition enzyme activity. Decreases in lignin contributions were linked to reduced mineral protection offered by short-range-ordered Fe (FeSRO). Partial least-squares path modeling (PLS-PM) further indicated that GRSP could increase microbial necromass and lignin formation by enhancing mineral protection. Our findings have implications for improving the accumulation of refractory and mineral-bound organic matter in coastal wetlands, considering the current scenario of heightened nutrient discharge and sea-level rise.
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Carbono , Solo , Lignina , Glicoproteínas , Proteínas Fúngicas , MineraisRESUMO
Fine particulate matter (PM2.5) is a risk factor of cardiovascular disease. Associations between PM2.5 compositions and cardiovascular disease are a point of special interest but inconsistent. This study aimed to explore the cardiovascular effects of heavy metal(loid) compositions in PM2.5. Data for mortality, air pollutants and meteorological factors in Anyang, China from 2017 to 2021 were collected. Heavy metal(loid) in PM2.5 were monitored and examined monthly. A Case-crossover design was applied to the estimated data set. The interquartile range increase in cadmium (Cd), antimony (Sb) and arsenic (As) at lag 1 was associated with increment of 8.1% (95% CI: 3.3, 13.2), 4.8% (95% CI: 0.2, 9.5) and 3.5% (95% CI: 1.1, 6.0) cardiovascular mortality. Selenium in lag 2 was inversely associated with cerebrovascular mortality (RR = 0.920 95% CI: 0.862, 0.983). Current-day exposure of aluminum was positively associated with mortality from ischemic heart disease (RR = 1.083 95% CI: 1.001, 1.172). Stratified analysis indicated sex, age and season modified the cardiovascular effects of As (P < 0.05). Our study reveals that heavy metal(loid) play key roles in adverse effects of PM2.5. Cd, Sb and As were significant risk factors of cardiovascular mortality. These findings have potential implications for accurate air pollutants control and management to improve public health benefits.
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Poluentes Atmosféricos , Doenças Cardiovasculares , Metais Pesados , Material Particulado , Material Particulado/análise , Material Particulado/efeitos adversos , Humanos , China/epidemiologia , Metais Pesados/análise , Doenças Cardiovasculares/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/efeitos adversos , Idoso , Adulto , Distribuição de Poisson , Arsênio/análise , Estudos Cross-OverRESUMO
BACKGROUND: In China, nursing information systems (NIS) implementation can face numerous barriers to acceptance, including the attitudes of potential users. However, few studies have evaluated this acceptance. OBJECTIVE: The aim of this study was to explain the acceptance of NIS utilizing a survey based on unified theory of acceptance and use of technology. METHODS: A multi-center cross-sectional study utilizing an online survey was conducted. SPSS AMOS was used to conduct a structural equation modelling analysis. This research followed the STROBE Checklist. RESULTS: A total of 3973 Nurses participated in the study between January 2023 and March 2023. The acceptance of NIS among nurses was overall moderate to high. The proposed model has been rigorously tested and validated using empirical data, ensuring its credibility and dependability. Performance expectancy (PE), social influence (SI), and attitude significantly and positively affected intentions to use NIS. Effort expectancy (EE) did not show any significant effects in the sample. Facilitating conditions (FCs) was found to have a negative relationship with the intention to use NIS. There was a statistically significant difference BI between the different age groups, working years, and computer training experience. The model demonstrates a good fit with the observed data. CONCLUSIONS: This study identified PE, SI, and attitude as facilitators of nurses' intentions to use NIS. The findings about EE indicates that the ease of using NIS does not seem to be a concern among nurses. Moreover, high FC might be perceived as indicative of a complex system or extensive usage, that can lead to increased workload and reduced behavioural intention (BI). The significant differences in BI among various demographic groups highlight the need for more studies understanding the preferences and barriers faced by different, levels of experience and training backgrounds. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.
