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Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.
Methods
We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).
Results
Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.
Conclusions
Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.
Depression has been linked to disruptions in resting-state networks (RSNs). However, inconsistent findings on RSN disruptions, with variations in reported connectivity within and between RSNs, complicate the understanding of the neurobiological mechanisms underlying depression.
Methods
A systematic literature search of PubMed and Web of Science identified studies that employed resting-state functional magnetic resonance imaging (fMRI) to explore RSN changes in depression. Studies using seed-based functional connectivity analysis or independent component analysis were included, and coordinate-based meta-analyses were performed to evaluate alterations in RSN connectivity both within and between networks.
Results
A total of 58 studies were included, comprising 2321 patients with depression and 2197 healthy controls. The meta-analysis revealed significant alterations in RSN connectivity, both within and between networks, in patients with depression compared with healthy controls. Specifically, within-network changes included both increased and decreased connectivity in the default mode network (DMN) and increased connectivity in the frontoparietal network (FPN). Between-network findings showed increased DMN–FPN and limbic network (LN)–DMN connectivity, decreased DMN–somatomotor network and LN–FPN connectivity, and varied ventral attention network (VAN)–dorsal attentional network (DAN) connectivity. Additionally, a positive correlation was found between illness duration and increased connectivity between the VAN and DAN.
Conclusions
These findings not only provide a comprehensive characterization of RSN disruptions in depression but also enhance our understanding of the neurobiological mechanisms underlying depression.
The maser instability associated with the loss-cone distribution has been widely invoked to explain the radio bursts observed in the astrophysical plasma environment, such as aurora and corona. In the laboratory plasma of a tokamak, events reminiscent of these radio bursts have also been frequently observed as an electron cyclotron emission (ECE) burst in the microwave range ($\mathrm{\sim }2{f_{\textrm{ce}}}$ near the last closed flux surface) during transient magnetohydrodynamic events. These bursts have a short duration of ~10 μs and display a radiation spectrum corresponding to a radiation temperature ${T_{e,\textrm{rad}}}$ of over $30\ \textrm{keV}$ while the edge thermal electron temperature ${T_e}$ is only in the range of $1\ \textrm{keV}$. Suprathermal electrons can be generated through magnetic reconnection, and a loss-cone distribution can be generated through open stochastic field lines in the magnetic mirror of the near-edge region of a tokamak plasma. Radiation modelling shows that a sharp distribution gradient $\partial f/\partial {v_ \bot } > 0$ at the loss-cone boundary can cause a negative absorption of ECE radiation through the maser instability. The negative absorption then amplifies the radiation so that the microwave intensity is significantly stronger than the thermal value. The significant ${T_{e,\textrm{rad}}}$ from the simulations suggests the potential role of the loss-cone maser instability in generating the ECE burst in a tokamak.
In this paper, we investigate a sink-driven three-layer flow in a radial Hele-Shaw cell. The three fluids are of different viscosities, with one fluid occupying an annulus-like domain, forming two interfaces with the other two fluids. Using a boundary integral method and a semi-implicit time stepping scheme, we alleviate the numerical stiffness in updating the interfaces and achieve spectral accuracy in space. The interaction between the two interfaces introduces novel dynamics leading to rich pattern formation phenomena, manifested by two typical events: either one of the two interfaces reaches the sink faster than the other (forming cusp-like morphology), or they come very close to each other (suggesting a possibility of interface merging). In particular, the inner interface can be wrapped by the other to have both scenarios. We find that multiple parameters contribute to the dynamics, including the width of the annular region, the location of the sink, and the mobilities of the fluids.
