Deciphering the disturbance mechanism of BaP on the symbiosis of Montipora digitata via 4D-Proteomics approach.

The coral holobiont is mainly composed of coral polyps, zooxanthellae, and coral symbiotic microorganisms, which form the basis of coral reef ecosystems. In recent years, the severe degradation of coral reefs caused by climate warming and environmental pollution has aroused widespread concern. Benzo(a)pyrene (BaP) is a widely distributed pollutant in the environment. However, the underlying mechanisms of coral symbiosis destruction due to the stress of BaP are not well understood. In this study, diaPASEF proteomics and 16S rRNA amplicon pyrosequencing technology were used to reveal the effects of 50 µg/L BaP on Montipora digitate. Data analysis was performed from the perspective of the main symbionts of M. digitata (coral polyps, zooxanthellae, and coral symbiotic microorganisms). The results showed that BaP impaired cellular antioxidant capacity by disrupting the GSH/GSSG cycle, and sustained stress causes severe impairment of energy metabolism and protein degradation in coral polyps. In zooxanthellae, BaP downregulated the protein expression of SOD2 and mtHSP70, which then resulted in oxidative free radical accumulation and apoptosis. For coral symbiotic microorganisms, BaP altered the community structure of microorganisms and decreased immunity. Coral symbiotic microorganisms adapted to the stress of BaP by adjusting energy metabolism and enhancing extracellular electron transfer. BaP adversely affected the three main symbionts of M. digitata via different mechanisms. Decreased antioxidant capacity is a common cause of damages to coral polyps and zooxanthellae, whereas coral symbiotic microorganisms are able to appropriately adapt to oxidative stress. This study assessed the effects of BaP on corals from a symbiotic perspective, which is more comprehensive and reliable. At the same time, data from the study supports new directions for coral research and coral reef protection.

Comparison of permeabilities of eight different types of cytotoxic drugs to five gloves with different materials by LC-MS/MS methods to reduce occupational exposure of medical personnel.

PURPOSE: Occupational exposure is a long-standing public health concern, which has drawn more and more attention in recent years to the problem of how to carry out occupational protection effectively. Gloves are regarded as the most critical protective equipment for cytotoxic medications. However, there is still little research conducted on the protective performance of gloves made of different materials and the optimal glove combination for cytotoxic agents. METHODS: In this research, a specific instrument intended for glove permeation experiment was designed, with various methods of liquid chromatography-tandem mass spectrometry (LC-MS/MS) developed and validated. By using the specific instrument and LC-MS/MS methods, a study was conducted on the permeation ability of eight selected cytotoxic drugs (fluorouracil, epirubicin (EPI), docetaxel (DCT), methotrexate (MTX), cyclophosphamide (CTX), etoposide (ETP), vincristine sulfate (VCR), and cisplatin derivatives Pt-(DDTC)3) into five kinds of gloves (rubber (RB), nitrile (NT), chlorinated polyethylene (CPE), low-density polyethylene, and polyvinylchloride (PVC) resin) given different contact times. Then, the experimental data were analyzed through a generalized estimation equation and Pearson correlation analysis. RESULTS: The results show that within a short period of time (less than five minutes), ETP, CTX, fluorouracil, DCT, and cisplatin passed through five types of gloves but the level of MTX, VCR, and EPI permeation was minimal, despite the duration of contact between the three drugs and the gloves reaching as long as three hours. Furthermore, the permeation of DCT and ETP was found to be positively correlated with time. CONCLUSIONS: Chlorinated polyethylene and PVC resin perform well in protecting against most cytotoxic drugs and are recommendable for clinical practice. Due to the poor protective ability, RB gloves are not recommended for this purpose. Based on the performance of various gloves in offering protection, the protection grade of two gloves can be deduced. Chlorinated polyethylene + PVC resin, CPE + NT glove combination shows good protective performance against most target drugs and can be recommended for clinical practice.

Using amide proton transfer-weighted MRI to non-invasively differentiate mismatch repair deficient and proficient tumors in endometrioid endometrial adenocarcinoma.