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Carbon materials supported Fe-based catalysts possess great potential for the thermal-catalytic hydrogenation of CO2 into valuable chemicals, such as alkenes and oxygenates, due to the excellent active sites' accessibility, appropriate interaction between the active site and carbon support, as well as the excellent capacities in C-O bond activation and C-C bond coupling. Even though tremendous progress has been made to boost the CO2 hydrogenation performance of carbon-supported Fe-based catalysts, e.g., additives modification, the choice of different carbon materials (graphene or carbon nanotubes), electronic property tailoring, etc., the effect of carbon support porosity on the evolution of Fe-based active sites and the corresponding catalytic performance has been rarely investigated. Herein, a series of porous carbon samples with different porosities are obtained by the K2CO3 activation of petroleum pitch under different temperatures. Fe-based active sites and the alkali promoter Na are anchored on the porous carbon to study the effect of carbon support porosity on the physicochemical properties of Fe-based active sites and CO2 hydrogenation performance. Multiple characterizations clarify that the bigger meso/macro-pores in the carbon support are beneficial for the formation of the Fe5C2 crystal phase for C-C bond coupling, therefore boosting the synthesis of C2+ chemicals, especially C2+ alcohols (C2+OH), while the limited micro-pores are unfavorable for C2+ chemicals synthesis owing to the sluggish crystal phase evolution and reactants' inaccessibility. We wish our work could enrich the horizon for the rational design of highly efficient carbon-supported Fe-based catalysts.
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Excessive fluoride can adversely affect bone mineral density (BMD). Oxidative stress and mitochondrial dysfunction are crucial mechanisms of health damage induced by fluoride. Here, a cross-sectional survey involving 907 Chinese farmers (aged 18-60) was carried out in Tongxu County in 2017, aiming to investigate the significance of mitochondrial DNA copy number (mtDNAcn) and oxidative stress in fluoride-related BMD change. Concentrations of urinary fluoride (UF), serum oxidative stress biomarkers, including total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA), as well as relative mtDNAcn in peripheral blood were determined. The multivariable linear model and mediation analysis were performed to assess associations between UF, oxidative stress, and relative mtDNAcn with BMD. Results showed that GSH-Px levels increased by 6.98 U/mL [95% confidence interval (CI) 3.41-10.56)] with each 1.0 mg/L increment of UF. After stratification, the T-AOC, relative mtDNAcn, and BMD decreased by 0.04 mmol/L (-0.08 ~ -0.01), 0.29-unit (-0.55 ~ -0.04), and 0.18-unit (-0.33 ~ -0.03) with every 1.0 mg/L elevation of UF in the excessive fluoride group (EFG, adults with UF > 1.6 mg/L), respectively. Furthermore, T-AOC and relative mtDNAcn were favorably related to the BMD in the EFG (ß = 0.82, 95%CI 0.16-1.48 for T-AOC; ß = 0.11, 95%CI 0.02-0.19 for relative mtDNAcn). Mediation analysis showed that relative mtDNAcn and T-AOC mediated 15.4% and 17.1% of the connection between excessive fluoride and reduced BMD, respectively. Findings suggested that excessive fluoride was related to lower BMD in adults, and the decrement of T-AOC and relative mtDNAcn partially mediate this relationship.
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Densidade Óssea , DNA Mitocondrial , Fazendeiros , Fluoretos , Estresse Oxidativo , Fluoretos/toxicidade , Humanos , Densidade Óssea/efeitos dos fármacos , Adulto , Pessoa de Meia-Idade , Masculino , Estudos Transversais , Adolescente , China , Adulto Jovem , Feminino , Variações do Número de Cópias de DNA , Exposição Ocupacional/efeitos adversos , Biomarcadores/sangueRESUMO
Glucose-6-phosphate dehydrogenase (G6PD) is involved in the catalytic pentose phosphate pathway (PPP), which is closely related to energy metabolism. G6PD plays a crucial role in many types of cancer, but the specific molecular mechanisms of G6PD in cancer remain unclear. Therefore, we investigated the potential oncogenic role of G6PD in various tumors based on The Cancer Genome Atlas (TCGA), the cBioPortal datasets, the University of California Santa Cruz (UCSC) Xena browser, and the UALCAN-based online tool. G6PD was highly expressed in several cancer tissues (hepatocellular carcinoma, glioma, and breast cancer) compared with normal tissues and was significantly associated with poor prognosis of hepatocellular carcinoma, clear cell renal cell carcinoma, and breast cancer. Promoter methylation levels of G6PD were lower in Bladder Urothelial Carcinoma (BLCA) (P = 2.77e-02), breast invasive carcinoma (BRCA) (P = 1.62e-12), kidney renal clear cell carcinoma (KIRC) (P = 4.23e-02), kidney renal papillary cell carcinoma (KIRP) (P = 2.64e-03), liver hepatocellular carcinoma (LIHC) (P = 1.76e-02), stomach adenocarcinoma (STAD) (P = 3.50e-02), testicular germ cell tumors (TGCT) (P = 1.62e-12), higher in prostate adenocarcinoma (PRAD) (P = 1.81e-09), and uterine corpus endometrial carcinoma (UCEC) (P = 2.96e-04) compared with corresponding normal tissue samples. G6PD expression was positively correlated with the infiltration level of immune cells in most tumors, suggesting that G6PD may be involved in tumor immune infiltration. In addition, the functional mechanism of G6PD also involves 'Carbon metabolism', 'Glycolysis/Gluconeogenesis', 'Pentose phosphate pathway', and 'Central carbon pathway metabolism in cancer signaling pathway'. This pan-cancer study provides a relatively broad understanding of the oncogenic role of G6PD in various tumors and presents a theoretical basis for the development of G6PD inhibitors as therapeutic drugs for multiple cancers.
