Wet scavenging of multi-mode 137Cs aerosols following the Fukushima accident: Size-resolved microphysics modeling with observed diameters.

Wet scavenging was critical in the atmospheric transport of 137Cs aerosols following the Fukushima accident. The aerosol size diversity and related microphysical processes produce complex behaviors during wet scavenging. Such behaviors are difficult to investigate using traditional simplified size distributions, resulting in inaccurate modeling. This study establishes an improved size-resolved wet scavenging model that considers the activation process. Using this model, five monodisperse simulations with five representative observed diameters with realistic solubility setting are performed to investigate the spatiotemporal wet scavenging behaviors of 137Cs aerosols. One polydisperse simulation with an empirical size distribution is also validated against the observation. The results reveal that 137Cs aerosols with diameters of 0.6 and 2.0 µm are mainly subject to below-cloud scavenging, which makes a significant contribution to low-deposition areas (<300 kBq/m2). For 137Cs aerosols with diameters of 6.4, 15, and 30 µm, in-cloud scavenging dominates, and the resulting depositions make significant contributions in high-deposition areas. The polydisperse results satisfy the criteria for good performance and better agree with the size, and deposition observations than the five monodisperse simulations, whereas for the concentration, the results show a similar RANK2 with the best mono1 and mono2 cases and reach the satisfactory criteria. These findings reveal the complex behavior and wet scavenging process of multi-mode 137Cs aerosols, improving our understanding and modeling.

Curcumin alleviates traumatic brain injury induced by gas explosion through modulating gut microbiota and suppressing the LPS/TLR4/MyD88/NF-κB pathway.

Gas explosions (GE) are a prevalent and widespread cause of traumatic brain injury (TBI) in coal miners. However, the impact and mechanism of curcumin on GE-induced TBI in rats remain unclear. In this study, we simulated GE-induced TBI in rats and administered curcumin orally at a dose of 100 mg/kg every other day for 7 days to modulate the gut microbiota in TBI rats. We employed 16S rRNA sequencing and LC-MS/MS metabolomic analysis to investigate changes in the intestinal flora and its metabolic profile. Additionally, we utilized ELISA, protein assays, and immunohistochemistry to assess neuroinflammatory signaling molecules for validation. In a rat TBI model, GE resulted in weight loss, pathological abnormalities, and cortical hemorrhage. Treatment with curcumin significantly mitigated histological abnormalities and microscopic mitochondrial structural changes in brain tissue. Furthermore, curcumin treatment markedly ameliorated GE-induced brain dysfunction by reducing the levels of several neuroinflammatory signaling molecules, including neuron-specific enolase, interleukin (IL)-1ß, IL-6, and cryptothermic protein 3. Notably, curcumin reshaped the gut microbiome by enhancing evenness, richness, and composition. Prevotella_9, Alloprevotella, Bacilli, Lactobacillales, Proteobacteria, and Gammaproteobacteria were identified as prominent members of the gut microbiota, increasing the linear discriminant analysis scores and specifically enhancing the abundance of bacteria involved in the nuclear factor (NF)-κB signaling pathway, such as Lachnospiraceae and Roseburia. Additionally, there were substantial alterations in serum metabolites associated with metabolic NF-κB signaling pathways in the model group. Curcumin administration reduced serum lipopolysaccharide levels and downregulated downstream Toll-like receptor (TLR)4/myeloid differentiation primary response 88 (MyD88)/NF-κB signaling. Furthermore, curcumin alleviated GE-induced TBI in rats by modulating the gut microbiota and its metabolites. Based on these protective effects, curcumin may exert its influence on the gut microbiota and the TLR4/MyD88/NF-κB signaling pathways to ameliorate GE-induced TBI.

Multi-scenario validation of the robust inversion method with biased plume range and values.