In this paper, a high-level Green–Naghdi (HLGN) model for large-amplitude internal waves in a two-layer fluid system, where the upper-fluid layer is of finite depth and the lower-fluid layer is of infinite depth, is developed under the rigid-lid free-surface approximation. The equations of the present HLGN model follow Euler's equations under the sole assumption that the horizontal and vertical velocity distributions along the vertical column are presented by known shape functions for each layer. The linear dispersion relations of the HLGN model for different levels are presented and compared with those obtained by other strongly nonlinear models for deep water, including the fully nonlinear models that include the dispersion effects $O(\mu )$ (where $\mu$ is the ratio of the upper-fluid layer depth to a typical wavelength) derived by Choi & Camassa (Phys. Rev. Lett., vol. 77, 1996, pp. 1759–1762) and $O(\mu ^2)$ derived by Debsarma et al. (J. Fluid Mech., vol. 654, 2010, pp. 281–303). It is shown that the HLGN model has a wider application range than other models. Solutions of travelling large-amplitude internal solitary waves in the absence and presence of background shear-current are then investigated by using the HLGN model. For the no-current cases, results obtained by the HLGN model show better agreement with Euler's solution on wave profile, velocity profile at the maximum interface displacement and wave speed compared with those obtained by other models. For the background shear-current cases, results obtained by the HLGN model also show good agreement with those obtained by solving the Dubreil-Jacotin–Long equation.
As an important component of prehistoric subsistence, an understanding of bone-working is essential for interpreting the evolution of early complex societies, yet worked bones are rarely systematically collected in China. Here, the authors apply multiple analytical methods to worked bones from the Longshan site of Pingliangtai, in central China, showing that Neolithic bone-working in this area, with cervid as the main raw material, was mature but localised, household-based and self-sufficient. The introduction of cattle in the Late Neolithic precipitated a shift in bone-working traditions but it was only later, in the Bronze Age, that cattle bones were utilised in a specialised fashion and dedicated bone-working industries emerged in urban centres.
To meet the demands of laser-ion acceleration at a high repetition rate, we have developed a comprehensive diagnostic system for real-time and in situ monitoring of liquid sheet targets (LSTs). The spatially resolved rapid characterizations of an LST’s thickness, flatness, tilt angle and position are fulfilled by different subsystems with high accuracy. With the help of the diagnostic system, we reveal the dependence of thickness distribution on collision parameters and report the 238-nm liquid sheet generated by the collision of two liquid jets. Control methods for the flatness and tilt angle of LSTs have also been provided, which are essential for applications of laser-driven ion acceleration and others.
Here, we report the generation of MeV alpha-particles from H-11B fusion initiated by laser-accelerated boron ions. Boron ions with maximum energy of 6 MeV and fluence of 109/MeV/sr@5 MeV were generated from 60 nm-thick self-supporting boron nanofoils irradiated by 1 J femtosecond pulses at an intensity of 1019 W/cm2. By bombarding secondary hydrogenous targets with the boron ions, 3 × 105/sr alpha-particles from H-11B fusion were registered, which is consistent with the theoretical yield calculated from the measured boron energy spectra. Our results demonstrated an alternative way toward ultrashort MeV alpha-particle sources employing compact femtosecond lasers. The ion acceleration and product measurement scheme are referential for the studies on the ion stopping power and cross section of the H-11B reaction in solid or plasma.
With the advantages of short duration and extreme brightness, laser proton accelerators (LPAs) show great potential in many fields for industrial, medical, and research applications. However, the quality of current laser-driven proton beams, such as the broad energy spread and large divergence angle, is still a challenge. We use numerical simulations to study the propagation of such proton bunches in the plasma. Results show the bunch will excite the wakefield and modulate itself. Although a small number of particles at the head of the bunch cannot be manipulated by the wakefield, the total energy spread is reduced. Moreover, while reducing the longitudinal energy spread, the wakefield will also pinch the beam in the transverse direction. The space charge effect of the bunch is completely offset by the wakefield, and the transverse momentum of the bunch decreases as the bunch transports in the plasma. For laser-driven ion beams, our study provides a novel idea about the optimization of these beams.