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Adenocarcinoma , Neoplasias da Mama , Carcinoma Hepatocelular , Carcinoma de Células Renais , Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias Hepáticas , Neoplasias da Bexiga Urinária , Humanos , Masculino , Carbono , Carcinogênese , Carcinoma de Células Renais/genética , Glucosefosfato Desidrogenase/genética , Neoplasias Renais/genética , Neoplasias Hepáticas/genética , Pentoses , FosfatosRESUMO
Unravelling belowground strategies is critical for understanding species coexistence and successional dynamics; yet, our knowledge of nutrient acquisition strategies of forest species at different successional stages remains limited. We measured morphological (diameter, specific root length, and root tissue density), architectural (branching ratio), physiological (ammonium, nitrate, and glycine uptake rates) root traits, and mycorrhizal colonisation rates of eight coexisting woody species in an early successional plantation forest in subtropical China. By incorporating physiological uptake efficiency, we revealed a bi-dimensional root economics space comprising of an 'amount-efficiency' dimension represented by morphological and physiological traits, and a 'self-symbiosis' dimension dominated by architectural and mycorrhizal traits. The early pioneer species relied on root-fungal symbiosis, developing densely branched roots with high mycorrhizal colonisation rates for foraging mobile soil nitrate. The late pioneer species invested in roots themselves and allocated effort towards improving uptake efficiency of less-mobile ammonium. Within the root economics space, the covariation of axes with soil phosphorus availability also distinguished the strategy preference of the two successional groups. These results demonstrate the importance of incorporating physiological uptake efficiency into root economics space, and reveal a trade-off between expanding soil physical space exploration and improving physiological uptake efficiency for successional species coexistence in forests.
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Micorrizas , Árvores , Árvores/fisiologia , Raízes de Plantas/fisiologia , Nitratos , Florestas , Micorrizas/fisiologia , SoloRESUMO
BACKGROUND: Norovirus is a leading cause of acute gastroenteritis among children. Previous studies based on symptomatic infections indicated that mutations, rather than recombination drove the evolution of the norovirus ORF2. These characteristics were found in hospital-based symptomatic infections, whereas, asymptomatic infections are frequent and contribute significantly to transmission. METHODS: We conducted the first norovirus molecular epidemiology analysis covering both symptomatic and asymptomatic infections derived from a birth cohort study in the northern China. RESULTS: During the study, 14 symptomatic and 20 asymptomatic norovirus infections were detected in 32 infants. Out of the 14 strains that caused symptomatic infections, 12 strains were identified as GII.3[P12], and others were GII.4[P31]. Conversely, 17 asymptomatic infections were caused by GII.4[P31], two by GII.2[P16], and one by GII.4[P16]. Regardless of symptomatic and asymptomatic infections, the mutations were detected frequently in the ORF2 region, and almost all recombination were identified in the RdRp-ORF2 region. The majority of the mutations were located around the predefined epitope regions of P2 subdomain indicating a potential for immune evasion. CONCLUSION: The role of symptomatic as well as asymptomatic infections in the evolution of norovirus needs to be evaluated continuously.
