Assessing the associations of 1,400 blood metabolites with major depressive disorder: a Mendelian randomization study

Background and objectivesMajor Depressive Disorder (MDD) is one of the most prevalent and debilitating health conditions worldwide. Previous studies have reported a link between metabolic dysregulation and MDD. However, evidence for a causal relationship between blood metabolites and MDD is lacking.MethodsUsing a two-sample bidirectional Mendelian randomization analysis (MR), we assessed the causal relationship between 1,400 serum metabolites and Major Depressive Disorder (MDD). The Inverse Variance Weighted method (IVW) was employed to estimate the causal association between exposures and outcomes. Additionally, MR-Egger regression, weighted median, simple mode, and weighted mode methods were used as supplementary approaches for a comprehensive appraisal of the causality between blood metabolites and MDD. Pleiotropy and heterogeneity tests were also conducted. Lastly, the relevant metabolites were subjected to metabolite function analysis, and a reverse MR was implemented to explore the potential influence of MDD on these metabolites.ResultsAfter rigorous screening, we identified 34 known metabolites, 13 unknown metabolites, and 18 metabolite ratios associated with Major Depressive Disorder (MDD). Among all metabolites, 33 were found to have positive associations, and 32 had negative associations. The top five metabolites that increased the risk of MDD were the Arachidonate (20:4n6) to linoleate (18:2n6) ratio, LysoPE(18:0/0:0), N-acetyl-beta-alanine levels, Arachidonate (20:4n6) to oleate to vaccenate (18:1) ratio, Glutaminylglutamine, and Threonine to pyruvate ratio. Conversely, the top five metabolites that decreased the risk of MDD were N6-Acetyl-L-lysine, Oleoyl-linoleoyl-glycerol (18:1 to 18:2) [2] to linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) [2] ratio, Methionine to phosphate ratio, Pregnanediol 3-O-glucuronide, and 6-Oxopiperidine-2-carboxylic acid. Metabolite function enrichment was primarily concentrated in pathways such as Bile Acid Biosynthesis (FDR=0.177), Glutathione Metabolism (FDR=0.177), Threonine, and 2-Oxobutanoate Degradation (FDR=0.177). In addition, enrichment was noted in pathways like Valine, Leucine, and Isoleucine Biosynthesis (p=0.04), as well as Ascorbate and Aldarate Metabolism (p=0.04).DiscussionWithin a pool of 1,400 blood metabolites, we identified 34 known metabolites and 13 unknown metabolites, as well as 18 metabolite ratios associated with Major Depressive Disorder (MDD). Additionally, three functionally enriched groups and two metabolic pathways were selected. The integration of genomics and metabolomics has provided significant insights for the screening and prevention of MDD

Nuclear Translocation of Jacob in Hippocampal Neurons after Stimuli Inducing Long-Term Potentiation but Not Long-Term Depression

Background: In recent years a number of potential synapto-nuclear protein messengers have been characterized that are thought to be involved in plasticity-related gene expression, and that have the capacity of importin- mediated and activity-dependent nuclear import. However, there is a surprising paucity of data showing the nuclear import of such proteins in cellular models of learning and memory. Only recently it was found that the transcription factor cyclic AMP response element binding protein 2 (CREB2) transits to the nucleus during long-term depression (LTD), but not during long-term potentiation (LTP) of synaptic transmission in hippocampal primary neurons. Jacob is another messenger that couples NMDA-receptor-activity to nuclear gene expression. We therefore aimed to study whether Jacob accumulates in the nucleus in physiological relevant models of activity-dependent synaptic plasticity. Methodology/Principal Findings: We have analyzed the dynamics of Jacob’s nuclear import following induction of NMDA-receptor dependent LTP or LTD at Schaffer collateral-CA1 synapses in rat hippocampal slices. Using time-lapse imaging of neurons expressing a Jacob-Green-Fluorescent-Protein we found that Jacob rapidly translocates from dendrites to the nucleus already during the tetanization period of LTP, but not after induction of LTD. Immunocytochemical stainings confirmed the nuclear accumulation of endogenous Jacob in comparison to apical dendrites after induction of LTP but not LTD. Complementary findings were obtained after induction of NMDA-receptor dependent chemical LTP and LTD i

Experimental and numerical investigations on cavitation bubble dynamics near a solid boundary