The global transition towards diets high in calories has contributed to 2.1 billion people becoming overweight, or obese, which damages male reproduction and harms offspring. Recently, more and more studies have shown that paternal exposure to stress closely affects the health of offspring in an intergenerational and transgenerational way. SET Domain Containing 2 (SETD2), a key epigenetic gene, is highly conserved among species, is a crucial methyltransferase for converting histone 3 lysine 36 dimethylation (H3K36me2) into histone 3 lysine 36 trimethylation (H3K36me3), and plays an important regulator in the response to stress. In this study, we compared patterns of SETD2 expression and the H3K36me3 pattern in pre-implantation embryos derived from normal or obese mice induced by high diet. The results showed that SETD2 mRNA was significantly higher in the high-fat diet (HFD) group than the control diet (CD) group at the 2-cell, 4-cell, 8-cell, and 16-cell stages, and at the morula and blastocyst stages. The relative levels of H3K36me3 in the HFD group at the 2-cell, 4-cell, 8-cell, 16-cell, morula stage, and blastocyst stage were significantly higher than in the CD group. These results indicated that dietary changes in parental generation (F0) male mice fed a HFD were traceable in SETD2/H3K36me3 in embryos, and that a paternal high-fat diet brings about adverse effects for offspring that might be related to SETD2/H3K36me3, which throws new light on the effect of paternal obesity on offspring from an epigenetic perspective.
Galls function as provide shelter for gall inducers, guarding them against their natural enemies. Previous research has illuminated the interactions between galls, gall inducers, and their corresponding parasitoids within various caltrop plants. However, less is known about these relationships within Nitraria sibirica, particularly regarding the efficacy of parasitism. Therefore, this study aimed to identify the morphometric relationships among the swollen galls, gall inducers, and their parasitoids. Two species of gall inducers and three species of parasitoids were obtained from the swollen galls of N. sibirica. The correlations of the parasitization indexes, the lifespan of gall inhabitants, and temperature and the morphometric relationships between the galls and their inhabitants were analyzed. The dominant gall inducer identified was Contarinia sp. (Diptera: Cecidomyiidae). Furthermore, it was observed that three solitary parasitoids attacked Contarinia sp. in the swollen galls, with only Eupelmus gelechiphagus acting as an idiobiont ectoparasitoid. The dominant parasitoids were Platygaster sp. and Cheiloneurus elegans at sites 1 and 2, respectively, with Platygaster sp. displaying greater abundance than C. elegans in the swollen galls. The lifespan of the gall inhabitants shortened gradually as the temperature increased. Moreover, the optimal number of gall chambers ranged from two to four per swollen gall with maximized fitness, which can be considered the optimal population density for the gall inducer Contarinia sp. Morphometric analysis exhibited a strong linear correlation between gall size and chamber number or the number of gall inhabitants, as well as a weak correlation between gall size and body size of the primary inhabitants of swollen galls. Our results highlight the importance of the biological investigation of parasitoids and gall inducers living in closed galls with multiple chambers and may pave the way for potential application in biological control.
Post-acceleration of protons in helical coil targets driven by intense, ultrashort laser pulses can enhance ion energy by utilizing the transient current from the targets’ self-discharge. The acceleration length of protons can exceed a few millimeters, and the acceleration gradient is of the order of GeV/m. How to ensure the synchronization between the accelerating electric field and the protons is a crucial problem for efficient post-acceleration. In this paper, we study how the electric field mismatch induced by current dispersion affects the synchronous acceleration of protons. We propose a scheme using a two-stage helical coil to control the current dispersion. With optimized parameters, the energy gain of protons is increased by four times. Proton energy is expected to reach 45 MeV using a hundreds-of-terawatts laser, or more than 100 MeV using a petawatt laser, by controlling the current dispersion.
In recent years, the incidence of teratospermia has been increasing, and it has become a very important factor leading to male infertility. The research on the molecular mechanism of teratospermia is also progressing rapidly. This article briefly summarizes the clinical incidence of teratozoospermia, and makes a retrospective summary of related studies reported in recent years. Specifically discussing the relationship between gene status and spermatozoa, the review aims to provide the basis for the genetic diagnosis and gene therapy of teratozoospermia.