Release rate estimation is a vital means of revealing the emission process of radionuclides and assessing the environmental consequences in an emergency. Inverse modeling is widely used in emergency cases, but is vulnerable to plume biases in atmospheric dispersion modeling. One promising solution is a model called "Simultaneously Estimates the Release rate And Corrects both the plume range and Transport pattern" (SERACT). This study investigates the feasibility and behavior of SERACT based on four wind tunnel experiments replicating complex dispersion scenarios with both dense buildings and heterogeneous topography. SERACT's performance is compared with that of Tikhonov-regularized inversion and its predecessor. The results demonstrate that SERACT successfully corrects the modeled plume biases and simultaneously improves the release rate estimations in all four complex local-scale scenarios. The release rates retrieved by SERACT provide better agreement with the true release rates than those given by the other methods for all scenarios, with an average deviation of only 5.83%. After correction, the simulated plume reproduces the concentrations at all sites and achieves the best Pearson correlation coefficient (1.00) and fraction of simulations within a factor of 2 of the measurements (1.00); these values are 7.33 and 2.09 times higher, respectively, than those of simulations using release rates obtained using Tikhonov-regularized inversion.

Local atmospheric transport behaviors of representative radionuclides during the Fukushima accident: A 200-m-resolution cross-scale study from site to 20 km.

Modeling of local atmospheric radionuclide transport is essential for nuclear emergency response. However, very few studies of the Fukushima Dai-ichi nuclear power plant (FDNPP) accident have focused on this topic because of the complex meteorology and the cross-scale transport behaviors from the site to 20 km of the FDNPP. In this study, both the local meteorology and transport behaviors were investigated at high resolution (200 m) using ensembles of different meteorology and models. Four wind fields calculated from onsite observations and three regional-scale meteorological fields (i.e., the 1-km ECMWF, 3-km and 1-km NHM-LETKF), and two transport models: the RIMPUFF Lagrangian puff model and the SPRAY particle model were considered and combined with each other. These eight simulations and their ensemble mean were analyzed based on onsite observations of wind and gamma dose rates, and local-scale observations of 137Cs concentration. Results revealed that at the site, the Onsite wind field which captured the frequently changing wind, best reproduced the onsite gamma dose rates with the grid resolution of 200 m. At the local scale (up to 20 km), the observations present a smoother temporal change. The wind fields assimilated with Japanese domestic observations presented advantageous performance, and the 1-km NHM-LETKF achieved the best score of the factor of 5 metric of 0.49 for the simulated 137Cs concentration. The SPRAY coupled with the three-dimensional (3D) convolution method and RIMPUFF showed better performance in simulating the onsite gamma dose rate and the local-scale concentration, respectively. The ensemble mean achieved robust metrics, better simulated the baseline of onsite gamma dose rates, and reproduced more peaks of local-scale concentration at the expense of peak value deviation.

Model behavior regarding in- and below-cloud 137Cs wet scavenging following the Fukushima accident using 1-km-resolution meteorological field data.

Wet deposition remains an important source of uncertainty in modeling of the atmospheric transport of 137Cs following the Fukushima Daiichi Nuclear Power Plant accident. Its behavior is often difficult to investigate owing to the limited resolution of meteorological field data and inconsistent model implementations. This study investigated the detailed behavior of 25 combinations of in- and below-cloud wet scavenging models using high-resolution (1 km × 1 km) meteorological input. These combinations were all implemented in the Weather Research and Forecasting-Chemistry model, thereby enabling consistent evaluation. The 1-km-resolution simulations were compared with simulations obtained previously using 3-km-resolution meteorological field data. Results revealed that rainfall of <1 mm/h is critical for simulation accuracy. The 1-km results revealed better representation of rainfall than that revealed by the 3-km results, but with spatiotemporal variability in accuracy. Owing to their sensitivity to rainfall, single-parameter wet deposition models showed improvements in performance in the 1-km simulations relative to that in the 3-km simulations. The multiparameter models showed more robust performance in terms of both simulations, and the Roselle-Mircea model presented the best performance among the 25 models considered. Wind transport showed substantial influence on the removal of atmospheric 137Cs, and it was nonnegligible even during periods in which wet deposition was dominant. The 1-km-resolution simulations effectively reproduced local-scale 137Cs concentrations but with deviations in timing, mainly because of biased wind direction. These findings indicate the necessity for a refined wind and dispersion model for local-scale simulation of 137Cs concentration.

Objective inversion of the continuous atmospheric 137Cs release following the Fukushima accident.