OBJECTIVES: To investigate the utility of three-dimensional (3D) amide proton transfer-weighted (APTw) imaging to differentiate mismatch repair deficient (dMMR) and mismatch repair proficient (pMMR) tumors in endometrioid endometrial adenocarcinoma (EEA). METHODS: Forty-nine patients with EEA underwent T1-weighted imaging, T2-weighted imaging, 3D APTw imaging, and diffusion-weighted imaging at 3 T MRI. Image quality and measurement confidence of APTw images were evaluated on a 5-point Likert scale. APTw and apparent diffusion coefficient (ADC) values were calculated and compared between the dMMR and pMMR groups and among the three EEA histologic grades based on the Federation of Gynecology and Obstetrics (FIGO) grading system criteria. Student's t-test, analysis of variance with Scheffe post hoc test, and receiver operating characteristic analysis were performed. Statistical significance was set at p < 0.05. RESULTS: Thirty-five EEA patients (9 with dMMR tumors and 26 with pMMR tumors) with good image quality were enrolled in quantitative analysis. APTw values were significantly higher in the dMMR group than in the pMMR group (3.2 ± 0.3% and 2.8 ± 0.5%, respectively; p = 0.019). ADC values of the dMMR and pMMR groups were 0.874 ± 0.104 × 10-3 mm2/s and 0.903 ± 0.100 × 10-3 mm2/s, respectively. No significant between-group difference was noted (p = 0.476). No statistically significant differences were observed in APTw values or ADC values among the three histologic grades (p = 0.766 and p = 0.295, respectively). CONCLUSIONS: APTw values may be used as potential imaging markers to differentiate dMMR from pMMR tumors in EEA.

Identification of Key Genes and Pathways in Gefitinib-Resistant Lung Adenocarcinoma using Bioinformatics Analysis.

Gefitinib resistance is a serious threat in the treatment of patients with non-small cell lung cancer (NSCLC). Elucidating the underlying mechanisms and developing effective therapies to overcome gefitinib resistance is urgently needed. The differentially expressed genes (DEGs) were screened from the gene expression profile GSE122005 between gefitinib-sensitive and resistant samples. GO and KEGG analyses were performed with DAVID. The protein-protein interaction (PPI) network was established to visualize DEGs and screen hub genes. The functional roles of CCL20 in lung adenocarcinoma (LUAD) were examined using gene set enrichment analysis (GSEA). Functional analysis revealed that the DEGs were mainly concentrated in inflammatory, cell chemotaxis, and PI3K signal regulation. Ten hub genes were identified based on the PPI network. The survival analysis of the hub genes showed that CCL20 had a significant effect on the prognosis of LUAD patients. GSEA analysis showed that CCL20 high expression group was mainly enriched in cytokine-related signaling pathways. In conclusion, our analysis suggests that changes in inflammation and cytokine-related signaling pathways are closely related to gefitinib resistance in patients with lung cancer. The CCL20 gene may promote the formation of gefitinib resistance, which may serve as a new biomarker for predicting gefitinib resistance in patients with lung cancer.

Texture analysis based on quantitative magnetic resonance imaging to assess kidney function: a preliminary study.

BACKGROUND: Magnetic resonance imaging (MRI) has demonstrated its potential in the evaluation of renal function. Texture analysis (TA) is a novel technique to quantify tissue heterogeneity. We aim to investigate the feasibility of using TA based on the apparent diffusion coefficient (ADC), as well as T1 and T2 maps to evaluate renal function. METHODS: Patients with impaired renal function and subjects with a normal renal function who underwent renal diffusion weighted imaging (DWI), as well as T1 and T2 mapping at 3T, were prospectively enrolled. The participants were classified into four groups according to the estimated glomerular filtration rate (eGFR, mL/min/1.73 m2): normal (eGFR ≥90), mildly impaired (60≤ eGFR <90), moderately impaired (30≤ eGFR <60), and severely impaired (eGFR <30) renal function groups. Texture features quantified from the renal cortex or medulla were selected to build classifiers to discriminate different renal function groups by plotting receiver operating characteristic (ROC) curves and calculating the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: In total, 116 candidates were included (94 patients and 22 healthy volunteers, mean age 37.9±14.9 years). There were 46 participants in the normal renal function group, 14 in the mildly impaired renal function group, 27 in the moderately impaired renal function group, and 29 in the severely impaired renal function group. Texture features from the ADC and T1 maps exhibited a good correlation to eGFR. The AUC, sensitivity, specificity, PPV, and NPV to differentiate between the normal and impaired renal function groups were 0.835, 0.792, 0.867, 0.905, and 0.722, respectively; to differentiate between the mildly impaired and moderately impaired groups were 0.937, 0.889, 0.857, 0.923, and 0.800, respectively; and to differentiate between the moderately impaired and severely impaired groups was 0.940, 0.759, 0.889, 0.880, and 0.774, respectively. CONCLUSIONS: TA based on ADC and T1 maps is feasible for evaluating renal function with relatively good accuracy.

Three-dimensional turbo-spin-echo amide proton transfer-weighted and intravoxel incoherent motion MR imaging for type I endometrial carcinoma: Correlation with Ki-67 proliferation status.