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Infecções por Caliciviridae , Norovirus , Humanos , Lactente , Infecções Assintomáticas/epidemiologia , Infecções por Caliciviridae/epidemiologia , Estudos de Coortes , População do Leste Asiático , Fezes , Genótipo , Epidemiologia Molecular , Norovirus/genética , FilogeniaRESUMO
RATIONALE: The development of appropriate analytical screening techniques for pharmaceuticals and personal care products (PPCPs) is the basis for studying the distribution and environmental impact of emerging contaminants (ECs). Mass spectrometry-based screening methods vary with the complexity of the target compounds. It is challenging to balance both positive and negative ion quantification with a low detection limit. To establish a set of experimental methods including extraction, chromatography-separation and mass spectrometry screening is one of the most important topics in PPCP research. This paper describes a universal and efficient qualification and quantification protocol for the simultaneous detection of 34 PPCPs in different environmental samples in a single analytical data acquisition run. METHODS: Thirty-four representative PPCPs, which are widely distributed in the environment with high ecological toxicity and complex chemical structures, were selected as representative target ECs. The extraction of the target PPCPs was achieved using only one solid-phase extraction cartridge without the need to adjust the pH of samples. The enriched samples were detected by LC-MS/MS in both positive and negative ion modes simultaneously. The protocol was evaluated based on the accuracy, precision, detection limits and matrix effects. RESULTS: This method achieved simultaneous detection of PPCPs in both positive and negative ion modes, with a single analytical cycle of 12 min. The observed SPE recoveries were between 40% and 115%. The instrumental detection limits (IDL) varied from 0.01 to 1 pg, and the method detection limits (MDL) were between 0.002 and 3.323 ng/l in different matrices. Most of the PPCPs were subjected to matrix suppression below 30%. The method was successfully applied for quantitative analysis of the PPCPs in different environmental samples, including river samples, wastewater treatment plant (WWTP) samples and soil samples. CONCLUSIONS: This protocol developed a rapid and efficient detection method to simultaneous qualitative and quantitative 34 representative PPCPs in the environment. The IDL ranged from 0.01 to 1 pg and the MDL ranged from 0.002 to 3.323 ng/l in different matrices. The detection limit was one order of magnitude lower compared to previous studies. The protocol also provided a wide application range for different environmental matrices, which permitted the migration and transformation of PPCPs to be explored.
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Cosméticos , Poluentes Químicos da Água , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Poluentes Químicos da Água/análise , Cosméticos/análise , Extração em Fase Sólida/métodos , Preparações Farmacêuticas , Monitoramento Ambiental/métodosRESUMO
BACKGROUND: This study presented the mortality trend of ischemic heart disease (IHD) in Chinese residents from 2010 to 2019 and provided a basis for further establishment of relevant interventions. METHODS: Data, such as sex, age, urban and rural areas, and death status, were extracted from the China Death Surveillance Dataset from 2010 to 2019, with mortality and age-adjusted death rates (AADRs) as the main indicators. The joinpoint regression model was used to analyze mortality and AADRs trends in IHD. A semi-structured expert interview was conducted to propose targeted intervention measures and countermeasures. RESULTS: We observed an overall upward trend in IHD mortality rates and AADRs in China from 2010 to 2019 (average annual percentage change [AAPC] = 5.14%, AAPCAADRs = 1.60%, P < 0.001). Mortality rates and AADRs increased for both males (AAPC = 4.91%, AAPCAADRs = 1.09%, P < 0.05) and females (AAPC = 5.57%, AAPCAADRs = 1.84%, P < 0.001), with higher mortality rate for males than females but higher variation for females than males. Urban (AAPC = 4.80%, AAPCAADRs = 1.76%, P < 0.05) and rural (AAPC = 5.31%, P < 0.001; AAPCAADRs = 0.99%, P > 0.05) mortality rates increased, with the mortality rate higher in rural areas than in urban areas. In the age analysis, mortality rate was higher in middle-aged and older adults than in other age groups. The age-sex cross-analysis found the highest trend in mortality rates among females aged ≥ 75 years (annual percentage change [APC] = 2.43%, P < 0.05). CONCLUSIONS: The upward trend in IHD mortality in China from 2010 to 2019, especially among female residents aged ≥ 75 years, poses continuing challenges to public health policies and actions.