Eleven years after the Fukushima accident, independent objective estimates of the atmospheric 137Cs release still suffer from discontinuities such as negative release terms, oscillations, and temporal gaps, leading to noticeable differences from the subjective estimate. This paper describes an objective method that handles these artifacts and promotes the continuity of releases at fine resolutions. The proposed method uses the joint estimation model to reduce the oscillations induced by the model-observation discrepancies, and employs total variation regularization to recover the missing releases caused by insufficient observations. Adaptive parameterization is used to correct negative values. The application of this method to the Fukushima accident produces a source term that accurately approximates continuous releases at a fine temporal resolution of 1 h, providing a better match with the recognized subjective source term than nine published estimates, with a Pearson's correlation coefficient of 0.923 and an index of agreement of 0.872. This source term agrees with the timing of on-site gamma dose rate peaks, significantly improving the air concentration and deposition simulations, with FAC10 values of 0.564 and 0.990, respectively. The estimation error varies smoothly in a limited range with different regularization parameters, enabling automatic parameterization and demonstrating the potential for operational inversions.

Inversion of 137Cs emissions following the fukushima accident with adaptive release recovery for temporal absences of observations.

Temporal absences in observation records lead to release losses during the source term inversions of atmospheric radionuclide emissions. Consequently, objectively-estimated source terms for the Fukushima accident contain fewer release details and present large discrepancies when compared with the expert-judged one. This paper describes an objective method that can adaptively recover the missing releases caused by the temporal absences of observations. The proposed method assumes that the accident releases of radionuclides are piecewise-constant and comprise both peaks and constant releases. The missing releases are adaptively recovered as either peaks or constant releases by minimizing the total variation of the estimated source term. The proposed method is applied to the Fukushima accident and evaluated against regional airborne and deposited 137Cs observations. The results demonstrate that this method effectively recovers the missing releases, producing a source term that matches the timing of both on-site gamma dose rate peaks and accident events. The retrieved source term improves the simulation of air concentrations and reproduces most of the deposition patterns. This is the first time that an objective method has independently reproduced the details in the expert-judged one for the Fukushima accident.

[Effect of methotrexate on the urinary proteome of rats].

Methotrexate (MTX) is a widely used immunosuppressive drug. Large-dose of MTX is used for the treatment of cancer while low-dose is used for the treatment of rheumatoid arthritis (RA). This study aimed to explore the effect of MTX on the urinary proteome of rats. MTX was given to rats orally to construct an MTX intragastric administration rat model. The urine of the rats were collected within 10 hours after giving MTX, and the urine proteins of the rats were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). A total of 31 differential proteins were identified, of which 7 proteins were related to the effect MTX and the symptom of RA. The biological processes of some rats reflected the effect of MTX on the body's glutathione metabolism and the JAK/STAT signaling pathway, which indicated that urine proteins have the ability to reflect the effects of MTX on the body of rats. The spectrum of the differential proteins of each single rat showed that different individuals respond to the drug quite differently.

Metformin mitigates gas explosion-induced blast lung injuries through AMPK-mediated energy metabolism and NOX2-related oxidation pathway in rats.

Gas explosions are a recurrent event in coal mining that cause severe pulmonary damage due to shock waves, and there is currently no effective targeted treatment. To illustrate the mechanism of gas explosion-induced lung injury and to explore strategies for blast lung injury (BLI) treatment, the present study used a BLI rat model and supplementation with metformin (MET), an AMP-activated protein kinase (AMPK) activator, at a dose of 10 mg/kg body weight by intraperitoneal injection. Protein expression levels were detected by western blotting. Significantly decreased expression of phosphorylated (p)-AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and metabolic activity were observed in the BLI group compared with those in the control group. However, the mitochondrial stability, metabolic activity and expression of p-AMPK and PGC1α were elevated following MET treatment. These results suggested that MET could attenuate gas explosion-induced BLI by improving mitochondrial homeostasis. Meanwhile, high expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX2) and low expression of catalase (CAT) were observed in the BLI group. The expression levels of NOX2 and CAT were restored in the BLI + MET group relative to changes in the BLI group, and the accumulation of oxidative stress was successfully reversed following MET treatment. Overall, these findings revealed that MET could alleviate BLI by activating the AMPK/PGC1α pathway and inhibiting oxidative stress caused by NOX2 activation.

