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1.
Mol Cell ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38838666

RESUMO

Circular RNAs (circRNAs) are upregulated during neurogenesis. Where and how circRNAs are localized and what roles they play during this process have remained elusive. Comparing the nuclear and cytoplasmic circRNAs between H9 cells and H9-derived forebrain (FB) neurons, we identify that a subset of adenosine (A)-rich circRNAs are restricted in H9 nuclei but exported to cytosols upon differentiation. Such a subcellular relocation of circRNAs is modulated by the poly(A)-binding protein PABPC1. In the H9 nucleus, newly produced (A)-rich circRNAs are bound by PABPC1 and trapped by the nuclear basket protein TPR to prevent their export. Modulating (A)-rich motifs in circRNAs alters their subcellular localization, and introducing (A)-rich circRNAs in H9 cytosols results in mRNA translation suppression. Moreover, decreased nuclear PABPC1 upon neuronal differentiation enables the export of (A)-rich circRNAs, including circRTN4(2,3), which is required for neurite outgrowth. These findings uncover subcellular localization features of circRNAs, linking their processing and function during neurogenesis.

2.
Water Res X ; 22: 100216, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38831973

RESUMO

The performance of partial nitritation (PN)-moving bed biofilm reactor (MBBR) in removal of antibiotics in the sidestream wastewater has not been investigated so far. In this work, the removal of ciprofloxacin was assessed under varying free nitrous acid (FNA) levels and different trophic modes. For the first time, a positive correlation was observed between ciprofloxacin removal and FNA levels, either in the autotrophic PN-MBBR or in the mixotrophic PN-MBBR, mainly ascribed to the FNA-stimulating effect on heterotrophic bacteria (HB)-induced biodegradation. The maximum ciprofloxacin removal efficiency (∼98 %) and removal rate constant (0.021 L g-1 SS h-1) were obtained in the mixotrophic PN-MBBR at an average FNA level of 0.056 mg-N L-1, which were 5.8 and 51.2 times higher than the corresponding values in the autotrophic PN-MBBR at 0 mg FNA-N L-1. Increasing FNA from 0.006 to 0.056 mg-N L-1 would inhibit ammonia oxidizing bacteria (AOB)-induced cometabolism and metabolism from 10.2 % and 6.9 % to 6.2 % and 6.4 %, respectively, while HB-induced cometabolism and metabolism increased from 31.2 % and 22.7 % to 41.9 % and 34.5 %, respectively. HB-induced cometabolism became the predominant biodegradation pathway (75.9 %-85.8 %) in the mixotrophic mode. Less antimicrobial biotransformation products without the piperazine or fluorine were newly identified to propose potential degradation pathways, corresponding to microbial-induced metabolic types and FNA levels. This work shed light on enhancing antibiotic removal via regulating both FNA accumulation and organic carbon addition in the PN-MBBR process treating sidestream wastewater.

3.
BMC Psychiatry ; 24(1): 377, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773436

RESUMO

BACKGROUND: The adolescent depression associated with childhood trauma has been confirmed, but the underlying mechanisms remain unclear. This study aims to explore the chain-mediated role of borderline personality traits and self-control in the relationship between childhood trauma and adolescent depression. METHODS: A cross-sectional study was conducted on 2,664 students from a senior high school through online questionnaires from October to December 2022 in Henan, China. Childhood Trauma Questionnaire-Short Form, Borderline Personality Dimension of Personality Diagnostic Questionnaire-4, Self-Control Scale, and Children's Depression Inventory were used to measure childhood trauma, borderline personality traits, and self-control. RESULTS: The prevalence of depression in adolescents was 21.17%, while the prevalence of borderline personality was 12.00%. childhood trauma (r = 0.50, p < 0.001) and borderline personality traits (r = 0.60, p < 0.001) were positively correlated with adolescent depressive symptoms, while self-control was negatively correlated with depressive symptoms (r = - 0.50, p < 0.001). Borderline personality traits and Self-control both play a mediating role in childhood trauma and depressive symptoms, and the mediating effect values are 0.116 (95%CI = [0.098, 0.137]), and 0.022 (95%CI = [0.012, 0.032]) respectively. The chain mediating effect of borderline personality traits and self-control on the relationship between childhood trauma and depressive symptoms was significant (effect value: 0.034, 95%CI = [0.028, 0.042]). CONCLUSIONS: Childhood trauma can predict depressive symptoms in adolescents due to the formation of borderline personality traits and the reduction of self-control. These findings are important for understanding the formation of personality traits, self-control abilities and coping strategies shaped by traumatic experiences in adolescents.


