Preparation for mice spaceflight: Indications for training C57BL/6J mice to adapt to microgravity effect with three-dimensional clinostat on the ground.

Like astronauts, animals need to undergo training and screening before entering space. At present, pre-launch training for mice mainly focuses on adaptation to habitat system. Training for the weightless environment of space in mice has not received much attention. Three-dimensional (3D) clinostat is a method to simulate the effects of microgravity on Earth. However, few studies have used a 3D clinostat apparatus to simulate the effects of microgravity on animal models. Therefore, we conducted a study to evaluate the feasibility and effects of long-term treatment with three-dimensional clinostat in C57BL/6 J mice. Thirty 8-week-old male C57BL/6 J mice were randomly assigned to three groups: mice in individually ventilated cages (MC group, n = 6), mice in survival boxes (SB group, n = 12), and mice in survival boxes receiving 3D clinostat treatment (CS group, n = 12). The mice showed good tolerance after 12 weeks of alternate day training. To evaluate the biological effects of simulated microgravity, the changes in serum metabolites were monitored using untargeted metabolomics, whereas bone loss was assessed using microcomputed tomography of the left femur. Compared with the metabolome of the SB group, the metabolome of the CS group showed significant differences during the first three weeks and the last three weeks. The KEGG pathways in the late stages were mainly related to the nervous system, indicating the influence of long-term microgravity on the central nervous system. Besides, a marked reduction in the trabecular number (P < 0.05) and an increasing trend of trabecular spacing (P < 0.1) were observed to occur in a time-dependent manner in the CS group compared with the SB group. These results showed that mice tolerated well in a 3D clinostat and may provide a new strategy in pre-launch training for mice and conducting relevant ground-based modeling experiments.

PM2.5 exposure promotes asthma in aged Brown-Norway rats: Implication of multiomics analysis.

Children are disproportionately represented among those who suffer asthma, which is a kind of chronic airway inflammation. Asthma symptoms might worsen when exposed to the air pollutant particulate matter 2.5 (PM2.5). However, it is becoming more prevalent among older adults, with more asthma-related deaths occurring in this pollution than in any other age group, and symptoms caused by asthma can reduce the quality of life of the elderly, whose asthma is underdiagnosed due to physiological factors. Therefore, in an effort to discover a therapy for older asthma during exposure to air pollution, we sought to ascertain the effects of pre-exposure (PA) and persistent exposure (PAP) to PM2.5 in aged asthma rats. In this study, we exposed aged rats to PM2.5 at different times (PA and PAP) and established an ovalbumin-mediated allergic asthma model. The basic process of elderly asthma caused by PM2.5 exposure was investigated by lung function detection, enzyme-linked immunosorbent assay (ELISA), histopathology, cytology, cytokine microarray, untargeted metabolomics, and gut microbiota analysis. Our findings demonstrated that in the PA and PAP groups, exposure to PM2.5 reduced lung function and exacerbated lung tissue damage, with varying degrees of effect on immunoglobulin levels, the findings of a cytological analysis, cytokines, and chemokines. The PA and PAP rats had higher amounts of polycyclic aromatic hydrocarbons (PAHs), such as naphthalene, 2-methylNaphthalene, 1-methylNaphthalene and flourene. Moreover, exposure to PM2.5 at different times showed different effects on plasma metabolism and gut microbiota. Bioinformatics analysis showed a strong correlation between PAHs, cytokines, and gut microbiota, and PAHs may cause metabolic disorders through the gut microbiota. These findings point to a possible mechanism for the development of asthma in older people exposure to PM2.5 that may be related to past interactions between PAHs, cytokines, gut microbiota, and plasma metabolites.

Radiomics Signatures of Carotid Plaque on Computed Tomography Angiography : An Approach to Identify Symptomatic Plaques.

PURPOSE: To develop and validate a combined model incorporating conventional clinical and imaging characteristics and radiomics signatures based on head and neck computed tomography angiography (CTA) to assess plaque vulnerability. METHODS: We retrospectively analyzed 167 patients with carotid atherosclerosis who underwent head and neck CTA and brain magnetic resonance imaging (MRI) within 1 month. Clinical risk factors and conventional plaque characteristics were evaluated, and radiomic features were extracted from the carotid plaques. The conventional, radiomics and combined models were developed using fivefold cross-validation. Model performance was evaluated using receiver operating characteristic (ROC), calibration, and decision curve analyses. RESULTS: Patients were divided into symptomatic (n = 70) and asymptomatic (n = 97) groups based on MRI results. Homocysteine (odds ratio, OR 1.057; 95% confidence interval, CI 1.001-1.116), plaque ulceration (OR 6.106; 95% CI 1.933-19.287), and carotid rim sign (OR 3.285; 95% CI 1.203-8.969) were independently associated with symptomatic status and were used to construct the conventional model and s radiomic features were retained to establish the radiomics model. Radiomics scores incorporated with conventional characteristics were used to establish the combined model. The area under the ROC curve (AUC) of the combined model was 0.832, which outperformed the conventional (AUC = 0.767) and radiomics (AUC = 0.797) models. Calibration and decision curves analysis showed that the combined model was clinically useful. CONCLUSION: Radiomics signatures of carotid plaque on CTA can well predict plaque vulnerability, which may provide additional value to identify high-risk patients and improve outcomes.

The temporal characteristics of the disruption of gut microbiota, serum metabolome, and cytokines by silica exposure in wistar rats.