Theta-Burst Stimulation Combined With Virtual-Reality Reconsolidation Intervention for Methamphetamine Use Disorder: Study Protocol for a Randomized-Controlled Trial.

Background: Craving associated with drug-related memory is one of the key factors that induce the relapse of methamphetamine (MA). Disruption or modulation of the reconsolidation of drug-related memory may serve as an option for clinical treatment of MA addiction. This protocol proposes to use virtual reality (VR) to retrieve drug-associated memory and then use transcranial magnetic stimulation (TMS) at the neural circuit that encodes the reward value of drug cues to provide a non-invasive intervention during reconsolidation. We aim to evaluate the effectiveness of TMS treatment after VR retrieval on the reduction of cue reactivity and craving of MA. Methods: This is a randomized, double-blind, sham-controlled, parallel group trial, targeting participants with MA use disorder aged from 18 to 45 years old. Forty-five eligible volunteers in Shanxi Drug Rehabilitation Center will be recruited and be randomly allocated into three parallel groups, receiving either 1) MA-related cues retrieval in VR combined with active TMS (MA VR scene + TBS) or 2) sham TMS (MA VR scene + sham TBS), or 3) neutral cues retrieval in VR combined with active TMS (neutral VR scene + TBS). Two sessions of post-VR-retrieval TBS will be scheduled on two separate days within 1 week. The primary outcome will detect the memory-related activity by the electroencephalography (EEG) reactivity to drug cues in VR scenes. Secondary outcomes are the self-reported MA craving in VR scene, the physiological parameter (cue-induced heart rate) and the scores of psychological questionnaires including anxiety, depression, and mood. All primary and secondary outcomes will be assessed at baseline, 1-week, and 1-month post-intervention. Assessments will be compared between the groups of 1) MA VR scene + TBS, 2) MA VR scene + sham TBS and 3) neutral VR scene + TBS. Discussion: This will be the first study to examine whether the TMS modulation after VR retrieval can reduce self-reported craving and drug-related cue reactivity. It will promote the understanding of the neural circuit mechanism of the reconsolidation-based intervention and provide an effective treatment for MA use disorder patients. Clinical Trial Registration: [Chinese Clinical Trial Registry], identifier [ChiCTR1900026902]. Registered on 26 October 2019.

Alterations in the gut microbiota and its metabolic profile of PM2.5 exposure-induced thyroid dysfunction rats.

Fine particulate matter (PM2.5) has drawn more and more interest due to its adverse effects on health. Thyroid has been demonstrated to be the key organ impacted by PM2.5. However, the mechanisms for PM2.5 exposure-induced thyrotoxicity remain unclear. To explore the mechanisms, a rat thyroid injury model was established by exposing rats to PM2.5 via passive pulmonary inhalation. Thyroid hormones and thyroid function proteins were detected. The thyroid function affected by PM2.5 exposure was investigated via metabolomics analysis using liquid chromatography-mass spectrometry and 16S rRNA gene sequencing. Results showed that PM2.5 exposure induced remarkable alterations in gut microbiome evenness, richness, and composition. Metabolomics profiling revealed that the urine metabolites levels were changed by PM2.5 exposure. The altered gut microbiota and urine metabolites showed significant correlations with thyroid function indicators (total T3, total T4 and thyrotropin hormone, etc.). These metabolites were involved in metabolic pathways including thyroid hormone synthesis, metabolisms of tryptophan, d-Glutamine and D-glutamate, histidine, glutathione, etc. The altered gut microbiota showed significant correlations with urine metabolites (glutathione, citric acid, D-Glutamic acid, kynurenic acid and 5-Aminopentanoic acid, etc.). For example, the taurocholic acid levels positively correlated with the relative abundance of several genera including Elusimicrobium (r = 0.9741, p = 0.000000), Muribaculum (r = 0.9886, p = 0.000000), Candidatus_Obscuribacter (r = 0.8423, p = 0.000585), Eubacterium (r = 0.9237, p = 0.000017), and Parabacteroides (r = 0.8813, p = 0.000150), while it negatively correlated with the relative abundance of Prevotella (r = -0.8070, p = 0.001509). PM2.5 exposure-induced thyrotoxicity led to remarkable alterations both in gut microbiome composition and some metabolites involved in metabolic pathways. The altered intestinal flora and metabolites can in turn influence thyroid function in rats. These findings may provide novel insights regarding perturbations of the gut-thyroid axis as a new mechanism for PM2.5 exposure-induced thyrotoxicity.