Assuntos
Experiências Adversas da Infância , Transtorno da Personalidade Borderline , Depressão , Autocontrole , Humanos , Adolescente , Feminino , Masculino , Transtorno da Personalidade Borderline/psicologia , Transtorno da Personalidade Borderline/epidemiologia , Estudos Transversais , Depressão/psicologia , Depressão/epidemiologia , Experiências Adversas da Infância/psicologia , Autocontrole/psicologia , China/epidemiologia , Prevalência , Inquéritos e Questionários
4.
Front Nutr ; 11: 1377910, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38784137

RESUMO

Background: Frailty is a complex clinical syndrome characterized by a decline in the functioning of multiple body systems and reduced adaptability to external stressors. Dietary ω-3 fatty acids are considered beneficial dietary nutrients for preventing frailty due to their anti-inflammatory and immune-regulating properties. However, previous research has yielded conflicting results, and the association between ω-6 fatty acids, the ω-6: ω-3 ratio, and frailty remains unclear. This study aims to explore the relationship between these factors using the National Health and Nutrition Examination Survey (NHANES) database. Materials and methods: Specialized weighted complex survey design analysis software was employed to analyze data from the 2005-2014 NHANES, which included 12,315 participants. Multivariate logistic regression models and restricted cubic splines (RCS) were utilized to assess the relationship between omega intake and frailty risk in all participants. Additionally, a nomogram model for predicting frailty risk was developed based on risk factors. The reliability of the clinical model was determined by the area under the receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA). Results: In dietary ω-3 intake, compared to the T1 group (≤1.175 g/d), the T3 group's intake level (>2.050 g/d) was associated with approximately 17% reduction in frailty risk in model 3, after rigorous covariate adjustments (odds ratio (OR) = 0.83, 95% confidence interval (CI): (0.70, 0.99)). In dietary ω-6 intake, the T2 group's intake level (>11.423, ≤19.160 g/d) was associated with a 14% reduction in frailty risk compared to the T1 group (≤11.423 g/d) (OR: 0.86, 95% CI: 0.75, 1.00, p = 0.044). RCS results indicated a non-linear association between ω-3 and ω-6 intake and frailty risk. Both ROC and DCA curves demonstrated the stability of the constructed model and the effectiveness of an omega-rich diet in reducing frailty risk. However, we did not find a significant association between the ω-6: ω-3 ratio and frailty. Conclusion: This study provides support for the notion that a high intake of ω-3 and a moderate intake of ω-6 may contribute to reducing frailty risk in middle-aged and elderly individuals.

5.
Nat Biotechnol ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653797

RESUMO

Efforts to advance RNA aptamers as a new therapeutic modality have been limited by their susceptibility to degradation and immunogenicity. In a previous study, we demonstrated synthesized short double-stranded region-containing circular RNAs (ds-cRNAs) with minimal immunogenicity targeted to dsRNA-activated protein kinase R (PKR). Here we test the therapeutic potential of ds-cRNAs in a mouse model of imiquimod-induced psoriasis. We find that genetic supplementation of ds-cRNAs leads to inhibition of PKR, resulting in alleviation of downstream interferon-α and dsRNA signals and attenuation of psoriasis phenotypes. Delivery of ds-cRNAs by lipid nanoparticles to the spleen attenuates PKR activity in examined splenocytes, resulting in reduced epidermal thickness. These findings suggest that ds-cRNAs represent a promising approach to mitigate excessive PKR activation for therapeutic purposes.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38634868

RESUMO

PURPOSE: Postpartum depression (PPD) brings adverse and serious consequences to both new parents and newborns. Neuroticism affects PPD, which remains controversial for confounding factors and reverse causality in cross-sectional research. Therefore, mendelian randomization (MR) study has been adopted to investigate their causal relationship. METHODS: This study utilized large-scale genome-wide association study genetic pooled data from three major databases: the United Kingdom Biobank, the European Bioinformatics Institute, and the FinnGen databases. The causal analysis methods used inverse variance weighting (IVW). The weighted median, MR-Egger method, MR-PRESSO test, and the leave-one-out sensitivity test have been used to examine the results' robustness, heterogeneity, and horizontal pleiotropy. The fixed effect model yielded the results of meta-analysis. RESULTS: In the IVW model, a meta-analysis of the MR study showed that neuroticism increased the risk of PPD (OR, 1.17; 95% CI, 1.11-1.25, p < 0.01). Reverse analysis showed that PPD could not genetically predict neuroticism. There was no significant heterogeneity or horizontal pleiotropy bias in this result. CONCLUSION: Our study suggests neuroticism is the risk factor for PPD from a gene perspective and PPD is not the risk factor for neuroticism. This finding may provide new insights into prevention and intervention strategies for PPD according to early detection of neuroticism.

