The relationship between coffee-related factors and cortical and hippocampal structure: a triangulation of evidence approach and Mendelian randomization research

ObjectiveExisting studies have reported sustained changes in the cortical structure of rats due to coffee-related factors, which are speculated to occur in the human body. However, there is a lack of research on this topic. Additionally, previous observational studies have found the impact of diseases on cortical structure and the potential therapeutic effects of coffee on these diseases. Our aim was to study the causal effects of coffee-related factors on the human brain using SNPs (single nucleotide polymorphisms). We will connect these discovered causal effects to the impact of diseases on the brain. Through triangulating evidence, we will reveal the potential active areas of coffee in preventing diseases.MethodsWe utilized GWAS data from multiple cohorts and their databases, selecting instrumental variables for genetic prediction of coffee intake and plasma levels of caffeine and its direct metabolites. We applied these instrumental variables to individual data on cortical thickness and surface area, as well as hippocampal volume, from the ENIGMA and CHARGE consortium for Mendelian randomization analysis (MR). Triangular evidence was obtained by integrating existing evidence through a specified retrieval strategy, calculating the overlap between coffee's effects on brain regions and disease-related brain regions to identify potential regions of action.ResultsThe MR analysis yielded 93 positive results for 9 exposures, among which theobromine, a metabolite in the caffeine pathway, was found to be associated with increased hippocampal volume. For cortical structure, theobromine in the caffeine pathway was associated with a decrease in total surface area, while theobromine and caffeine in the pathway were associated with an increase in total thickness. The overlap rate of triangular evidence showed no difference in both overall and subgroup analyses, indicating a high overlap between the effects of coffee on brain regions and disease.ConclusionsFrom predicted outcomes from causal effects, coffee intake-related factors may have lasting effects on cortical structure. Additionally, theobromine and theophylline have the greatest impact on certain brain gyri, rather than caffeine. Triangulation evidence indicates that disease and coffee intake-related factors act on the same cortical regions, suggesting the presence of potential shared or antagonistic pathways

Flexibility-enhanced strategies of generations to improve the integration of renewable energy considering uncertainties

Power systems with a high proportion of renewable energy are confronted with immense challenges and a huge amount of renewable energy has been curtailed. To promote the integration of renewable energy, this paper focus on exploiting the generation flexibilities. For hydropower units, a high-resolution dynamic regulation model of reservoir volume is proposed, in which the real-time situation of inflow is considered. The reservoir’s flexibility which is hindered by the static flood water limit level (FLWL) is exploited by this method. For thermal units, a deep peak regulation of thermal is constructed to enhance the system’s flexibility. Furthermore, considering the uncertainties of renewable energy, a chance-constrained reservoir flexible model influenced by random reservoir inflow and a chance-constrained spinning reserve and power flow model influenced by the wind uncertainty are developed. Based on those models and their coordination, an optimal dispatching model considering generation flexibilities and uncertainties is proposed. Simulation results on the IEEE 30-bus system show that the proposed model with multiple flexible resources can increase wind power penetration by 10% and save half of the cost compared with the conventional dispatching methods. These results demonstrated the efficiency of the proposed method whether the integration of renewable energy or the saving of operation costs

Reduce operational costs of thermal power units in power systems using the flexibility of district cooling systems

The high volatility of wind generation causes the thermal power units to start up and shut down frequently because there is a lack of flexibility in the power systems, which poses a challenge to economic operation. With the increase in cooling demand, district cooling systems (DCSs) have received attention in recent years and have been built in many regions, which offer a novel option to alleviate the above problems by utilizing the complementarity between power and cooling systems. In a typical DCS, the cooling source is a key component that generates cooling energy for the entire cooling system. Utilization of the cooling storage capacity of cooling sources in DCSs is an economical and efficient measure for more operational flexibility of power systems. Therefore, this paper proposes a unit commitment model with combined power systems and DCSs to reduce the operational costs of thermal power units and wind curtailment. In this model, an accurate model of a cooling source with an ice storage tank, where the cooling characteristics and energy transmission process are reflected, is built to fully excavate the flexibility potential of DCSs. Finally, numerical simulations are performed to show that the proposed method reduces the operational costs by 15.78% within a scheduling day and makes the wind curtailment close to zero. The results of the above comparison demonstrate that the method can improve the operational economy and encourage wind power integration while assuring an adequate supply of electricity and cooling

The alleviated symptoms in ovalbumin‐allergic mice treated with selenium‐enriched tea polysaccharide by modulation of intestinal flora and gut metabolites