Protective effects of curcumin against thyroid hormone imbalance after gas explosion-induced traumatic brain injury via activation of the hypothalamic-pituitary-thyroid axis in male rats.

Gas explosion (GE)-induced traumatic brain injury (TBI) can affect thyroid hormone (TH) homeostasis in miners. This study evaluated the effects of hepatic transthyretin and hypothalamic-pituitary-thyroid (HPT) axis on thyroids and explored the protective effect and mechanism of curcumin on GE-induced TBI. Thirty rats were randomly divided into three groups (10 per group): first group (control group)-rats received GE treatment once; second group (GE group)-rats received GE treatment (200 m from the source of the explosion once); third group (GE + Cur group)-rats received curcumin (Cur) by lavage at a dose of 100 mg/kg/day once every other day for 7 days after receiving GE. After GE, the pathological changes were analyzed by hemotoxylin and eosin staining, and the levels of serum reactive oxygen species (ROS), urine iodine (UI), THs, nuclear factor-kappa B (NF-κB), superoxide dismutase (SOD), glutathione peroxidase (Gpx), and malondialdehyde (MDA) were analyzed using ELISA. Expression of proteins in the HPT axis of rats was examined by immunohistochemistry and Western blotting. We found that GE could induce pathologic changes in rat thyroid and liver. Serum levels of THs, NF-κB and serum redox state became unbalanced in rats after GE. GE could inhibit the biosynthesis and biotransformation of THs by affecting key HPT axis proteins. Additionally, GE reduced the level of hepatic transthyretin. Serum THs levels and thyroid sections were almost recovered to normal after curcumin treatment. The aforementioned key HPT axis proteins in the curcumin group showed opposite expression trends. In summary, GE affected THs balance while curcumin can protect against these injury effects by affecting TH biosynthesis, biotransformation, and transport, and inducing oxidative stress and inflammatory responses.

Extensive divergence of projections to the forebrain from neurons in the paraventricular nucleus of the thalamus.

Neurons in the paraventricular nucleus of the thalamus (PVT) respond to emotionally salient events and project densely to subcortical regions known to mediate adaptive behavioral responses. The areas of the forebrain most densely innervated by the PVT include striatal-like subcortical regions that consist of the shell of the nucleus accumbens (NAcSh), the dorsolateral region of the bed nucleus of the stria terminalis (BSTDL) and the lateral-capsular division of the central nucleus of the amygdala (CeL). A recent tracing experiment demonstrated that the PVT is composed of two intermixed populations of neurons that primarily project to either the dorsomedial (dmNAcSh) or ventromedial region of the NAcSh (vmNAcSh) with many of the vmNAcSh projecting neurons providing collateral innervation of the BSTDL and CeL. The present study used triple injections of the retrograde tracer cholera toxin B to provide a detailed map of the location of PVT neurons that provide collaterals to the vmNAcSh, BSTDL and CeL. These neurons were intermixed throughout the PVT and did not form uniquely localized subpopulations. An intersectional viral anterograde tracing approach was used to demonstrate that regardless of its presumed target of innervation (dmNAcSh, vmNAcSh, BSTDL, or CeL), most neurons in the PVT provide collateral innervation to a common set of forebrain regions. The paper shows that PVT-dmNAcSh projecting neurons provide the most divergent projection system and that these neurons express the immediate early gene product cFos following an aversive incident. We propose that the PVT may regulate a broad range of responses to physiological and psychological challenges by simultaneously influencing functionally diverse regions of the forebrain that include the cortex, striatal-like regions in the basal forebrain and a number of hypothalamic nuclei.

Multi-scenario validation of CALMET-RIMPUFF for local-scale atmospheric dispersion modeling around a nuclear powerplant site with complex topography.