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Isquemia Miocárdica , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , China/epidemiologia , Mortalidade , Isquemia Miocárdica/mortalidade , População Rural , População Urbana , População do Leste AsiáticoRESUMO
Microcystin-LR (MC-LR), one of aquatic environmental contaminants with reproductive toxicity produced by cyanobacterial blooms, but its toxic effects and mechanisms on the ovary are not fully understood. Here, proteomic techniques and molecular biology experiments were performed to study the potential mechanism of MC-LR-caused ovarian toxicity. Results showed that protein expression profile of ovarian granulosa cells (KK-1) was changed by 17 µg/mL MC-LR exposure. Comparing with the control group, 118 upregulated proteins as well as 97 downregulated proteins were identified in MC-LR group. Function of differentially expressed proteins was found to be enriched in pathways related to adherent junction, such as cadherin binding, cell-cell junction, cell adhesion and focal adherens. Furthermore, in vitro experiments, MC-LR significantly downregulated the expression levels of proteins associated with adherent junction (ß-catenin, N-cadherin, and α-catenin) as well as caused cytoskeletal disruption in KK-1 cells (P < 0.05), indicating that the adherent junction was damaged. Results of in vivo experiments have shown that after 14 days of acute MC-LR exposure (40 µg/kg), damaged adherent junction and an increased number of atretic follicles were observed in mouse ovaries. Moreover, MC-LR activated JNK, an upstream regulator of adherent junction proteins, in KK-1 cells and mouse ovarian tissues. In contrast, JNK inhibition alleviated MC-LR-induced adherent junction damage in vivo and in vitro, as well as the number of atretic follicles. Taken together, findings from the present study indicated that JNK is involved in MC-LR-induced granulosa cell adherent junction damage, which accelerated follicular atresia. Our study clarified a novel mechanism of MC-LR-caused ovarian toxicity, providing a theoretical foundation for protecting female reproductive health from environmental pollutants.
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Atresia Folicular , Proteômica , Animais , Feminino , Camundongos , Células da Granulosa , Microcistinas/toxicidade , MAP Quinase Quinase 4/metabolismoRESUMO
Dental fluorosis (DF) is a widely prevalent disease caused by excessive fluoride with limited awareness of its underlying pathogenesis. Here, a pilot population study was conducted to explore the pathogenesis of DF from the perspective of intestinal microbiome changes, and verified it in animal experiments combining intestinal microbiome and metabolomics. A total of 23 children were recruited in 2017 in China and divided into DF (n = 9) and control (n = 14) groups (DFG and CG, respectively). The SD rat model was established by drinking water containing sodium fluoride (NaF). Gut microbiome profiles of children and rats were analyzed by16S rDNA V3-V4 sequencing, and the intestinal metabolomics analysis of rats was performed by LC-MS methods. The 16 S rDNA sequencing revealed that the gut microbiome composition was significantly perturbed in children in DFG compared to that in CG. Acidobacteria and Thermi were specifically observed in DFG and CG, respectively. Besides, 15 fecal microbiotas were significantly altered at the genus level in DFG. Furthermore, only the expression of annotated genes for pentose and glucuronate interconversion pathway was significant lower in DFG than that in CG (P = 0.04). Notably, in NaF-treated rats, we also observed the changes of some key components of pentose and glucuronate interconversion pathway at the level of microorganisms and metabolites. Our findings suggested that the occurrence of DF is closely related to the alteration of intestinal microorganisms and metabolites annotated in the pentose and glucuronate interconversion pathway.
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Fluorose Dentária , Ratos , Animais , Fluorose Dentária/genética , Fluorose Dentária/epidemiologia , Ratos Sprague-Dawley , Metabolômica/métodos , Fluoretos , Fluoreto de SódioRESUMO
Fluorosis is a serious global public health problem. Interestingly, so far, there is no specific drug treatment for the treatment of fluorosis. In this paper, the potential mechanisms of 35 ferroptosis-related genes in U87 glial cells exposed to fluoride were explored by bioinformatics methods. Significantly, these genes are involved in oxidative stress, ferroptosis, and decanoate CoA ligase activity. Ten pivotal genes were found by the Maximal Clique Centrality (MCC) algorithm. Furthermore, according to the Connectivity Map (CMap) and the Comparative Toxicogenomics Database (CTD), 10 possible drugs for fluorosis were predicted and screened, and a drug target ferroptosis-related gene network was constructed. Molecular docking was used to study the interaction between small molecule compounds and target proteins. Molecular dynamics (MD) simulation results show that the structure of the Celestrol-HMOX1 composite is stable and the docking effect is the best. In general, Celastrol and LDN-193189 may target ferroptosis-related genes to alleviate the symptoms of fluorosis, which may be effective candidate drugs for the treatment of fluorosis.