Electronic skin (e-skin) is playing an increasingly important role in health detection, robotic teleoperation, and human-machine interaction, but most e-skins currently lack the integration of on-site signal acquisition and transmission modules. In this paper, we develop a novel flexible wearable e-skin sensing system with 11 sensing channels for robotic teleoperation. The designed sensing system is mainly composed of three components: e-skin sensor, customized flexible printed circuit (FPC), and human-machine interface. The e-skin sensor has 10 stretchable resistors distributed at the proximal and metacarpal joints of each finger respectively and 1 stretchable resistor distributed at the purlicue. The e-skin sensor can be attached to the opisthenar, and thanks to its stretchability, the sensor can detect the bent angle of the finger. The customized FPC, with WiFi module, wirelessly transmits the signal to the terminal device with human-machine interface, and we design a graphical user interface based on the Qt framework for real-time signal acquisition, storage, and display. Based on this developed e-skin system and self-developed robotic multi-fingered hand, we conduct gesture recognition and robotic multi-fingered teleoperation experiments using deep learning techniques and obtain a recognition accuracy of 91.22%. The results demonstrate that the developed e-skin sensing system has great potential in human-machine interaction.
Mounting evidence showed that insula contributed to the neurobiological mechanism of suicidal behaviors in bipolar disorder (BD). However, no studies have analyzed the dynamic functional connectivity (dFC) of insular Mubregions and its association with personality traits in BD with suicidal behaviors. Therefore, we investigated the alterations of dFC variability in insular subregions and personality characteristics in BD patients with a recent suicide attempt (SA).
Methods
Thirty unmedicated BD patients with SA, 38 patients without SA (NSA) and 35 demographically matched healthy controls (HCs) were included. The sliding-window analysis was used to evaluate whole-brain dFC for each insular subregion seed. We assessed between-group differences of psychological characteristics on the Minnesota Multiphasic Personality Inventory-2. Finally, a multivariate regression model was adopted to predict the severity of suicidality.
Results
Compared to NSA and HCs, the SA group exhibited decreased dFC variability values between the left dorsal anterior insula and the left anterior cerebellum. These dFC variability values could also be utilized to predict the severity of suicidality (r = 0.456, p = 0.031), while static functional connectivity values were not appropriate for this prediction. Besides, the SA group scored significantly higher on the schizophrenia clinical scales (p < 0.001) compared with the NSA group.
Conclusions
Our findings indicated that the dysfunction of insula–cerebellum connectivity may underlie the neural basis of SA in BD patients, and highlighted the dFC variability values could be considered a neuromarker for predictive models of the severity of suicidality. Moreover, the psychiatric features may increase the vulnerability of suicidal behavior.
Evidence of couples’ BMI and its influence on birth weight is limited and contradictory. Therefore, this study aims to assess the association between couple’s preconception BMI and the risk of small for gestational age (SGA)/large for gestational age (LGA) infant, among over 4·7 million couples in a retrospective cohort study based on the National Free Pre-pregnancy Checkups Project between 1 December 2013 and 30 November 2016 in China. Among the live births, 256 718 (5·44 %) SGA events and 506 495 (10·73 %) LGA events were documented, respectively. After adjusting for confounders, underweight men had significantly higher risk (OR 1·17 (95 % CI 1·15, 1·19)) of SGA infants compared with men with normal BMI, while a significant and increased risk of LGA infants was obtained for overweight and obese men (OR 1·08 (95 % CI 1·06, 1·09); OR 1·19 (95 % CI 1·17, 1·20)), respectively. The restricted cubic spline result revealed a non-linear decreasing dose–response relationship of paternal BMI (less than 22·64) with SGA. Meanwhile, a non-linear increasing dose–response relationship of paternal BMI (more than 22·92) with LGA infants was observed. Moreover, similar results about the association between maternal preconception BMI and SGA/LGA infants were obtained. Abnormal preconception BMI in either women or men were associated with increased risk of SGA/LGA infants, respectively. Overall, couple’s abnormal weight before pregnancy may be an important preventable risk factor for SGA/LGA infants.