Silicosis is one of the most frequent, rapidly developing, and lethal types of pneumoconiosis. However, our understanding of the underlying mechanisms of its pathogenesis and progress remains unclear. We investigated the fundamental processes of silicosis incidence and progression using a combination of lung function testing, histopathology, 16 S rRNA, untargeted metabolomics, and cytokine chips at different exposure times (4 or 8 weeks). The results show that silica exposure damages lung tissue reduces lung function, and increases with time. Cytokines with time-specific properties were found in lung lavage fluid: IFN-γ (4 weeks; P＜0.05), TNF-α, M-CSF, GM-CSF (8 weeks; P＜0.01). In addition, silica exposure for different periods interferes to varying degrees with the metabolism of lipids. The composition of the intestinal microbiota changed with increasing exposure time and there were time-specific: Allobaculum, Turicibacter、Jeotgalicoccu、Coprococcus 1 (4 weeks; P＜0.05), Ruminococcaceae NK4A214 group、Ruminiclostridium 5 (8 weeks; P＜0.05). We found strong associations between cytokines, gut microbiota changes, and metabolic disturbances at different exposure times. These results suggest that time-specific changes in crosstalk among cytokines, the gut microbiota, and metabolites may be a potential mechanism for silica-induced lung injury.

Performance of Radiomics Models Based on Coronary Computed Tomography Angiography in Predicting The Risk of Major Adverse Cardiovascular Events Within 3 Years: A Comparison Between the Pericoronary Adipose Tissue Model and the Epicardial Adipose Tissue Model.

RATIONALE AND OBJECTIVES: To compare the prediction performance of the epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT) radiomics models based on coronary computed tomography angiography for major adverse cardiovascular events (MACE) within 3 years. MATERIALS AND METHODS: Our study included 288 patients (144 with MACE and 144 without MACE within 3 years) by matching age, gender, body mass index, and medication intake. Patients were randomly assigned either to the training (n = 201) or validation cohort (n = 87). A total of 184 radiomics features were extracted from EAT and PCAT images. Spearman's rank correlation coefficient and the gradient boosting decision tree algorithm were performed for feature selection. Five models were established based on PCAT or EAT radiomics features and clinical factors, including PCAT, EAT, clinical, PCAT-clinical, and EAT-clinical model (MPCAT, MEAT, Mclinical, MPCAT-clinical, and MEAT-clinical). Receiver operating characteristic curves, calibration curves, and the decision curve analysis were plotted to evaluate the model performance. RESULTS: The MPCAT achieved an area under the curve (AUC) of 0.703 in the validation cohort, which was better than MEAT with AUC of 0.538. The MPCAT-clinical showed better performance (AUC = 0.781) in predicting MACE than the Mclinical (AUC = 0.748) or MEAT-clinical (AUC = 0.745). CONCLUSION: Our results showed that the PCAT was better than the EAT in both single modality and combined models, and the MPCAT-clinical had the most significant clinical value in predicting the occurrence of MACE within 3 years.

Antitumor effect of resorcinol derivatives from the roots of Ardisia brevicaulis by inducing apoptosis.

Two new resorcinol derivatives 2-methoxy-4-hydroxy-6-(8Z-pentadecenyl)-benzene-1-O-acetate (1) and 2-methoxy-4-hydroxy-6-pentadecyl-benzene-1-O-acetate (2), together with four known compounds 2-methoxy-4-hydroxy-6-tridecyl-benzene-1-O-acetate (ardisiphenol D, 3), 5-(8Z-pentadecenyl)resorcinol (4), 5-pentadecylresorcinol (5), 5-tridecylresorcinol (6), have been isolated from the roots of Ardisia brevicaulis in our previous work. In the present study, the inhibitory effect of 1-6 on the proliferation of human pancreatic PANC-1, human lung A549, human gastrointestinal carcinoma SGC 7901, human breast MCF-7, and human prostate PC-3 cancer cells was evaluated by the methyl thiazolyl tetrazolium method. Compounds 1-6 all showed inhibitory activities against the proliferation of PANC-1, A549, SGC7901, MCF-7, and PC-3 cancer cells. Compound 3, the most active agent and the main constituent with the highest yield, induced apoptosis of PANC-1 cells (the most sensitive cell line among the cell lines screened) via the activation of caspase-3 and caspase-9, up-regulation of the ratio of bax/bcl-2 protein expression.

Residue dynamic of pyrimorph on tomatoes, cucumbers and soil under greenhouse trails.

A modified QuEChERS method for analysis of pyrimorph residue in tomatoes, cucumbers and soil was developed and validated. Residue dynamics and final residues in greenhouse vegetables and soil were studied. At fortification levels of 0.05, 0.1 and 1 mg kg(-1) in tomatoes, cucumbers and soil, the method got recoveries ranged from 86.1% to 99.3% with relative standard deviations of 1.0%-7.7%, in agreement with directives for method validation in residue analysis. The limit of determination in tomatoes, cucumbers and soil was 0.05 mg kg(-1). The proposed method was successfully employed for the determination of pyrimorph residue levels and dissipation rates in vegetables and soil. At six experimental sites, pyrimorph residues in tomatoes and cucumbers showed relatively fast dissipation rates, with half-lives of 5.8-7.7 days and 5.7-7.1 days respectively. Half-lives of pyrimorph in soil were 8.5-11.0 days. The final residues of pyrimorph in tomatoes ranged from 0.19 to 3.66 mg kg(-1), 0.18 to 4.35 mg kg(-1) in cucumbers and 0.22 to 16.5 mg kg(-1) in soil with pre-harvest interval of 3-7 days. 5 mg kg(-1) was proposed as the MRL of pyrimorph in tomatoes and cucumbers.