7.
Sci Total Environ ; 928: 172440, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38614328

RESUMO

Ammonium removal by a symbiosis system of algae (Chlorella vulgaris) and nitrifying bacteria was evaluated in a long-term photo-sequencing batch reactor under varying influent inorganic carbon (IC) concentrations (15, 10, 5 and 2.5 mmol L-1) and different nitrogen loading rate (NLR) conditions (270 and 540 mg-N L-1 d-1). The IC/N ratios provided were 2.33, 1.56, 0.78 and 0.39, respectively, for an influent NH4+-N concentration of 90 mg-N L-1 (6.43 mmol L-1). The results confirmed that both ammonium removal and N2O production were positively related with IC concentration. Satisfactory ammonium removal efficiencies (>98 %) and rates (29-34 mg-N gVSS-1 h-1) were achieved regardless of NLR levels under sufficient IC of 10 and 15 mmol L-1, while insufficient IC at 2.5 mmol L-1 led to the lowest ammonium removal rates of 0 mg-N gVSS-1 h-1. The ammonia oxidation process by ammonia oxidizing bacteria (AOB) played a predominant role over the algae assimilation process in ammonium removal. Long-time IC deficiency also resulted in the decrease in biomass and pigments of algae and nitrifying bacteria. IC limitation led to the decreasing N2O production, probably due to its negative effect on ammonia oxidation by AOB. The optimal IC concentration was determined to be 10 mmol L-1 (i.e., IC/N of 1.56, alkalinity of 500 mg CaCO3 L-1) in the algae-bacteria symbiosis reactor, corresponding to higher ammonia oxidation rate of ∼41 mg-N gVSS-1 h-1 and lower N2O emission factor of 0.13 %. This suggests regulating IC concentrations to achieve high ammonium removal and low carbon emission simultaneously in the algae-bacteria symbiosis wastewater treatment process.


Assuntos
Compostos de Amônio , Carbono , Nitrificação , Simbiose , Carbono/metabolismo , Compostos de Amônio/metabolismo , Eliminação de Resíduos Líquidos/métodos , Bactérias/metabolismo , Chlorella vulgaris/metabolismo , Óxido Nitroso/metabolismo , Reatores Biológicos , Poluentes Químicos da Água/metabolismo , Nitrogênio/metabolismo
8.
Chemosphere ; 353: 141580, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38430943

RESUMO

Information on biotransformation of antivirals in the side-stream partial nitritation (PN) process was limited. In this study, a side-stream PN sludge was adopted to investigate favipiravir biotransformation under controlled ammonium and pH levels. Results showed that free nitrous acid (FNA) was an important factor that inhibited ammonia oxidation and the cometabolic biodegradation of favipiravir induced by ammonia oxidizing bacteria (AOB). The removal efficiency of favipiravir reached 12.6% and 35.0% within 6 days at the average FNA concentrations of 0.07 and 0.02 mg-N L-1, respectively. AOB-induced cometabolism was the sole contributing mechanism to favipiravir removal, excluding AOB-induced metabolism and heterotrophic bacteria-induced biodegradation. The growth of Escherichia coli was inhibited by favipiravir, while the AOB-induced cometabolism facilitated the alleviation of the antimicrobial activities with the formed transformation products. The biotransformation pathways were proposed based on the roughly identified structures of transformation products, which mainly involved hydroxylation, nitration, dehydrogenation and covalent bond breaking under enzymatic conditions. The findings would provide insights on enriching AOB abundance and enhancing AOB-induced cometabolism under FNA stress when targeting higher removal of antivirals during the side-stream wastewater treatment processes.


