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Transition metal catalysts (TMCs) mediated bioorthogonal catalysis expand the chemical possibilities within cells. Developing synthetic TMCs tools that emulate the efficiency and specificity of natural metalloenzymes is a rewarding yet challenging endeavor. Here, we highlight the potential of molecularly imprinted enzyme mimics (MIEs) containing a Cu center and specific substrate binding domain, for conducing dimethylpropargyloxycarbonyl (DmProc) cleavage reactions within cells. Our studies reveal that the Cu‐MIEs act as highly specific guides, precisely catalyzing target substrates, even in glutathione (GSH)‐rich cellular environments. By adapting templates similar to the target substrates, we evolved Cu‐MIEs activity to a high level and provided a method to broaden its scope to other unique substrates. This system was applied to a thyroid hormone (T3)‐responsive gene switch model, inducing firefly luciferase expression by T3 in cells. This approach verifies that MIEs effectively rescue DmProc‐bearing T3 prodrugs and seamlessly integrating themself into cellular biocatalytic networks. [ABSTRACT FROM AUTHOR]

Background Methods Results Interpretation Previous studies have observed liver abnormalities in amyotrophic lateral sclerosis (ALS) patients. This study aimed to investigate whether early signs of liver disease, measured by magnetic resonance imaging‐derived iron‐corrected T1‐mapping (cT1), are risk factors for developing ALS.cT1 and proton density fat fraction were measured and automatically analyzed using LiverMultiScan® software. The Fibrosis‐4 index was calculated using an established formula based on age and blood markers. Cox proportional hazard models were used to examine the relationship between liver disease, liver biomarkers, and incident ALS.In a cohort of 533,707 individuals from UK Biobank, 24 ALS cases were identified among 28,328 participants with liver disease during the follow‐up period. Among a total of 33,959 individuals with complete liver imaging data, 15 incident ALS cases were observed during a median follow‐up period of 5.6 years. Individuals with liver disease had a higher risk of developing ALS, with an adjusted hazard ratio of 7.35 (95% CI 4.47–12.09; p < 0.001). An increase in cT1 was also associated with a higher risk of ALS. After adjusting for age, sex, Townsend deprivation index, smoking status, alcohol intake frequency, body mass index, proton density fat fraction, Fibrosis‐4, and metabolic syndrome, an increase in cT1 remained significantly associated with a higher risk of ALS, with an adjusted hazard ratio of 3.15 (95% CI 1.79–5.55) per 1‐SD increase. Sensitivity analyses confirmed these robust results.Liver disease activity, indicated by cT1, increases the risk of developing ALS, independent of metabolic syndrome, liver fat, or fibrosis. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Objective: Although metabolic abnormalities are implicated in the etiology of neurodegenerative diseases, their role in the development of amyotrophic lateral sclerosis (ALS) remains a subject of controversy. We aimed to identify the association between metabolic syndrome (MetS) and the risk of ALS. Methods: This study included 395,987 participants from the UK Biobank to investigate the relationship between MetS and ALS. Cox regression model was used to estimate hazard ratios (HR). Stratified analyses were performed based on gender, body mass index (BMI), smoking status, and education level. Mediation analysis was conducted to explore potential mechanisms. Results: In this study, a total of 539 cases of ALS were recorded after a median follow‐up of 13.7 years. Patients with MetS (defined harmonized) had a higher risk of developing ALS after adjusting for confounding factors (HR: 1.50, 95% CI: 1.19–1.89). Specifically, hypertension and high triglycerides were linked to a higher risk of ALS (HR: 1.53, 95% CI: 1.19–1.95; HR: 1.31, 95% CI: 1.06–1.61, respectively). Moreover, the quantity of metabolic abnormalities showed significant results. Stratified analysis revealed that these associations are particularly significant in individuals with a BMI <25. These findings remained stable after sensitivity analysis. Notably, mediation analysis identified potential metabolites and metabolomic mediators, including alkaline phosphatase, cystatin C, γ‐glutamyl transferase, saturated fatty acids to total fatty acids percentage, and omega‐6 fatty acids to omega‐3 fatty acids ratio. Interpretation: MetS exhibits a robust association with an increased susceptibility to ALS, particularly in individuals with a lower BMI. Furthermore, metabolites and metabolomics, as potential mediators, provide invaluable insights into the intricate biological mechanisms. ANN NEUROL 2024;96:788–801 [ABSTRACT FROM AUTHOR]

Manganese dioxide (MnO2) nanosheets with a well-defined 2D structure can serve as catalase (CAT) and superoxide dismutase (SOD) mimics and hold a high potential in regulating the oxidative stress of atopic dermatitis (AD). However, facile, time-saving, and scalable synthesis of high-activity MnO2 nanosheets is still challenging. Here, we report a one-step oxidative synthesis strategy of MnO2 nanosheets and explore its potential as CAT and SOD mimics to exert antioxidant functions. After further gelatinization by integrating MnO2 nanosheets into a poly-(ethylene glycol)-diacrylate (PEGDA) polymer (PGM hydrogel), the obtained PGM hydrogel, characterized by well-designed cross-linking density and moisture retention, retains high antioxidation and cytoprotection ability. In AD-bearing mouse models, the PGM hydrogel facilitates the recovery of the impaired mice skin, reducing the severity score, scratching numbers, epidermal thickness, and immune factors, including mast cells, IgE antibodies, and inflammatory cytokines IL-4 and IL-10. Such a simple and reliable approach paves the way for the scale synthesis of MnO2 nanosheets and its practical application as antioxidative and immunoregulation agents for AD therapy. [ABSTRACT FROM AUTHOR]