Cavitation bubble dynamics near a solid boundary have been studied for quite a long time, primarily in the field of hydrodynamic science, to explain the cavitation corrosion and damage observed on ship propellers and hydraulic machines. Recently, however, there has been increasing interest in applying acoustic cavitation in certain other fields, like ultrasonic cleaning, sonochemistry, shockwave lithotripsy, and sonoporation. Although the occurrence areas of these cavitation bubbles are quite different (depending on the specific field), the physical fundamentals of these processes are more or less the same. This study attempts to elucidate the corrosion/cleaning mechanism of cavitation bubbles through investigations on a single cavitation bubble dynamics near a solid boundary. The experiments on laser-induced cavitation bubble dynamics near a solid boundary were first presented. A single cavitation bubble was generated using a focused Q-switched Nd: YAG laser pulse. The bubble’s maximum expanded volume was dominated by the energy of the incident laser pulse. The inception position of the single cavitation bubble had an important influence on the bubble dynamics, which was finely controlled using a micro-translation stage. Direct observations of the bubble evolutions using a high-speed video camera revealed detailed deformations of the cavitation bubble near the solid boundary: the non-spherical bubble generation; the nearly spherical shape during the first expansion phase; the formation of a liquid jet resulting from the asymmetry of the flow field; the counterjet only appearing in a certain range of stand-off distances; the various profiles after the jet impact, etc. Indirect detections of the acoustic signals released by the oscillating bubbles, using a hydrophone system, provided a much more accurate estimation of the bubble oscillation periods than those obtained from the bubble videos captured using the high-speed camera. The statistics of the non-dimensional bubble oscillation periods could be used to roughly indicate the bubble inception positions when the maximum expanded bubble radii were known. Temporal evolutions of the bubble size were measured in this study using a novel method involving the application of AutoCAD. The energy deposited in the bubble was estimated using the maximum expanded volume after the jet impact. Following this, numerical simulation works were conducted to show some detailed bubble dynamics which could not be observed using the experimental methods. A mathematical model based on the potential flow theory was used to describe the proposed problem. An approximate perturbation method was also developed using the method of matched asymptotic expansions to include the influence of the compressibility of the liquid. It was concluded that the velocity potential near the bubble surface satisfied Laplace’s equation. A dimensionality reduction of the initial 3D potential problem to a final 1D solution was made in a cylindrical polar coordinate. Special treatments on the solid boundary and toroidal bubble were taken carefully. A numerical model based on the mixed Eulerian-Lagrangian (MEL) method and the boundary integral method (BIM) for bubble dynamics in a weakly compressible liquid near a solid boundary was created. Finally, the numerical results calculated using the MEL-BIM model were verified using available analytical results and previous numerical results. Reliable comparisons were made between the numerical results and the experimental results obtained in this study, including those for the non-spherical bubble shape, the evolution of the equivalent bubble radius, and the movement of the bubble centroid. An important advantage of the numerical method was the ability to calculate the flow field dynamics near the bubble surface. The velocity vectors and pressure contours around the bubble surface could be simulated under a fixed grid across the liquid field. The jet impact dynamics and the induced hammer pressure that impinged on the solid boundary were calculated and proved using previous experimental measurements. The formation of the counterjet was also elucidated using the numerical simulations.Doctor of Philosophy (CEE

Failure Mechanism and Mitigation Measures of the G1002 Electricity Pylon Landslide at the Jinping I Hydropower Station

On August 29 and 30, 2012, local extreme rainfalls struck the construction area of the Jinping I Hydropower Station, Xichang, China, and triggered many geohazards. The upper region of the left valley slope 200 m downstream of the dam failed and slid, exposing the D-pile of the G1002 electricity pylon and threatening the entire power transmission line. Therefore, guaranteeing the stability of the residual soil masses in the rear area of the main scarp and the safety of the G1002 electricity pylon became a primary emergency task. Geological field surveys, topographical mapping, study of the failure mechanisms, and stability evaluations were carried out from October 12, 2012, to November 7, 2013. It is revealed that the failure mechanism of the G1002 electricity pylon landslide is flood-induced tractive sliding along the interlayer between the colluvium and the bedrock, significantly influenced by heavy precipitation and frequent blasting activities during the dam construction. The residual soil masses around the G1002 electricity pylon foundation are unstable under rainfall conditions. In order to ensure the stability of the residual soil masses and pylon foundation, a mitigation measure of the anchor cables combined with lattice frame beams was proposed and applied in practice. This paper provides insights into the problems associated with the selection of the locations of electricity pylons in ravine regions as well as mitigation strategies for similar landslides

The roles of acoustic cavitations in the ultrasonic cleansing of fouled micro-membranes