BACKGROUND: To evaluate 3-dimensional amide proton transfer weighted (APTw) imaging for type I endometrial carcinoma (EC), and investigate correlations of Ki-67 labelling index with APTw and intravoxel incoherent motion (IVIM) imaging. METHODS: 54 consecutive patients suspected of endometrial lesions underwent pelvic APTw and IVIM imaging on a 3 T MR scanner. APTw values and IVIM-derived parameters (Dt, D*, f) were independently measured by two radiologists on 22 postoperative pathological confirmed of type I EC lesions. Results were compared between histological grades and Ki-67 proliferation groups. ROC analysis was performed. Pearson's correlation analysis was performed for APTw values and IVIM-derived parameters with Ki-67 labeling index. RESULTS: APTw values and Dt, D*, f of all type I EC were 2.9 ± 0.1%, 0.677 ± 0.027 × 10-3 mm2/s, 31.801 ± 11.492 × 10-3 mm2/s, 0.179 ± 0.050 with inter-observer ICC 0.996, 0.850, 0.956, 0.995, respectively. APTw values of Ki-67 low-proliferation group (<30%, n = 8) were 2.5 ± 0.2%, significantly lower than the high-proliferation group (>30%, n = 14) with APTw values of 3.1 ± 0.1% (p = 0.016). Area under the curve was 0.768. APTw values of type I EC were moderately positively correlated with Ki-67 labelling index (r = 0.583, p = 0.004). There was no significant difference of Dt (p = 0.843), D* (p = 0.262), f (p = 0.553) between the two groups. No correlation was found between IVIM-derived parameters and Ki-67 labelling index (Dt, p = 0.717; D* p = 0.151; f, p = 0.153). CONCLUSION: 3D TSE APTw imaging is a feasible approach for detecting type I EC. Ki-67 labeling index positively moderately correlates with APTw not with IVIM.

Non-invasive Differentiation of Endometrial Adenocarcinoma from Benign Lesions in the Uterus by Utilization of Amide Proton Transfer-Weighted MRI.

PURPOSE: To evaluate the utility of three-dimensional (3D) amide proton transfer-weighted (APTw) imaging for differentiation of endometrial adenocarcinoma and uterine benign lesions. PROCEDURES: This prospective study enrolled 22 normal volunteers and 113 patients with suspicious uterine lesions, including endometrial adenocarcinoma, leiomyoma, and adenomyosis. Pelvic APTw MRI was performed on a 3-T MRI scanner with default APTw parameters. Two radiologists blindly evaluated uterine lesion APTw image quality by a 3-point Likert scale and independently measured APTw values on images with excellent to good image quality. Inter-reader agreement was evaluated. The Mann-Whitney U test with Bonferroni correction was used to compare the differences among different types of uterine lesions. A receiver operating characteristic analysis was performed. RESULTS: A total of 111 lesions (33 endometrial adenocarcinoma, 26 leiomyoma, and 52 adenomyosis lesions) from 99 patients revealing a majority of good quality with excellent inter-reader agreement were included for the image quality evaluation. APTw values of endometrial adenocarcinoma were 2.9 ± 0.1 %, significantly higher than those of leiomyoma (1.9 ± 0.1 %), adenomyosis (2.2 ± 0.1 %), and normal uterine myometrium (1.9 ± 0.1 %) (all p < 0.0001). The area under the receiver operating characteristic curve for differentiating endometrial adenocarcinoma from leiomyoma, adenomyosis, and myometrium was 0.87, 0.85, and 0.91, respectively. Feasible threshold APTw values of each group were determined as 2.4 %, 2.7 %, and 2.4 % with a sensitivity of 83.3 %, 76.7 %, and 83.3 % and a specificity of 83.3 %, 81.6 %, and 86.4 %, respectively. CONCLUSIONS: Malignant endometrial adenocarcinoma had significantly higher APTw values than leiomyoma, adenomyosis, and normal uterine myometrium. Our study adds to the growing body of validation on 3D APTw imaging and uterine lesions.

NPD1 inhibits excessive autophagy by targeting RNF146 and wnt/ß-catenin pathway in cerebral ischemia-reperfusion injury.