Assuntos
Amidas , Compostos de Amônio , Pirazinas , Esgotos , Amônia/toxicidade , Amônia/metabolismo , Rios , Oxirredução , Ácido Nitroso , Biotransformação , Antivirais/toxicidade , Reatores Biológicos , Nitritos
9.
Sci Total Environ ; 924: 171517, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38461985

RESUMO

Shrubs have developed various mechanisms for soil phosphorus utilization. Shrub encroachment caused by climate warming alters organic phosphorus mineralization capability by promoting available phosphorus absorption and mediating root exudates. However, few studies have explored how warming regulates the effects of dominant shrubs on soil organic phosphorus mineralization capability. We provide insights into warming, dominant shrub removal, and their interactive effects on the soil organic phosphorus mineralization potential in the Qinghai-Tibetan Plateau. Real-time polymerase chain reaction was used to quantify the soil microbial phosphatase genes (phoC and phoD), which can characterize the soil organic phosphate mineralization potential. We found that warming had no significant effect on the soil organic phosphate-mineralized components (total phosphate, organic phosphate, and available phosphate), genes (phoC and phoD), or enzymes (acid and alkaline phosphatases). Shrub removal negatively influenced the organic phosphate-mineralized components and genes. It significantly decreased soil organic phosphate mineralization gene copy numbers only under warming conditions. Warming increased fungal richness and buffered the effects of shrub removal on bacterial richness and gene copy numbers. However, the change in the microbial community was not the main factor affecting organic phosphate mineralization. We found only phoC copy number had significant correlation to AP. Structural equation modelling revealed that shrub removal and the interaction between warming and shrub removal had a negative direct effect on phoC copy numbers. We concluded that warming increases the negative effect of shrub removal on phosphorus mineralization potential, providing a theoretical basis for shrub encroachment on soil phosphate mineralization under warming conditions.


Assuntos
Bactérias , Fósforo , Fósforo/análise , Solo/química , Fosfatos/análise , Organofosfatos , Microbiologia do Solo
10.
Sci Total Environ ; 923: 171479, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38458444

RESUMO

The effects of five antibiotics (i.e., ampicillin, streptomycin, carbenicillin, kanamycin and tetracycline) on ammonia-oxidizing archaea (AOA) enrichment from anoxic activated sludge were investigated. The combined use of five antibiotics during 90-day cultivation could selectively inhibit nitrite-oxidizing bacteria (NOB) and ammonia-oxidizing bacteria (AOB) with AOA unaffected, as evidenced by the nitrite accumulation ratio of 100 % and the proportion of AOA in ammonia-oxidizing microbes over 91 %. The alternative use of five antibiotics was the optimal approach to screening for AOA during 348-day cultivation, which inhibited AOB growth at a level equivalent to the combined use of five antibiotics (the AOB-amoA gene decreased by over 99.90 %), further promoted AOA abundance (the much higher AOA-amoA to AOB-amoA gene copy number ratio (1453.30) than that in the groups with the combined use of five antibiotics (192.94)), eliminated bacterial adaptation to antibiotics and reduced antibiotic-resistant bacteria to form Nitrocosmicus-dominant community (42.35 % in abundance).


Assuntos
Amônia , Archaea , Archaea/genética , Antibacterianos , Nitritos , Oxirredução , Bactérias/genética , Filogenia , Microbiologia do Solo
11.
Front Endocrinol (Lausanne) ; 15: 1272314, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455653