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Ferroptose , Fluoretos , Fluorose Dentária , Algoritmos , Biologia Computacional , Bases de Dados Factuais , Ferroptose/genética , Simulação de Acoplamento Molecular , Humanos , Linhagem Celular , Fluoretos/efeitos adversosRESUMO
To examine the association between fluoride exposure and childhood blood pressure (BP), we used data involving 3260 subjects participating in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016. Both plasma and water fluoride concentrations were measured using the ion-specific electrode. Outcome variables were systolic blood pressure (SBP) and diastolic blood pressure (DBP). For a 1-mg/L increase in water fluoride concentration, the participants' SBP decreased by 0.473 mm Hg (95% CI: -0.860, -0.087). Specifically, inverse associations were found between water fluoride and SBP in girls (ß= -0.423, 95% CI: -0.886, -0.021), adolescents (ß= -0.623, 95% CI: -0.975, -0.272), and non-Hispanic whites (ß= -0.694, 95% CI: -1.237, -0.151). Also, every 1-µmol/L increase in plasma fluoride concentration was associated with a 1.183 mm Hg decrease in SBP among other races (95% CI: -2.258, -0.108). This study suggested that fluoride exposure may affect childhood blood pressure.
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Fluoretos , Água , Feminino , Humanos , Criança , Adolescente , Estados Unidos , Pressão Sanguínea/fisiologia , Fluoretos/toxicidade , Inquéritos NutricionaisRESUMO
The root economics space (RES) is multidimensional and largely shaped by belowground biotic and abiotic influences. However, how root-fungal symbioses and edaphic fertility drive this complexity remains unclear. Here, we measured absorptive root traits of 112 tree species in temperate and subtropical forests of China, including traits linked to functional differences between arbuscular mycorrhizal (AM) and ectomycorrhizal (ECM) hosts. Our data, from known mycorrhizal tree species, revealed a 'fungal-symbiosis' dimension distinguishing AM from ECM species. This divergence likely resulted from the contrasting mycorrhizal evolutionary development of AM vs ECM associations. Increased root tissue cortical space facilitates AM symbiosis, whereas increased root branching favours ECM symbiosis. Irrespective of mycorrhizal type, a 'root-lifespan' dimension reflecting aspects of root construction cost and defence was controlled by variation in specific root length and root tissue density, which was fully independent of root nitrogen content. Within this function-based RES, we observed a substantial covariation of axes with soil phosphorus and nitrate levels, highlighting the role played by these two axes in nutrient acquisition and conservation. Overall, our findings demonstrate the importance of evolved mycorrhizal symbiosis pathway and edaphic fertility in framing the RES, and provide theoretical and mechanistic insights into the complexity of root economics.
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Micorrizas , Fertilidade , Raízes de Plantas/metabolismo , Solo , Microbiologia do Solo , Simbiose , ÁrvoresRESUMO
BACKGROUND: Air pollution and previous abortion have been reported to be related to preterm birth (PTB). But rare study examined the effect of air pollution on PTB risk among mothers with previous abortion. OBJECTIVE: To estimate the effect of air pollution on PTB and the potential effect modification of previous abortion on such an association in rural part of Henan province (China). METHOD: Based on National Free Preconception Health Examination Project (NFPHEP), information from the medical records of 57,337 mothers with previous abortion were obtained. An inverse distance-weighted model was used to estimate exposure levels of air pollutants. The effect of air pollution on the risk of PTB was estimated with a multiple logistic regression model. Stratified and interaction analyses were undertaken to explore the potential effect modification of previous abortion on this association. RESULTS: The risk of PTB was positively associated with exposure to levels of nitrogen dioxide (NO2; OR: 1.03; 95%CI: 1.02-1.04)], and sulfur dioxide (SO2; 1.04; 1.02-1.07), and negatively associated with ozone (O3) exposure (0.97; 0.97-0.98) during the entire pregnancy. Besides, we observed a positive effect of carbon monoxide (CO) exposure during the third trimester of pregnancy on PTB (1.14; 1.01-1.29). The type of previous abortion could modify the effect of air pollution on the PTB risk (P-interaction < 0.05). Compared with mothers with previous induced abortion, mothers with previous spontaneous abortion carried a higher risk of PTB induced by NO2, CO, and O3. CONCLUSIONS: The risk of PTB was positively associated with levels of NO2, SO2 and CO, and negatively associated with the O3 level. The types of previous abortion could modify the effect of air pollution on PTB. Mothers who had an abortion previously, especially spontaneous abortion, should avoid exposure to air pollution to improve their pregnancy outcome.