Nowadays, since the most of individual investors provide money to company for real cash inflows, paying cash dividend, as the main way to pay money back to the investors, is definitely paid more attention to. But for the company, keeping money in itself can help to grab development opportunities in time. This essay reveals the possible outcomes in dividend policy because of the ultimate controller’s changing. Given to the results of existing research works and the data from Chinese listed companies, after exemplifying some typical cases, the conclusion can be illustrated clearly: The ultimate controller’s changing effect cash dividend payment by generating disputes of share transfer, complicating the pyramid-shaped shareholding structure, and damaging corporate governance and operating ability. Further more, auditing and cash dividend payment are substitutes for each other as corporate economic supervision tools. Meanwhile, auditing can reduce the negative influence of ultimate controller’s changing so that investors can get more cash dividend. This paper offers a new perspective for studies about the factors of cash dividend tendency and briefly discusses how the heated topic of auditing exerts influence on the relationship.

A tumor microenvironment is distinct from normal tissue cells in characteristic physiochemical conditions, based on which we can design tumor-specific therapy modalities. Herein, we introduce a concept of multimodal therapies, which integrates the characteristics of each therapy modality for efficient tumor therapy: tumor starvation-triggered synergism with enhanced chemodynamic therapy and activated chemotherapy. Fe3O4 nanoparticles (Fenton reaction catalysts) and a hypoxic prodrug tirapazamine (TPZ) were loaded in mesoporous silica nanoparticles (MSN) and GOX was grafted onto its surface, which was designed and fabricated for sequential multimodal therapies. Logically, glucose oxidase (GOX) deprived tumor cells of nutrients (glucose and oxygen) for starvation therapy and tumorous abnormality amplifications (elevated acidity, exacerbated hypoxia, and increased H2O2) were amplified by the GOX-driven oxidation reaction simultaneously. Specifically, elevated acidity could accelerate the release of iron ions and enhanced Fenton reaction efficiency. Associated with increased H2O2, an elevated ROS level was detected, which enhanced the chemodynamic therapy. Exacerbated hypoxia activated the hypoxic prodrug TPZ for tumor-specific chemotherapy programmatically. Particularly, via integrating starvation therapy, enhanced chemodynamic therapy, and activated chemotherapy, the sequential multimodal therapies were specifically designed for the tumor microenvironment and achieved effective abnormality amplifications and high therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Transition metal catalysts (TMCs) mediated bioorthogonal catalysis expand the chemical possibilities within cells. Developing synthetic TMCs tools that emulate the efficiency and specificity of natural metalloenzymes is a rewarding yet challenging endeavor. Here, we highlight the potential of molecularly imprinted enzyme mimics (MIEs) containing a Cu center and specific substrate binding domain, for conducing dimethylpropargyloxycarbonyl (DmProc) cleavage reactions within cells. Our studies reveal that the Cu-MIEs act as highly specific guides, precisely catalyzing target substrates, even in glutathione (GSH)-rich cellular environments. By adapting templates similar to the target substrates, we evolved Cu-MIEs activity to a high level and provided a method to broaden its scope to other unique substrates. This system was applied to a thyroid hormone (T3)-responsive gene switch model, inducing firefly luciferase expression by T3 in cells. This approach verifies that MIEs effectively rescue DmProc-bearing T3 prodrugs and seamlessly integrating themself into cellular biocatalytic networks., (© 2024 Wiley-VCH GmbH.)

Background: Diet habit is associated with mental health which has been suggested to be an independent risk factor. Nevertheless, evidence concerning the association between beverage consumption and age-specific mental health remains limited. Here we estimate the association between six types of beverages and depression and anxiety disorders., Methods: We included 188,355 participants who completed at least one dietary questionnaire and were free of depression and anxiety disorders at baseline from the UK-Biobank. Cox proportional hazard models and substituting analyses were used., Results: (i) During an average of 11.15 years of follow-up, 5884(3.12 %) participants with incident depression and 6445(3.42 %) anxiety disorders were documented. (ii)In individuals aged <60 years, the consumption of SSBs (sugar-sweetened beverages) and ASBs (artificially-sweetened beverages) (>1 serving/day) was associated with higher hazard of depression disorders (SSBs: HR 1.14, 95 % CI 1.02-1.28; ASBs: HR 1.23, 95 % CI 1.09-1.38); whereas, intakes of pure fruit/vegetable juices (PiSs) and coffee were associated with lower hazard of depression disorders(PiSs: HR 0.81, 95 % CI 0.72-0.92; coffee: HR 0.88, 95 % CI 0.81-0.96). (iii)In individuals aged ≥60 years, higher intakes of PiSs and coffee were related to lower hazard of depression and anxiety disorders. (iv)Replacing PiSs or coffee with SSBs was significantly associated with reduced depression and anxiety disorders in individuals aged <60 years while replacing PiSs or coffee with milk was consistently correlated with lower depression and anxiety disorders in those aged over 60 years., Conclusion: Individual beverages showed divergent associations with depression and anxiety disorders at different age levels, which underscores the potential relationship of prudent beverage choices in mitigating the risk of mental health., Competing Interests: Declaration of competing interest The authors have stated explicitly that there are no conflicts of interest in connection with this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)