RESUMO

Background: Low levels of high-density lipoprotein cholesterol (HDL-C) are commonly seen in patients with type 2 diabetes mellitus (T2DM). However, it is unclear whether there is an independent or causal link between HDL-C levels and T2DM. This study aims to address this gap by using the The National Health and Nutrition Examination Survey (NHANES) database and Mendelian randomization (MR) analysis. Materials and methods: Data from the NHANES survey (2007-2018) with 9,420 participants were analyzed using specialized software. Logistic regression models and restricted cubic splines (RCS) were used to assess the relationship between HDL-C and T2DM incidence, while considering covariates. Genetic variants associated with HDL-C and T2DM were obtained from genome-wide association studies (GWAS), and Mendelian randomization (MR) was used to evaluate the causal relationship between HDL-C and T2DM. Various tests were conducted to assess pleiotropy and outliers. Results: In the NHANES study, all groups, except the lowest quartile (Q1: 0.28-1.09 mmol/L], showed a significant association between HDL-C levels and reduced T2DM risk (all P < 0.001). After adjusting for covariates, the Q2 [odds ratio (OR) = 0.67, 95% confidence interval (CI): (0.57, 0.79)], Q3 [OR = 0.51, 95% CI: (0.40, 0.65)], and Q4 [OR = 0.29, 95% CI: (0.23, 0.36)] groups exhibited average reductions in T2DM risk of 23%, 49%, and 71%, respectively. In the sensitivity analysis incorporating other lipid levels, the Q4 group still demonstrates a 57% reduction in the risk of T2DM. The impact of HDL-C levels on T2DM varied with age (P for interaction = 0.006). RCS analysis showed a nonlinear decreasing trend in T2DM risk with increasing HDL-C levels (P = 0.003). In the MR analysis, HDL-C levels were also associated with reduced T2DM risk (OR = 0.69, 95% CI = 0.52-0.82; P = 1.41 × 10-13), and there was no evidence of pleiotropy or outliers. Conclusion: This study provides evidence supporting a causal relationship between higher HDL-C levels and reduced T2DM risk. Further research is needed to explore interventions targeting HDL-C levels for reducing T2DM risk.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , HDL-Colesterol/genética , Fatores de Risco , Análise da Randomização Mendeliana , Inquéritos Nutricionais , Triglicerídeos , Estudo de Associação Genômica Ampla , LDL-Colesterol/genética
12.
Chemosphere ; 353: 141535, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38403121

RESUMO

Recovering resources from wastewater to alleviate the energy crisis has become the prevailing trend of technological development. Purple phototrophic bacteria (PPB), a group of fast-growing microbes, have been widely noticed for their potential in producing value-added products from waste streams. However, saline contents in these waste streams, such as food processing wastewater pose a big challenge, which not only restrain the pollutant removal efficiency, but also hinder the growth of functional microbes. To overcome this, a photo anaerobic membrane bioreactor cultivating PPB (PPB-MBR) was constructed and its performance upon long-term salinity stress was investigated. PPB-MBR achieved desirable pollutants removal performance with the average COD and NH4+ removal efficiency being 87% (±8%, n = 87) and 89% (±10%, n = 87), respectively during long-term exposure to salinity stress of 1-80 g NaCl L-1. PPB were predominant during the entire operation period of 87 days (60%-80%), obtaining maximum biomass yield of 0.67 g biomass g-1 CODremoved and protein productivity of 0.18 g L-1 d-1 at the salinity level of 20 g NaCl L-1 and 60 g NaCl L-1, respectively. The sum of value-added products in proportion to the biomass reached 58% at maximum at the salinity level of 60 g NaCl L-1 with protein, pigments and trehalose contributing to 44%, 8.7%, and 5%, respectively. Based on economic analysis, the most cost-saving scenario treating food processing wastewater was revealed at salinity level of around 20 g NaCl L-1. However, more optimization tools are needed to boost the production efficiency so that the profit from value-added products can outweigh the additional cost by excess salinity in the future implication.


Assuntos
Poluentes Ambientais , Águas Residuárias , Proteobactérias , Eliminação de Resíduos Líquidos , Bactérias , Cloreto de Sódio , Reatores Biológicos/microbiologia , Bactérias Anaeróbias , Salinidade
13.
Environ Sci Technol ; 58(11): 5162-5173, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38358933

RESUMO

Sidestream serves as an important reservoir collecting pharmaceuticals from sludge. However, the knowledge on sidestream pharmaceutical removal is still insufficient. In this work, atenolol biodegradation during sidestream partial nitritation (PN) processes characterized by high free nitrous acid (FNA) accumulation was modeled. To describe the FNA inhibition on ammonia oxidation and atenolol removal, Vadivelu-type and Hellinga-type inhibition kinetics were introduced into the model framework. Four inhibitory parameters along with four biodegradation kinetic parameters were calibrated and validated separately with eight sets of batch experimental data and 60 days' PN reactor operational data. The developed model could accurately reproduce the dynamics of nitrogen and atenolol. The model prediction further revealed that atenolol biodegradation efficiencies by ammonia-oxidizing bacteria (AOB)-induced cometabolism, AOB-induced metabolism, and heterotrophic bacteria-induced biodegradation were 0, ∼ 60, and ∼35% in the absence of ammonium and FNA; ∼ 14, ∼ 29, and ∼28% at 0.03 mg-N L-1 FNA; and 7, 15, and 5% at 0.19 mg-N L-1 FNA. Model simulation showed that the nitritation efficiency of ∼99% and atenolol removal efficiency of 57.5% in the PN process could be achieved simultaneously by controlling pH at 8.5, while 89.2% total nitrogen and 57.1% atenolol were removed to the maximum at pH of 7.0 in PN coupling with the anammox process. The pH-based operational strategy to regulate FNA levels was mathematically demonstrated to be effective for achieving the simultaneous removal of nitrogen and atenolol in PN-based sidestream processes.


