Therapeutic application of circular RNA aptamers in a mouse model of psoriasis.

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.

Causal effects of neuroticism on postpartum depression: a bidirectional mendelian randomization study.

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.

Inorganic carbon limitation decreases ammonium removal and N2O production in the algae-nitrifying bacteria symbiosis system.

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.

Association between high-density lipoprotein cholesterol and type 2 diabetes mellitus: dual evidence from NHANES database and Mendelian randomization analysis.

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.

Warming enhances the negative effects of shrub removal on phosphorus mineralization potential.

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.

Developing antibiotics-based strategies to efficiently enrich ammonia-oxidizing archaea from wastewater treatment plants.

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).

Favipiravir biotransformation by a side-stream partial nitritation sludge: Transformation mechanisms, pathways and toxicity evaluation.

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.

Establishing an efficient membrane bioreactor for simultaneous pollutant removal and purple bacteria production under salinity stress.

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.

Modeling Free Nitrous Acid Inhibition on the Removal of Nitrogen and Atenolol during Sidestream Partial Nitritation Processes.

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.

A high-fidelity, dual site-specific integration system in CHO cells by a Bxb1 recombinase.

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.

2D Nanozymes Modulate Gut Microbiota and T-Cell Differentiation for Inflammatory Bowel Disease Management.

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.

Effect of heterogenous dopant and high temperature pulse excitation on ozone sensing behavior of In2O3 nanostructures and an image recognition method coupled to ozone sensing array.

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.

The association between systemic immune-inflammation index and chronic obstructive pulmonary disease in adults aged 40 years and above in the United States: a cross-sectional study based on the NHANES 2013-2020.

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.

Increased fruit intake is associated with reduced risk of depression: evidence from cross-sectional and Mendelian randomization analyses.

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.

Associations of adverse childhood experiences with common psychiatric disorder in later life: results from the China mental health survey.

BACKGROUND: Associations between adverse childhood experiences (ACEs) and common psychiatric disorders among older Chinese individuals have not been well reported. The objectives of this study are to examine the prevalence of ACEs and the associations of ACEs with common psychiatric disorders among older adults in China. METHODS: The study used data from the China Mental Health Survey (CMHS), a nationally representative epidemiological survey, which used computer-assisted personal interviewing (CAPI), logistic regression models were used to examine community-based adult psychiatric disorders and associated risk factors. Finally, 2,317 individuals aged 60 years or over were included in the CMHS. The national prevalence of ACEs in older adults were estimated and logistic regression were used to analyse the association between ACEs and past-year psychiatric disorders. RESULTS: Prevalence of ACEs among older adults in China was 18.1%. The three most common types of ACEs were neglect (11.6%), domestic violence (9.2%), and parental loss (9.1%). This study proved the association between ACEs and common past-year psychiatric disorders in older adults. ACEs increased the risk of past-year psychiatric disorders in older adults. After adjustment for age, sex, marital status, employment status, education, rural or urban residence, region, and physical diseases, the association between ACEs and past-year psychiatric disorders were still significant. CONCLUSIONS: ACEs are linked to an increased risk for past-year psychiatric disorders in older adults. ACEs may have long-term effects on older adults' mental well-being. Preventing ACEs may help reduce possible adverse health outcomes in later life.

Heavy metal levels and flavonoid intakes are associated with chronic obstructive pulmonary disease: an NHANES analysis (2007-2010 to 2017-2018).

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.

Association between genetically proxied lipid-lowering drug targets, lipid traits, and amyotrophic lateral sclerosis: a mendelian randomization study.

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.

Model-based assessment of mainstream nitrate/nitrite-dependent anaerobic methane oxidation and Anammox process in granular sludge at low temperature.

