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

Objective: Existing 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. Methods: We 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. Results: The 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. Conclusions: From 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.

Light at night exposure and risk of breast cancer: a meta-analysis of observational studies.

Objective: The aim of this meta-analysis is to evaluate the impact of light at night (LAN) exposure on the risk of breast cancer across varying factors. Method: We conducted a systematic search of literature up to July 15, 2023, including PubMed, Cochrane Library, and Embase databases, using keywords related to breast cancer and LAN exposure. Cohort study and case-control study literature on night light exposure and breast cancer risk were included. Statistical analyses were performed using Stata software version 17.0. To address heterogeneity among different studies, we employed a random-effects model for analysis and assessed publication bias using funnel plots and Egger's test. Results: We included 13 case-control and 8 cohort studies with 734,372 participants worldwide. In the Newcastle-Ottawa Scale (NOS) assessments, the average score was 7.43 (ranging from 5 to 9). The overall meta-analysis demonstrated a significant association between exposure to LAN and risk of breast cancer (RR = 1.12; 95% CI: 1.06-1.17; I2 = 31.3%, p < 0.001). In the subgroup analysis, the results of the analysis for study types (case-control studies: RR = 1.16; 95% CI: 1.06-1.27; I2 = 40.4%, p = 0.001; cohort studies: RR = 1.08; 95% CI: 1.04-1.14; I2 = 0.0%, p < 0.001) and the results for light exposure types (outdoor LAN: RR = 1.07; 95% CI: 1.02-1.13; I2 = 30.9%, p = 0.004) are presented. In the analysis conducted for continents, the highest breast cancer risk was observed in the Asian population (Asian: RR = 1.24; 95% CI: 1.15-1.34; I2 = 0.0%, p < 0.001) and in the analysis of estrogen receptor status (ER+: RR = 1.10; 95% CI: 1.03-1.18; I2 = 17.0%, p = 0.005;). We also conducted an analysis on menopausal status and various lifestyles but did not find any statistically significant findings. Conclusion: Our study demonstrates that LAN exposure is associated with an increased risk of breast cancer, particularly in the Asian population. Among the existing hypotheses, the idea that LAN exposure leads to a decrease in melatonin is widely accepted. However, until the mechanism of this effect is clearly elucidated, it is not recommended to take melatonin supplements for breast cancer prevention without medical advice. We hope to conduct more high-quality research, especially concerning the investigation of other environmental confounding factors, to further advance this field.

Improvement of Mechanical Properties of Composites with Surface Modified B4C for Precision Machining.

In order to solve the problem of difficult sintering and high brittleness of B4C-based ceramics, B4C@ZrB2-TiB2 composite powder was synthesized by molten salt method, and B4C-(Zr, Ti)B2 composite ceramics were successfully prepared by spark plasma sintering. The effects of different raw material ratios on the composition, microstructure, and mechanical properties of the prepared composite ceramics were characterized by XRD, XPS, SEM, and TEM. The results show that ZrB2 and TiB2 were grown on the surface of B4C by template mechanism to form a dense nanocrystalline coating, and the original surface of B4C was exposed gradually with the decrease of the ratio of metal powder. When the composite powders were sintered at 1700 °C, ZrB2 and TiB2 formed a solid solution, which can refine grains and improve strength. When the raw material ratio is n(B4C): n(Zr): n(Ti) = 12:1:1, the composite ceramics have excellent comprehensive properties, the Vickers hardness reaches 41.2 GPa.

N-end Rule-Mediated Proteasomal Degradation of ATGL Promotes Lipid Storage.

Cellular lipid storage is regulated by the balance of lipogenesis and lipolysis. The rate-limiting triglyceride hydrolase ATGL (desnutrin/PNPLA2) is critical for lipolysis. The control of ATGL transcription, localization, and activation has been intensively studied, while regulation of the protein stability of ATGL is much less explored. In this study, we showed that the protein stability of ATGL is regulated by the N-end rule in cultured cells and in mice. The N-end rule E3 ligases UBR1 and UBR2 reduce the level of ATGL and affect lipid storage. The N-end rule-resistant ATGL(F2A) mutant, in which the N-terminal phenylalanine (F) of ATGL is substituted by alanine (A), has increased protein stability and enhanced lipolysis activity. ATGLF2A/F2A knock-in mice are protected against high-fat diet (HFD)-induced obesity, hepatic steatosis, and insulin resistance. Hepatic knockdown of Ubr1 attenuates HFD-induced hepatic steatosis by enhancing the ATGL level. Finally, the protein levels of UBR1 and ATGL are negatively correlated in the adipose tissue of obese mice. Our study reveals N-end rule-mediated proteasomal regulation of ATGL, a finding that may potentially be beneficial for treatment of obesity.

Liquid-Phase-Assisted Catalytic Nitridation of Silicon and In Situ Growth of α-Si3N4.