This paper described the experimental studies on the de-fouling mechanism of acoustic cavitation bubbles near the fouled micro-membranes. The presence of the membrane created asymmetry in the flow field, which forced the cavitation bubble to oscillate non-spherically and finally brought forth the jet impact directed to the membrane. The oscillations and micro-jets of the cavitation bubbles enhanced the nearfield dynamic features of the fluid and improved the performance of de-fouling. The acoustic multi-bubble system is complex. In this study, the authors first focused on the individual bubble dynamics near a solid boundary. A succession of individual cavitation bubbles were created by using Q-switched Nd: YAG laser pulses. The evolutions of the bubble dynamics were observed using a high-speed camera (up to 100,000 frames per second). The pressure impulses induced by the jet impact were detected by using the hydrophone system. The pressure impulse was quite intensive as compared with the hydrostatic pressure and was strong enough to dislodge the adherent fouling elements. The authors studied the cavitation bubble dynamics for different laser energies and stand-off distances from the boundary and tried to evaluate the influence of cavitations in the ultrasonic cleaning of micro-membranes.Published versio

Discharge Characteristics and Numerical Simulation of the Oil–Gas Surface under DC Voltage

Low insulation strength at the oil–gas surface due to oil leakage and partial discharge of oil-immersed power equipment is a major threat to the safe and reliable operation of power systems. This paper investigates the initiation and development of the oil–gas surface discharge. The oil–gas surface discharge test platform was established, and discharge tests were carried out at different gap distances (1–2.5 mm). By coupling the electric field and flow field, the multi-layer dielectric discharge streamer model was built, and the characteristics of charge and electric field distribution at different gap distances were studied. The test results show that the liquid surface between the electrodes rises during the discharge process. Furthermore, the surface discharge voltage exceeds the air gap discharge voltage. With the simulation analysis, the oil–gas surface discharge is a typical streamer development process. Under 50 kV applied voltage and 2.5 mm gap distance, the average development speed of the streamer is 12.5 km/s. The larger the gap distance is, the greater the average streamer development speed is. The recording and numerical simulation of the discharge process are of great significance for exploring the mechanism of oil–gas surface discharge, optimizing the discharge process, and diagnosing partial discharges

Association between dietary sugar intake and depression in US adults: a cross-sectional study using data from the National Health and Nutrition Examination Survey 2011–2018

Abstract Background Studies examining whether diet sugar intake increases the risk of depression have produced inconsistent results. Therefore, we investigated this relationship, using the US’ National Health and Nutrition Examination Survey (NHANES) database. Methods This cross-sectional study included 18,439 adults (aged ≥ 20 years) from NHANES (2011–2018). Depressive symptoms were assessed using the nine-item version of the Patient Health Questionnaire (PHQ-9). Covariates, including age, sex, race/ethnicity, poverty-income ratio, education, marital status, hypertension, diabetes mellitus, cardiovascular disease, alcohol intake, smoking status, physical activity, and dietary energy intake, were adjusted in multivariate logistic regression models. Subgroup and threshold saturation effect analyses were performed. Results After adjusting for potential confounders, we found that a 100 g/day increase in dietary sugar intake correlated with a 28% higher prevalence of depression (odds ratio = 1.28, 95% confidence interval = 1.17–1.40, P < 0.001). Conclusion Dietary sugar intake is positively associated with depression in US adults

Association between dietary caffeine intake and severe headache or migraine in US adults

Abstract The relationship between current dietary caffeine intake and severe headache or migraine is controversial. Therefore, we investigated the association between dietary caffeine intake and severe headaches or migraines among American adults. This cross-sectional study included 8993 adults (aged ≥ 20 years) with a dietary caffeine intake from the National Health and Nutrition Examination Surveys of America from 1999 to 2004. Covariates, including age, race/ethnicity, body mass index, poverty-income ratio, educational level, marital status, hypertension, cancer, energy intake, protein intake, calcium intake, magnesium intake, iron intake, sodium intake, alcohol status, smoking status, and triglycerides, were adjusted in multivariate logistic regression models. In US adults, after adjusting for potential confounders, a 100 mg/day increase in dietary caffeine intake was associated with a 5% increase in the prevalence of severe headache or migraine (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.02–1.07). Further, the prevalence of severe headache or migraine was 42% higher with caffeine intake of ≥ 400 mg/day than with caffeine intake of ≥ 0 to < 40 mg/day (OR 1.42, 95% CI 1.16–1.75). Conclusively, dietary caffeine intake is positively associated with severe headaches or migraines in US adults