The process of nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) coupled with anaerobic ammonium oxidation (Anammox) is one of groundbreaking discoveries for nitrogen removal and methane emission reduction from wastewater simultaneously. Yet its treatment of mainstream wastewater at low temperature is still a major challenge. In this work, a one-dimensional granular sludge model incorporating Arrhenius conversion for temperature effects was constructed to depict the relationships among n-DAMO microorganisms and Anammox. The model framework was successfully evaluated with 380 days measurement data from a membrane granular sludge reactor (MGSR) operated at temperature of 20-10 °C and fed with ammonium and nitrite. The model could satisfactorily predict the kinetics of nitrogen removal rates, effluent nitrogen concentrations and biomass fractions in MGSR at varying temperatures. Despite the decrease in microbial activity of functional microorganisms, the coupled n-DAMO and Anammox process based on granule system in mainstream wastewater treatment achieved a TN removal efficiency of about 98 % and a stable nitrogen removal rate of 0.55 g L-1 d-1. The model developed is expected to facilitate fundamentally understanding the underlying mechanisms of the coupled process and provide proposals for its practical engineering application in wastewater treatment plants.

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OBJECTIVES: To investigate the association between childhood trauma and game addiction in adolescents, as well as the mediating effect of self-control. METHODS: A cross-sectional study was conducted using cluster random sampling. The participants were 2 664 adolescents from a senior high school in Henan Province. The research tools included a demographic data questionnaire, Childhood Trauma Questionnaire-Short Form, Self-Control Scale, and Game Addiction Scale for Adolescents. The Bootstrap method was used to test the parallel mediating effect, with the five dimensions of self-control as mediators. RESULTS: The prevalence of game addiction among the adolescents was 17.68% (471/2 664). There was a positive correlation between childhood trauma and game addiction scores (P<0.01), and a negative correlation between childhood trauma scores and each dimension of self-control (P<0.01). Moreover, all five dimensions of self-control were negatively correlated with game addiction scores (P<0.01) and acted as parallel mediators between childhood trauma and game addiction. The mediating effects of restraint from entertainment (accounting for 15.6% of the total effect) and resistance to temptation (accounting for 10.6% of the total effect) were stronger. CONCLUSIONS: Childhood trauma may increase the risk of game addiction by impairing adolescents' self-control abilities. The reduction of childhood trauma can cultivate self-control in adolescents and prevent the occurrence of game addiction.

Association between genetically proxied HMGCR inhibition and male reproductive health: A Mendelian randomization study.

BACKGROUND: The causal associations between statin use and male sex hormone levels and related disorders have not been fully understood. In this study, we employed Mendelian randomization for the first time to investigate these associations. METHODS: In two-sample Mendelian randomization framework, genetic proxies for hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibition were identified as variants in the HMGCR gene that were associated with both levels of gene expression and low density lipoprotein cholesterol (LDL-C). We assessed the causal relationship between HMGCR inhibitor and 5 sex hormone levels/2 male-related diseases. Additionally, we investigated the association between 4 circulating lipid traits and outcomes. The "inverse variance weighting" method was used as the primary approach, and we assessed for potential heterogeneity and pleiotropy. In a secondary analysis, we revalidated the impact of HMGCR on 7 major outcomes using the summary-data-based Mendelian randomization method. RESULTS: Our study found a significant causal association between genetic proxies for HMGCR inhibitor and decreased levels of total testosterone (TT) (LDL-C per standard deviation = 38.7mg/dL, effect = -0.20, 95% confidence interval [CI] = -0.25 to -0.15) and bioavailable testosterone (BT) (effect = -0.15, 95% CI = -0.21 to -0.10). Obesity-related factors were found to mediate this association. Furthermore, the inhibitor were found to mediate a reduced risk of prostate cancer (odds ratio = 0.81, 95%CI = 0.7-0.93) by lowering bioavailable testosterone levels, without increasing the risk of erectile dysfunction (P = .17). On the other hand, there was a causal association between increased levels of LDL-C, total cholesterol, triglycerides (TG) and decreased levels of TT, sex hormone-binding globulin, and estradiol. CONCLUSIONS: The use of HMGCR inhibitor will reduce testosterone levels and the risk of prostate cancer without the side effect of erectile dysfunction. LDL-C, total cholesterol, and TG levels were protective factors for TT, sex hormone-binding globulin, and estradiol.