Assuntos
Compostos de Amônio , Ácido Nitroso , Atenolol , Amônia/metabolismo , Nitrogênio/metabolismo , Oxirredução , Reatores Biológicos/microbiologia , Esgotos , Nitritos
14.
Biotechnol J ; 19(2): e2300410, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38375559

RESUMO

Site-specific integration (SSI) via recombinase mediated cassette exchange (RMCE) has shown advantages over random integration methods for expression of biotherapeutics. As an extension of our previous work developing SSI host cells, we developed a dual-site SSI system having two independent integration sites at different genomic loci, each containing a unique landing pad (LP). This system was leveraged to generate and compare two RMCE hosts, one (dFRT) compatible with the Flp recombinase, the other (dBxb1) compatible with the Bxb1 recombinase. Our comparison demonstrated that the dBxb1 host was able to generate stable transfectant pools in a shorter time frame, and cells within the dBxb1 transfectant pools were more phenotypically and genotypically stable. We further improved process performance of the dBxb1 host, resulting in desired fed batch performance attributes. Clones derived from this improved host (referred as 41L-11) maintained stable expression profiles over extended generations. While the data represents a significant improvement in the efficiency of our cell line development process, the dual LP architecture also affords a high degree of flexibility for development of complex protein modalities.


Assuntos
Genômica , Recombinases , Cricetinae , Animais , Células CHO , Cricetulus , Recombinases/genética , Células Clonais/metabolismo , Genômica/métodos , Transgenes
15.
Acta Neurol Belg ; 124(2): 485-494, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37889424

RESUMO

BACKGROUND: The use of circulating lipid traits as biomarkers to predict the risk of amyotrophic lateral sclerosis (ALS) is currently controversial, and the evidence-based medical evidence for the use of lipid-lowering agents, especially statins, on ALS risk remains insufficient. Our aim was to apply a Mendelian randomization (MR) approach to assess the causal impact of lipid-lowering agents and circulating lipid traits on ALS risk. MATERIALS AND METHODS: Our study included primary and secondary analyses, in which the risk associations of lipid-lowering gene inhibitors, lipid traits, and ALS were assessed by the inverse variance weighting method as the primary approach. The robustness of the results was assessed using LDSC assessment, conventional MR sensitivity analysis, and used Mediating MR to explore potential mechanisms of occurrence. In the secondary analysis, the association of lipid-lowering genes with ALS was validated using the Summary data-based Mendelian Randomization (SMR) method. RESULTS: Our results showed strong evidence between genetic proxies for Apolipoprotein B (ApoB) inhibitor (OR = 0.76, 95% CI = 0.68 - 0.86; P = 5.58 × 10-6) and reduced risk of ALS. Additionally, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitor (OR = 1.06, 95% CI = 0. 85-1.33) was not found to increase ALS risk. SMR results suggested that ApoB expression was associated with increased ALS risk, and colocalization analysis did not support a significant common genetic variation between ApoB and ALS. Mediator MR analysis suggested a possible mediating role for interleukin-6 and low-density lipoprotein cholesterol (LDL-C). While elevated LDL-C was significantly associated with increased risk of ALS among lipid traits, total cholesterol (TC) and ApoB were weakly associated with ALS. LDSC results suggested a potential genetic correlation between these lipid traits and ALS. CONCLUSIONS: Using ApoB inhibitor can lower the risk of ALS, statins do not trigger ALS, and LDL-C, TC, and ApoB levels can predict the risk of ALS.


