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Background: Delirium significantly contributes to both mortality and morbidity among hospitalized older adults. Furthermore, delirium leads to escalated healthcare expenditures, extended hospital stays, and enduring cognitive deterioration, all of which are acknowledged detrimental outcomes. Nonetheless, the current strategies for predicting and managing delirium remain constrained. Our aim was to employ Mendelian randomization (MR) to investigate the potential causal relationship between metabolites and delirium, as well as to identify potential therapeutic targets., Methods: We identified 129 distinct blood metabolites from three genome-wide association studies (GWASs) conducted on the metabolome, involving a total of 147,827 participants of European descent. Genetic information pertaining to delirium was sourced from the ninth iteration of the Finngen Biobank, encompassing 359,699 individuals of Finnish ancestry. We conducted MR analyses to evaluate the connections between blood metabolites and delirium. Additionally, we extended our analysis to encompass the entire phenome using MR, aiming to uncover potential on-target consequences resulting from metabolite interventions., Results: In our investigation, we discovered three metabolites serving as causal mediators in the context of delirium: clinical low density lipoprotein cholesterol (LDL-C) (odds ratio [OR]: 1.47, 95% confidence interval [CI]: 1.25-1.73, p = 3.92 x 10 -6 ), sphingomyelin (OR: 1.47, 95% CI: 1.25-1.74, p = 5.97 x 10 -6 ), and X-11593-O-methylascorbate (OR: 0.21, 95% CI: 0.10-0.43, p = 1.86 x 10 -5 ). Furthermore, utilizing phenome-wide MR analysis, we discerned that clinical LDL-C, sphingomyelin, and O-methylascorbate not only mediate delirium susceptibility but also impact the risk of diverse ailments., Limitations: (1) Limited representation of the complete blood metabolome, (2) reliance on the PheCode system based on hospital diagnoses may underrepresent conditions with infrequent hospital admissions, and (3) limited to European ancestry., Conclusion: The genetic prediction of heightened O-methylascorbate levels seems to correspond to a diminished risk of delirium, in contrast to the association of elevated clinical LDL-C and sphingomyelin levels with an amplified risk. A comprehensive analysis of side-effect profiles has been undertaken to facilitate the prioritization of drug targets. Notably, O-methylascorbate emerges as a potentially auspicious target for mitigating and treating delirium, offering the advantage of lacking predicted adverse side effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Long, Lin, Zhang, Lin, Yao, Zhang, Li, Liu, Ying, Wang and Hua.)

Heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria are aerobic microorganisms that can remove nitrogen under high-salt conditions, but their performance in practical applications are not satisfactory. As a compatible solute, trehalose helps microorganisms to cope with high salt stress by participating in the regulation of cellular osmotic pressure, and plays an important role in promoting the nitrogen removal efficiency of microbial populations in the high-salt environment. We investigated the mechanism of exogenous-trehalose-enhanced metabolism of HN-AD community under high-salt stress by starting up a membrane aerobic biofilm reactor (MABR) to enrich HN-AD bacteria, and designed a C 150 experimental group with 150 μmol/L trehalose addition and a C 0 control group without trehalose. The reactor performance and the community structure showed that NH 4 + -N, total nitrogen (TN) and chemical oxygen demand (COD) removal efficiency were increased by 29.7%, 28.0% and 29.1%, respectively. The total relative abundance of salt-tolerant HN-AD bacteria (with Acinetobacter and Pseudofulvimonas as the dominant genus) in the C 150 group reached 66.8%, an 18.2% increase compared with that of the C 0 group. This demonstrated that trehalose addition promoted the enrichment of salt-tolerant HN-AD bacteria in the high-salt environment to enhance the nitrogen removal performance of the system. In-depth metabolomics analysis showed that the exogenous trehalose was utilized by microorganisms to improve proline synthesis to increase resistance to high-salt stress. By regulating the activity of cell proliferation signaling pathways (cGMP-PKG, PI3K-Akt), phospholipid metabolism pathway and aminoacyl-tRNA synthesis pathway, the abundances of phosphoethanolamine, which was one of the glycerophospholipid metabolites, and purine and pyrimidine were up-regulated to stimulate bacterial aggregation and cell proliferation to promote the growth of HN-AD bacteria in the high-salt environment. Meanwhile, the addition of trehalose accelerated the tricarboxylic acid (TCA) cycle, which might provide more electron donors and energy to the carbon and nitrogen metabolisms of HN-AD bacteria and promote the nitrogen removal performance of the system. These results may facilitate using HN-AD bacteria in the treatment of high-salt and high-nitrogen wastewater.

Objective: To investigate the significance of NADPH quinine oxidoreductase 1 (NQO1) protein overexpression on prognostic evaluation of head and neck squamous cell carcinoma (HNSCC)., Methods: NQO1 protein was detected in 162 of HNSCC, 45 cases of adjacent nontumor tissues and 26 samples of normal head and neck epithelia using EnVision immunohistochemical. Correlation between NQO1 overexpression and patients prognosis was also analyzed., Results: The positive rate and strongly positive rate of NQO1 protein were 84.0% (136/162) and 69.8% (113/162) in HNSCC, respectively, and both of which were significantly higher than either those in adjacent nontumor tissues and normal head and neck epithelia (both P < 0.01). NQO1 expression was significantly correlated with the clinical stage, pT and chemoradiotherapy of HNSCC (P < 0.01). Kaplan-Meier survival analysis showed that overall survival and disease-free survival rates were significantly higher in HNSCC patients with high level NQO1 expression than that those with low level of NQO1 expression (Log-rank = 6.625 , P = 0.010;Log-rank = 6.234 , P = 0.013). Additional analysis by Cox proportional hazard regression model showed that high level of NQO1 expression was an independent hazard predictor for overall survival of patients with HNSCC (Wald = 6.626, P = 0.008)., Conclusions: NQO1 expression level is closely correlated with the progression and prognosis of patients with HNSCC. High level of NQO1 expression may be used as an important indicator for patients with poor prognostic HNSCC.