The CALMET-RIMPUFF is composed of the California Meteorological Model and the Risø Mesoscale PUFF model, which provides refined atmospheric dispersion modeling for nuclear emergency response. Because the performance of an atmospheric dispersion model can be case-sensitive, a multi-scenario validation is important to understand a model's behavior and limits. In this study, a multi-scenario validation of CALMET-RIMPUFF was performed based on six wind tunnel experiments simulating a real China's nuclear powerplant site with complex topographies and dense buildings. The CALMET-RIMPUFF simulations were compared with the measurements of the vertical wind profiles, 2D ground wind and concentration fields, both qualitatively and quantitatively. The results demonstrate that the CALMET-RIMPUFF can simulate the ground-level wind with acceptable accuracies. For vertical wind profiles, the accuracies show high dependencies on the local topography and building layout. The simulated ground concentrations generally agree well with the measurements, though the plume axis showed slight discrepancies from the measurements in three cases. Because the CALMET-RIMPUFF lacks a building effect module, it shows noticeable discrepancies in the building area. However, such discrepancies do not propagate to the downwind mountainous and sea areas, which the accuracies are quite satisfactory. Thus, the CALMET-RIMPUFF is capable for local-scale modeling at this site.

PM2.5 disrupts thyroid hormone homeostasis through activation of the hypothalamic-pituitary-thyroid (HPT) axis and induction of hepatic transthyretin in female rats 2.5.

Fine particulate matter (PM2.5), a ubiquitous environmental pollutant, has been indicated to affect thyroid hormone (TH) homeostasis in women, but the detailed mechanism behind this effect remains unclear. The objective of this study was to evaluate the roles of the hypothalamic-pituitary-thyroid (HPT) axis and hepatic transthyretin in the thyroid-disrupting effects of PM2.5. Sprague Dawley rats were treated with PM2.5 (0, 15 and 30 mg/kg) by passive pulmonary inhalation for 49 days; and recovery experimental group rats were dosed with PM2.5 (30 mg/kg) for 35 days, and no treatment was done during the subsequent 14 days. PM2.5 was handled twice a day by passive pulmonary inhalation throughout the study. After treatment, pathological changes were analyzed by performing haemotoxylin and eosin staining, measuring levels of THs and urine iodine (UI) in serum, plasma, and urine samples using enzyme-linked immunoabsorbent assay, and expression of proteins in the hypothalamus, pituitary, thyroid, and liver tissues of rats were analyzed by immunohistochemistry and Western blotting. The levels of oxidative stress factors, such as reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (Gpx), and nuclear factor-kappa B (NF-κB) in female rats' plasma were also evaluated by ELISA. The results of these analyses revealed that PM2.5 treatment induced pathologic changes in rat thyroid and liver characterized by increased follicular cavity size and decreased amounts of follicular epithelial cells and fat vacuoles, respectively. Serum levels of triiodothyronine, thyroxine, and thyroid stimulating hormone were significantly decreased, plasma NF-κB level was increased and plasma redox state was unbalanced (enhanced ROS, MDA and Gpx levels; reduced SOD activities) in female rats treated with PM2.5 (P < 0.05). PM2.5 treatment suppressed the biosynthesis and biotransformation of THs by increasing sodium iodide symporter, thyroid transcription factor 1, thyroid transcription factor 2, and paired box 8 protein expression levels (P < 0.05). Additionally, thyroid stimulating hormone receptor and thyroid peroxidase levels were significantly decreased (P < 0.05). Both thyrotropin releasing hormone receptor and thyroid stimulating hormone beta levels were enhanced (P < 0.05). Moreover, transport of THs was inhibited due to reduced protein expression of hepatic transthyretin upon treatment with PM2.5. In summary, PM2.5 treatment could perturb TH homeostasis by affecting TH biosynthesis, biotransformation, and transport, affecting TH receptor levels, and inducing oxidative stress and inflammatory responses. Activation of the HPT axis and altered hepatic transthyretin levels therefore appear to play a crucial role in PM2.5-induced thyroid dysfunction.

A projection from the paraventricular nucleus of the thalamus to the shell of the nucleus accumbens contributes to footshock stress-induced social avoidance.