Assuntos
Esclerose Lateral Amiotrófica , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , LDL-Colesterol/genética , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Esclerose Lateral Amiotrófica/genética , Análise da Randomização Mendeliana , Apolipoproteínas B/genética , Polimorfismo de Nucleotídeo Único
16.
Adv Healthc Mater ; 13(4): e2302576, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37897434

RESUMO

Intestinal commensal microbiota dysbiosis and immune dysfunction are significant exacerbating factors in inflammatory bowel disease (IBD). To address these problems, Pluronic F-127-coated tungsten diselenide (WSe2 @F127) nanozymes are developed by simple liquid-phase exfoliation. The abundant valence transitions of elemental selenium (Se2- /Se4+ ) and tungsten (W4+ /W6+ ) enable the obtained WSe2 @F127 nanozymes to eliminate reactive oxygen/nitrogen species. In addition, the released tungsten ions are capable of inhibiting the proliferation of Escherichia coli. In a model of dextran sodium sulfate-induced colitis, WSe2 @F127 nanozymes modulate the gut microbiota by increasing the abundance of bacteria S24-7 and significantly reducing the abundance of Enterobacteriaceae. Moreover, WSe2 @F127 nanozymes inhibit T-cell differentiation and improve intestinal immune barrier function in a model of Crohn's disease. The WSe2 @F127 nanozymes effectively alleviate IBD by reducing oxidative stress damage, modulating intestinal microbial populations, and remodeling the immune barrier.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Polietilenos , Polipropilenos , Animais , Camundongos , Tungstênio/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/microbiologia , Escherichia coli , Espécies Reativas de Oxigênio , Diferenciação Celular , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
17.
J Hazard Mater ; 465: 133379, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38160555

RESUMO

Ground-level ozone (O3) is a primary air pollutant with potential adverse impacts on human health and ecosystems. Aiming to detect O3 concentration and develop efficient O3 sensing materials, sensing behavior of heterogenous cation (Fe3+, Sn4+ and Sb5+) doped In2O3 nanostructures was investigated. The incorporation of these cations modulated the electronic structure of semiconductor oxides, affecting the density of chemisorbed oxygen species and reactive sites. From O3 sensing results, Fe3+ doped In2O3 based sensors featuring saturated resistance curves in O3 gas, demonstrated fast sensing speed and qualified detection threshold (20 ppb). In contrast, Sn4+ and Sb5+ doped counterparts exhibited non-saturated sensing curves, resulting in slower response/recovery speed. As a proof-of-concept, these optimized sensors were integrated as the sensor array. Coupled to the image recognition technique, this sensor array could successfully discriminate O3 and NOx. That is, through the tailored combination of material modulation and sensor array, this study paves a novel approach for highly sensitive and selective O3 detection.

18.
Front Med (Lausanne) ; 10: 1270368, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38076255

RESUMO

Background: Inflammation is the core of Chronic obstructive pulmonary disease (COPD) development. The systemic immune-inflammation index (SII) is a new biomarker of inflammation. However, it is currently unclear what impact SII has on COPD. This study aims to explore the relationship between SII and COPD. Methods: This study analyzed patients with COPD aged ≥40 years from the National Health and Nutrition Examination Survey (NHANES) in the United States from 2013 to 2020. Restricted Cubic Spline (RCS) models were employed to investigate the association between Systemic immune-inflammation index (SII) and other inflammatory markers with COPD, including Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR). Additionally, a multivariable weighted logistic regression model was utilized to assess the relationship between SII, NLR and PLR with COPD. To assess the predictive values of SII, NLR, and PLR for COPD prevalence, receiver operating characteristic (ROC) curve analysis was conducted. The area under the ROC curve (AUC) was used to represent their predictive values. Results: A total of 10,364 participants were included in the cross-sectional analysis, of whom 863 were diagnosed with COPD. RCS models observed non-linear relationships between SII, NLR, and PLR levels with COPD risk. As covariates were systematically adjusted, it was found that only SII, whether treated as a continuous variable or a categorical variable, consistently remained positively associated with COPD risk. Additionally, SII (AUC = 0.589) slightly outperformed NLR (AUC = 0.581) and PLR (AUC = 0.539) in predicting COPD prevalence. Subgroup analyses revealed that the association between SII and COPD risk was stable, with no evidence of interaction. Conclusion: SII, as a novel inflammatory biomarker, can be utilized to predict the risk of COPD among adults aged 40 and above in the United States, and it demonstrates superiority compared to NLR and PLR. Furthermore, a non-linear association exists between SII and the increased risk of COPD.