Abstract Ovalbumin (OVA) in egg is one of the predominant causes of food allergy around the world. In the present study, the alleviating effect of selenium‐enriched tea polysaccharide (Se‐TPS) on OVA allergy was evaluated, and the underlying mechanistic insights were investigated. Se‐TPS significantly alleviated the clinical manifestations and diarrhea of allergic mice, accelerated the recovery of jejunal injury, and decreased the immune organ index. Meanwhile, Se‐TPS decreased the levels of immunoglobulin E (IgE), histamine, and IL‐4 in serum, increased the levels of IFN‐γ, and promoted the balance of Th1/Th2 cells. Furthermore, the intervention of Se‐TPS reshaped the gut microbiota structure of OVA‐allergic mice. Se‐TPS increased the abundance of Lachnospiraceae_NK4A136_group, unclassified_f_Lachnospiraceae, and Alistipes, whereas decreased the Faecalibaculum abundance. Analysis of intestinal metabolites showed that Se‐TPS treatment caused a significant increase in homocitrulline and 7a‐hydroxyandrost‐4‐ene‐3,17‐dione levels. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment results indicated that Se‐TPS treatment may alleviate allergic symptoms by enhancing the anti‐inflammatory ability of OVA‐allergic mice through neuroimmunity

Polymorphisms of Leptin-b Gene Associated with Growth Traits in Orange-Spotted Grouper (Epinephelus coioides)

In mammals, leptin has been demonstrated to perform important roles in many physiological activities and to influence development, growth, metabolism and reproduction. However, in fish, its function is still unclear. Duplicate leptin genes, leptin-a and leptin-b, have been identified in the orange-spotted grouper. In the present study, the polymorphisms in the leptin-b gene of the orange-spotted grouper were detected, and the relation between these polymorphisms and 12 growth traits were analyzed. Six polymorphisms (including 3 single nucleotide polymorphisms (c.14G>A, c.93A>G, c.149G>A) in exon 1, 2 SNPs (c.181A>G, c.193G>A) in intron 1, and 1 SNP (c.360C>T) in exon 2) were identified and genotyped from 200 different individuals. The results revealed that the SNP c.149G>A was significantly associated with growth traits, that the heterozygous mutation genotype GA having negative effects on growth traits. However, the other five SNPs (c.14G>A, c.93A>G, c.181A>G, c.193G>A, c.360C>T) did not show significant associations with all the growth traits. Compared with our findings in leptin-a gene, the results suggested that the leptin-a hormone has more important physiological effects in fish bodies than the leptin-b type. Moreover, leptin genes were supposed to be one class of major candidate genes of regulating growth traits in the orange-spotted grouper

High-Fidelity Sensitive Tracing Circulating Tumor Cell Telomerase Activity

Dynamic tracing of intracellular telomerase activity plays a crucial role in cancer cell recognition and correspondingly in earlier cancer diagnosis and personalized precision therapy. However, due to the complexity of the required reaction system and insufficient loading of reaction components into cells, achieving a high-fidelity determination of telomerase activity is still a challenge. Herein, an Aptamer-Liposome mediated Telomerase activated poly-Molecular beacon Arborescent Nanoassembly(ALTMAN) approach was described for direct high-fidelity visualization of telomerase activity. Briefly, intracellular telomerase activates molecular beacons, causing their hairpin structures to unfold and produce fluorescent signals. Furthermore, multiple molecular beacons can self-assemble, forming arborescent nanostructures and leading to exponential amplification of fluorescent signals. Integrating the enzyme-free isothermal signal amplification successfully increased the sensitivity and reduced interference by leveraging the skillful design of the molecular beacon and the extension of the telomerase-activated TTAGGG repeat sequence. The proposed approach enabled ultrasensitive visualization of activated telomerase exclusively with a prominent detection limit of 2 cells·μL–1 and realized real-time imaging of telomerase activity in living cancer cells including blood samples from breast cancer patients and urine samples from bladder cancer patients. This approach opens an avenue for establishing a telomerase activity determination and in situ monitoring technique that can facilitate both telomerase fundamental biological studies and cancer diagnostics

Multi-omics and single cell characterization of cancer immunosenescence landscape

Abstract Cellular senescence (CS) is closely related to tumor progression. However, the studies about CS genes across human cancers have not explored the relationship between cancer senescence signature and telomere length. Additionally, single-cell analyses have not revealed the evolutionary trends of malignant cells and immune cells at the CS level. We defined a CS-associated signature, called “senescence signature”, and found that patients with higher senescence signature had worse prognosis. Higher senescence signature was related to older age, higher genomic instability, longer telomeres, increased lymphocytic infiltration, higher pro-tumor immune infiltrates (Treg cells and MDSCs), and could predict responses to immune checkpoint inhibitor therapy. Single-cell analysis further reveals malignant cells and immune cells share a consistent evolutionary trend at the CS level. MAPK signaling pathway and apoptotic processes may play a key role in CS, and senescence signature may effectively predict sensitivity of MEK1/2 inhibitors, ERK1/2 inhibitors and BCL-2 family inhibitors. We also developed a new CS prediction model of cancer survival and established a portal website to apply this model ( https://bio-pub.shinyapps.io/cs_nomo/ )