The paraventricular nucleus of the thalamus (PVT) is an area of the dorsal midline thalamus that contributes to footshock induced anxiety. The PVT sends a dense projection to the shell of the nucleus accumbens (NAcSh) and the present study explored if this projection is involved in the behavioral changes produced by a single exposure of rats to inescapable footshocks. The inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) hM4Di was transduced in PVT neurons that project to the NAcSh. Rats were exposed to an episode of moderately intense footshock (1.5 mA × 2 s × 5) and assigned to either high-responder (HR) or low-responder groups (LR) according to their level of fear generalization 24 h later. The effect of chemogenetic inhibition of the PVT-NAcSh projection on anxiety- and fear-like behaviors was assessed at approximately 2 weeks post-footshock. HR showed a higher level of social avoidance compared to non-shocked animals and LR. The elevated level of social avoidance was attenuated in the HR treated with the hM4Di agonist clozapine (0.01 mg/kg, i.p.) or clozapine N-oxide (CNO) administrations in the NAcSh while avoidance of open spaces and contextual fear expression were not affected. Analysis of protein product of the early to immediate gene cfos indicated that these effects were mediated by dynorphin neurons in the NAcSh. This study provides evidence for a role of a projection from the PVT to the NAcSh in stress-induced social avoidance independent of anxiety to non-social stimuli and contextual fear mechanisms.

Validation and sensitivity study of Micro-SWIFT SPRAY against wind tunnel experiments for air dispersion modeling with both heterogeneous topography and complex building layouts.

Micro-SWIFT SPRAY (MSS) is a 3D Lagrangian particle dispersion model that maintains a good balance between accuracy and computational cost. However, its capabilities for air dispersion modeling in the presence of both complex topography and high building densities have not been investigated for nuclear emergency response. In this study, MSS is systematically evaluated against two wind tunnel experiments that simulate a typical Chinese nuclear power plant with the above two features. The MSS predictions are compared with both 2D horizontal and vertical measurements. Sensitivity studies are performed with respect to the particle number, the lower bound of the turbulence intensity, and the horizontal and vertical grid size. The results demonstrate that ground-level predictions of both wind and radionuclide concentrations are in satisfactory agreement with the measurements under optimized parameter values. The vertical predictions exhibit site-dependent accuracy, but generally consistent tendencies. The default lower bound of the turbulence intensity in MSS may be insufficient for reproducing the correct plume width observed in the wind tunnel experiments. An increased lower bound is suggested to solve this problem. In addition, artificially high concentrations may arise near steep slopes if large horizontal/vertical grid sizes are used. Suitable parameters for preventing this problem are also provided.

Evaluation of Gas Explosion Injury Based on Analysis of Rat Serum Profile by Ultra-Performance Liquid Chromatography/Mass Spectrometry-Based Metabonomics Techniques.

Gas explosion can lead to serious global public health issues. Early period gas explosion injury (GEI) can induce a series of histopathologic and specific metabolic changes. Unfortunately, it is difficult to treat GEI thoroughly. To date, the specific molecular mechanism of GEI is still unclear. To accurately diagnose and provide comprehensive clinical intervention, we performed a global analysis of metabolic alterations involved in GEI. The physiological and behavioral indicators' changes of rats after gas explosion were observed. These metabolic alterations were first investigated in a rat model using serum metabonomics techniques and multivariate statistical analysis. Significant heart rate (HR), mean blood pressure (mBP), and neurobehavioral index changes were observed in the GEI group after gas explosion. UPLC-MS revealed evident separated clustering between the control and GEI groups using supervised partial least squares discriminant analysis (PLS-DA). We designed an integrated metabonomics study for identifying reliable biomarkers of GEI using a time-course analysis of discriminating metabolites in this experiment. The metabonomics analysis showed alterations in a number of biomarkers (21 from serum). The meaningful biomarkers of GEI provide new insights into the pathophysiological changes and molecular mechanisms of GEI, including the disturbances in oxidative stress and neuroinflammatory reaction, as well as in metabolism of lipids, glucose, and amino acids in rats, suggesting that the process of GEI in humans is likely to be comprehensive and dynamic. Correlations between the GEI group and the biomarkers identified from the rat model will be further explored to elucidate the metabolic pathways responsible for GEI in the human body.