Si3N4 powders were synthesized with Fe, Co, or Ni as catalysts using Si powder at 1250 °C in a nitrogen atmosphere by liquid-phase-assisted catalytic nitridation synthesis (LPA-CNS). The catalytic effects of the metals on the nitridation of silicon powder were investigated by mixing the powder with 2 wt% by mass of Fe, Co, or Ni in a high-temperature liquid phase in flowing nitrogen. The α-Si3N4 micro-morphology could be effectively changed by adjusting the type of catalyst in the initial reaction mixtures. Fe, Co, and Ni promoted the formation of α-Si3N4 at 1250 °C and controlled the morphology of the α-Si3N4 particles. The hexagonal flakes of α-Si3N4 with a better defined morphology were obtained using Ni as the catalyst, compared to that obtained from the other two catalysts.

Ni2P nanocrystals embedded Ni-MOF nanosheets supported on nickel foam as bifunctional electrocatalyst for urea electrolysis.

It's highly desired but challenging to synthesize self-supporting nanohybrid made of conductive nanoparticles with metal organic framework (MOF) materials for the application in the electrochemical field. In this work, we report the preparation of Ni2P embedded Ni-MOF nanosheets supported on nickel foam through partial phosphidation (Ni2P@Ni-MOF/NF). The self-supporting Ni2P@Ni-MOF/NF was directly tested as electrode for urea electrolysis. When served as anode for urea oxidation reaction (UOR), it only demands 1.41 V (vs RHE) to deliver a current of 100 mA cm-2. And the overpotential of Ni2P@Ni-MOF/NF to reach 10 mA cm-2 for hydrogen evolution reaction HER was only 66 mV, remarkably lower than Ni2P/NF (133 mV). The exceptional electrochemical performance was attributed to the unique structure of Ni2P@Ni-MOF and the well exposed surface of Ni2P. Furthermore, the Ni2P@Ni-MOF/NF demonstrated outstanding longevity for both HER and UOR. The electrolyzer constructed with Ni2P@Ni-MOF/NF as bifunctional electrode can attain a current density of 100 mA cm-2 at a cell voltage as low as 1.65 V. Our work provides new insights for prepare MOF based nanohydrid for electrochemical application.

Enhancing fatty acid oxidation negatively regulates PPARs signaling in the heart.

High fatty acid oxidation (FAO) is associated with lipotoxicity, but whether it causes lipotoxic cardiomyopathy remains controversial. Molecular mechanisms that may be responsible for FAO-induced lipotoxic cardiomyopathy are also elusive. In this study, increasing FAO by genetic deletion of acetyl-CoA carboxylase 2 (ACC2) did not induce cardiac dysfunction after 16 weeks of high fat diet (HFD) feeding. This suggests that increasing FAO, per se, does not cause metabolic cardiomyopathy in obese mice. We compared transcriptomes of control and ACC2 deficient mouse hearts under chow- or HFD-fed conditions. ACC2 deletion had a significant impact on the global transcriptome including downregulation of the peroxisome proliferator-activated receptors (PPARs) signaling and fatty acid degradation pathways. Increasing fatty acids by HFD feeding normalized expression of fatty acid degradation genes in ACC2 deficient mouse hearts to the same level as the control mice. In contrast, cardiac transcriptome analysis of the lipotoxic mouse model (db/db) showed an upregulation of PPARs signaling and fatty acid degradation pathways. Our results suggest that enhancing FAO by genetic deletion of ACC2 negatively regulates PPARs signaling through depleting endogenous PPAR ligands, which can serve as a negative feedback mechanism to prevent excess activation of PPAR signaling under non-obese condition. In obesity, excessive lipid availability negates the feedback mechanism resulting in over activation of PPAR cascade, thus contributes to the development of cardiac lipotoxicity.

A lipid droplet-associated GFP reporter-based screen identifies new fat storage regulators in C. elegans.

Fat storage disorders including obesity are pandemic human health problems. As a genetically amenable model organism, Caenorhabditis elegans has often been used to explore the molecular mechanisms of fat storage regulation. Dye staining of fixed animals and stimulated Raman scattering (SRS) microscopy methods have been used successfully to study fat storage, but a genetic screening system that takes full advantage of C. elegans transparency to perform live imaging of fluorescent protein reporters has not yet been reported. Here, we investigated the tissue-specific expression of the GFP fusion of Perilipin 1 (PLIN1), a Drosophila lipid droplet-associated protein, in C. elegans. Our results indicate that PLIN1::GFP labels lipid droplets and can be used as a fat storage indicator in live worms. Through an RNAi screen, we further identified several previously uncharacterized new fat storage regulators.

Proteomic study and marker protein identification of Caenorhabditis elegans lipid droplets.

Lipid droplets (LDs) are a neutral lipid storage organelle that is conserved across almost all species. Many metabolic syndromes are directly linked to the over-storage of neutral lipids in LDs. The study of LDs in Caenorhabditis elegans (C. elegans) has been difficult because of the lack of specific LD marker proteins. Here we report the purification and proteomic analysis of C. elegans lipid droplets for the first time. We identified 306 proteins, 63% of these proteins were previously known to be LD-proteins, suggesting a similarity between mammalian and C. elegans LDs. Using morphological and biochemical analyses, we show that short-chain dehydrogenase, DHS-3 is almost exclusively localized on C. elegans LDs, indicating that it can be used as a LD marker protein in C. elegans. These results will facilitate further mechanistic studies of LDs in this powerful genetic system, C. elegans.