Assuntos
Aborto Induzido , Aborto Espontâneo , Poluentes Atmosféricos , Poluição do Ar , Nascimento Prematuro , Aborto Induzido/estatística & dados numéricos , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , China/epidemiologia , Feminino , Humanos , Recém-Nascido , Exposição Materna/efeitos adversos , Exposição Materna/estatística & dados numéricos , Dióxido de Nitrogênio/análise , Dióxido de Nitrogênio/toxicidade , Material Particulado/análise , Material Particulado/toxicidade , Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologiaRESUMO
Common cold is usually considered to be associated with outdoor climate, but the evidence linking with indoor environmental factors is lacking. The role of indoor renovations during which critical timing window on childhood common cold remains unclear. Therefore, we investigated the effect of exposure to new furniture and/or redecoration during prenatal and postnatal periods on the occurrence and duration of common cold in preschool children. We conducted a retrospective cohort study of 39 782 children aged 3-6 years in seven cities of China. The occurrence and duration of common cold in children, and their lifetime exposures to indoor new furniture and redecoration (including pregnancy, the first year of life, and after one year old) were assessed using a questionnaire administered by the parents. Associations between high frequency (>5 colds) and long duration (≥2 weeks per cold) of common cold during past 12 months and exposure to indoor new furniture/redecoration were examined by logistic regression models in terms of odds ratio (OR) and 95% confidence interval (CI). We found that the prevalence of high frequency and long duration of common cold in preschool children in China were, respectively, 9.2% and 11.9%. Frequent common cold was significantly associated with exposure to indoor new furniture/redecoration during pregnancy, first year, and after 1 year old, respectively, with the ORs (95% CI) = 1.25 (1.12-1.39), 1.11 (1.00-1.25), and 1.09 (1.01-1.18). Furthermore, childhood long duration per cold was associated with exposure to indoor new furniture/redecoration during pregnancy with OR (95% CI) of 1.14 (1.03-1.25) but not with postnatal exposure. We identified that prenatal exposure to home renovation was more critical than postnatal exposure for an increased risk of high frequency and long duration of common cold. Sensitivity analysis showed that the association between prenatal exposure to indoor renovations and the risk of childhood common cold was consistent and robust, and the associations were modified by some personal and indoor environmental factors. Our findings indicated that prenatal and postnatal exposure to home renovation played an important role in the risk of childhood common cold, supporting the hypothesis of "fetal origin of childhood infection."
Assuntos
Poluição do Ar em Ambientes Fechados , Resfriado Comum , Efeitos Tardios da Exposição Pré-Natal , Poluição do Ar em Ambientes Fechados/análise , Pré-Escolar , China/epidemiologia , Resfriado Comum/epidemiologia , Exposição Ambiental , Feminino , Humanos , Lactente , Gravidez , Estudos Retrospectivos , Fatores de RiscoRESUMO
Fluoride is widely distributed, and excessive intake will lead to dental fluorosis. In this study, six offspring rats administrated 100 mg/L sodium fluoride were defined as the dental fluorosis group, and eight offspring rats who received pure water were defined as the control group. Differentially expressed proteins and metabolites extracted from peripheral blood were identified using the liquid chromatography tandem mass spectrometry and gas chromatography mass spectrometry, with the judgment criteria of fold change >1.2 or <0.83 and p < 0.05. A coexpression enrichment analysis using OmicsBean was conducted on the identified proteins and metabolites, and a false discovery rate (FDR) < 0.05 was considered significant. Human Protein Atlas was used to determine the subcellular distribution of hub proteins. The Gene Cards was used to verify results. A total of 123 up-regulated and 46 down-regulated proteins, and 12 up-regulated and 2 down-regulated metabolites were identified. The significant coexpression pathways were the HIF-1 (FDR = 1.86 × 10−3) and glycolysis/gluconeogenesis (FDR = 1.14 × 10−10). The results of validation analysis showed the proteins related to fluorine were mainly enriched in the cytoplasm and extrinsic component of the cytoplasmic side of the plasma membrane. The HIF-1 pathway (FDR = 1.01 × 10−7) was also identified. Therefore, the HIF-1 and glycolysis/gluconeogenesis pathways were significantly correlated with dental fluorosis.