Previous studies have demonstrated structural and functional changes of the hippocampus in patients with major depressive disorder (MDD). However, no studies have analyzed the dynamic functional connectivity (dFC) of hippocampal subregions in melancholic MDD. We aimed to reveal the patterns for dFC variability in hippocampus subregions – including the bilateral rostral and caudal areas and its associations with cognitive impairment in melancholic MDD.
Methods
Forty-two treatment-naive MDD patients with melancholic features and 55 demographically matched healthy controls were included. The sliding-window analysis was used to evaluate whole-brain dFC for each hippocampal subregions seed. We assessed between-group differences in the dFC variability values of each hippocampal subregion in the whole brain and cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB). Finally, association analysis was conducted to investigate their relationships.
Results
Patients with melancholic MDD showed decreased dFC variability between the left rostral hippocampus and left anterior lobe of cerebellum compared with healthy controls (voxel p < 0.005, cluster p < 0.0125, GRF corrected), and poorer cognitive scores in working memory, verbal learning, visual learning, and social cognition (all p < 0.05). Association analysis showed that working memory was positively correlated with the dFC variability values of the left rostral hippocampus-left anterior lobe of the cerebellum (r = 0.338, p = 0.029) in melancholic MDD.
Conclusions
These findings confirmed the distinct dynamic functional pathway of hippocampal subregions in patients with melancholic MDD, and suggested that the dysfunction of hippocampus-cerebellum connectivity may be underlying the neural substrate of working memory impairment in melancholic MDD.
Ebselen is a well-known synthetic compound mimicking glutathione peroxidase (GPx), which catalyses some vital reactions that protect against oxidative damage. Based on a large number of in vivo and in vitro studies, various mechanisms have been proposed to explain its actions on multiple targets. It targets thiol-related compounds, including cysteine, glutathione, and thiol proteins (e.g., thioredoxin and thioredoxin reductase). Owing to this, ebselen is a unique multifunctional agent with important effects on inflammation, apoptosis, oxidative stress, cell differentiation, immune regulation and neurodegenerative disease, with anti-microbial, detoxifying and anti-tumour activity. This review summarises the current understanding of the multiple biological processes and molecules targeted by ebselen, and its pharmacological applications.
To explore the accuracy of estimated 24-h urinary iodine excretion (24-h UIEest) in assessing iodine nutritional status.
Design:
Fasting venous blood, 24-h and spot urine samples were collected during the day. The urinary iodine concentration (UIC) and urinary creatinine concentration (UCrC) were measured, and the urinary iodine-to-creatinine ratio (UI/Cr), 24-h UIEest, and 24-h urinary iodine excretion (24-h UIE) were calculated. At the population level, correlation and consistency between UIC, UI/Cr, 24-h UIEest and 24-h UIE were assessed using correlation analysis and Bland–Altman plots. At the individual level, receiver operating characteristic (ROC) curves were used to analyse the accuracy of the above indicators for evaluating insufficient and excessive iodine intake. The reference interval of 24-h UIEest was established based on percentile values.
Setting:
Indicator can accurately evaluate individual iodine nutrition during pregnancy remains controversial.
Participants:
Pregnant women (n 788).
Results:
Using 24-h UIE as standard, the correlation coefficients of 24-h UIEest from different periods of the day ranged from 0·409 to 0·531, and the relative average differences ranged from 4·4 % to 10·9 %. For diagnosis of insufficient iodine intake, the area under the ROC curve of 24-h UIEest was 0·754, sensitivity and specificity were 79·6 % and 65·4 %, respectively. For diagnosis of excessive iodine intake, the area of 24-h UIEest was 0·771, sensitivity and specificity were 66·7 % and 82·0 %, respectively. The reference interval of 24-h UIEest was 58·43–597·65 μg.
Conclusions:
Twenty-four-hour UIEest can better indicate iodine nutritional status at a relatively large sample size in a given population of pregnant women. It can be used for early screening at the individual level to obtain more lead time for pregnant women.