19.
Front Public Health ; 11: 1276326, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38155897

RESUMO

Background: The association between dietary patterns and depression has gained significant attention, but the relationship between fruit intake and depression remains unclear. This study aimed to investigate the role of fruit intake in the risk of depression using data from the National Health and Nutrition Examination Survey (NHANES) and Mendelian randomization (MR) analysis, and further explore the causal relationship between them. Materials and methods: Cross-sectional analysis was conducted using the 2005-2018 NHANES data. Specialized weighted complex survey design analysis software was used for multivariate logistic analysis. Additionally, genetic variants for fruit intake and depression, as well as its related neuroticism traits, from the GWAS were used as instrumental variables in MR analysis. The inverse variance weighted (IVW) method was employed as the primary analysis method to evaluate the causal relationship between them. MR-Egger regression, MR-PRESSO test, and leave-one-out analysis were conducted to assess heterogeneity and pleiotropy. Results: In NHANES, compared to the lowest quartile (Q1, <0.12 cup], the highest quartile (Q4, >1.49 cups) of fruit intake showed a significant reduction in the risk of depression after adjusting for relevant covariates. Model 3, after rigorous adjustment for multiple covariates, demonstrated improved predictive performance in both Receiver operating characteristic (ROC) curve and Decision curve analysis (DCA). In Model 3, the proportion of reduced depression risk associated with fruit intake reached 31% (OR = 0.69, 95% CI: 0.50-0.95). This association remained significant in the MR analysis (OR = 0.92, 95% CI = 0.87-0.96; p = 5.09E-04). Fruit intake was also associated with a decreased risk of neuroticism traits related to depression, including feeling lonely (OR = 0.82, 95% CI = 0.74-0.90; p = 2.91E-05), feeling miserable (OR = 0.79, 95% CI = 0.72-0.87; p = 2.35E-06), feeling fed-up (OR = 0.75, 95% CI = 0.68-0.83; p = 2.78E-08), irritable mood (OR = 0.89, 95% CI = 0.79-0.99; p = 0.03), and neuroticism (OR = 0.85, 95% CI = 0.76-0.96; p = 9.94E-03). The causal relationship between feeling lonely and fruit intake was bidirectional. Conclusion: Increased fruit intake has a causal effect in reducing the risk of depression and is beneficial for related psychological well-being.


Assuntos
Depressão , Análise da Randomização Mendeliana , Estudos Transversais , Frutas , Inquéritos Nutricionais
20.
BMC Public Health ; 23(1): 2335, 2023 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-38001456

RESUMO

BACKGROUND: The association between exposure to environmental metals and chronic obstructive pulmonary disease (COPD) is preventing chronic lung diseases. However, little is currently known about the interaction between heavy metals and flavonoids in relation to the risk of COPD. This study aims to bridge this knowledge gap by leveraging The National Health and Nutrition Examination Survey (NHANES) database to evaluate thecorrelation between blood levels of heavy metals (cadmium, lead, mercury) and the intake of various flavonoid compounds (isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, flavonols, total flavonoids). Additionally, appropriate dietary recommendations are provided based on the study findings. MATERIALS AND METHODS: Cross-sectional analysis was conducted using the 2007-2010 and 2017-2018 NHANES data. Specialized weighted complex survey design analysis software was used for data analysis. Multivariate logistic regression models and restricted cubic splines (RCS) were used to evaluate the relationship between blood heavy metal levels, flavonoids intake, and COPD incidence in all participants, and to explore the effect of different levels of flavonoids intake on COPD caused by heavy metal exposure. RESULTS: A total of 7,265 adults aged ≥ 40 years were analyzed. Higher levels of blood cadmium (Cd), blood lead and Anthocyanidin (AC) intake were independently associated with an increased risk of COPD (Cd highest quantile vs. lowest: OR = 1.73, 95% CI, 1.25-2.3; Lead highest quantile vs. lowest quantile: OR = 1.44, 95% CI, 1.11-1.86; AC highest quantile vs. lowest: OR = 0.73, 95% CI, 0.54-0.99). When AC intake exceeded 11.56 mg/d, the effect of Cd exposure on COPD incidence decreased by 27%, and this finding was more significant in smokers. CONCLUSION: Higher levels of Cd (≥ 0.45ug/L) and lead (≥ 0.172 ug/L) were positively correlated with the risk of COPD among participants aged 40 years and above, while AC intake (≥ 11.56 mg/d) could reduce the risk related to blood Cd.


Assuntos
Metais Pesados , Doença Pulmonar Obstrutiva Crônica , Adulto , Humanos , Flavonoides , Inquéritos Nutricionais , Cádmio , Estudos Transversais , Doença Pulmonar Obstrutiva Crônica/epidemiologia
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