Objective: Cerebral ischemia-reperfusion (I/R) injury is a common pathological feature in ischemic stroke. Autophagy plays a key role in I/R-induced neuronal death. Neuroprotectin D1 (NPD1) is a docosahexaenoic acid derivative with neuroprotective and anti-inflammatory properties. The purpose of this study was to investigate the mediatory role of NPD1 on I/R-induced injury and to elucidate the underlying mechanisms involved in this process.Methods: An I/R injury model was established in PC12 cells induced by oxygen and glucose deprivation/reoxygenation (OGD/R). NPD1 at increasing doses (5, 10, 20, 50, 100 nM) were added to cells one hour before OGD/R. To investigate the effect of ring finger protein 146 (RFP146) deficiency in I/R injury, PC12 cells were transiently transfected with small interfering RNF146 before further experiment.Results: Compared to the controls, OGD/R-challenged cells exhibited significantly decreased cell viability, induced oxidative stress, and excessive autophagic cell death following OGD/R. Pretreatment with NPD1 protected cells against ischemic injury as evidenced by enhanced cell survival, decreased oxidative stress markers, and a lower level of autophagy compared to drug-free group. OGD/R also increased the level of RFP146 and inhibited the expression of ß-catenin in PC12 cells. NPD1 treatment promoted the production of RNF146 and ß-catenin in cells following OGD/R experiment. Moreover, RNF146 deficiency significantly inhibited ß-catenin expression and reversed the protective effects of NPD1 in OGD/R-induced cells.Conclusion: NPD1 alleviated excessive autophagy via regulating RNF146 and Wnt/ß-catenin signaling, suggesting the potential therapeutic use of NPD1 for the protection against cerebral I/R injury.

Diffusion-weighted imaging of cervical cancer: Feasibility of ultra-high b-value at 3T.

PURPOSE: We sought to evaluate the image quality and compare the signal intensity (SI) and apparent diffusion coefficient (ADC) maps of ultra-high b-value (2000 s/mm2; B2) images against those of 800 s/mm2 b-value (B1) images of diffusion-weighted imaging (DWI) for cervical cancer. METHOD: This study was approved by the institutional review board. Sixty patients diagnosed with cervical cancer by pathology were prospectively included. Female pelvic magnetic resonance imaging was performed using a 3 T magnetic resonance scanner; B1 and B2 images were obtained for evaluation. Two radiologists blinded to the scan parameters evaluated the images for signal loss in the background, spatial distortion, image ghosting, confidence in the lesion delineation, and overall image quality using a 5-point scoring system. The scores were compared using a paired Wilcoxon test. SI was measured in the B1 and B2 images for the tumour and normal reference tissues. Additionally, the SI contrast ratios were calculated and compared using the Mann-Whitney U test, the ADC values of tumours and normal tissues were measured, and the maximum tumour diameters were measured from the B1 and B2 images and compared with those from the T2-weighted images, which was the reference standard. RESULTS: The signal loss in the background, confidence of the lesion delineation and overall image quality scores were higher for the B2 images than for the B1 images (all p < 0.001). The contrast ratios of the tumour-to-normal SI were also higher for the B2 images than for the B1 images (p < 0.01). The mean ADC values derived from the B2 images showed better correlations with the tumour differentiation grades than those from the B1 images. The tumour diameters measured from the B2 images experienced less bias than those from the B1 images. CONCLUSIONS: B2 images of DWI are technically feasible to acquire and provide more promising additional information for the delineation of cervical cancer tumours than B1 images of the female pelvis.

Three-dimensional turbo-spin-echo amide proton transfer-weighted mri for cervical cancer: A preliminary study.

BACKGROUND: Amide proton transfer-weighted (APTw) imaging has shown great potential in the diagnosis of cancer, but has yet not been well studied in cervical cancer. PURPOSE: To evaluate the image quality and clinical feasibility of APTw MRI for cervical cancer. STUDY TYPE: Prospective. POPULATION: In all, 75 patients with cervical lesions and 49 healthy volunteers. FIELD STRENGTH/SEQUENCE: 3.0 T, 3D turbo spin echo (TSE) APTw sequence. ASSESSMENT: Three radiologists, blinded to the clinical data, independently evaluated APTw image quality with a 5-point Likert scale on 64 patients with pathologically confirmed cervical cancer. APT values, calculated based on asymmetry of acquired Z-spectrum with respect to water frequency, using 3D turbo spin echo volume acquisition with B0 correction, were independently measured by two radiologists, twice for each observer, on 52 cervical cancer lesions and 49 normal cervical stroma with a mean region of interest area of 638.6 mm2 and 557.5 mm2 , respectively. STATISTICAL TESTS: Interobserver agreement was evaluated by Kendall's W test. Intra- and interobserver interclass correlation coefficients (ICC) were computed. Student's t-test was used to compare the differences of APT values between cervical cancer and normal cervix; receiver operating characteristic analysis was performed. RESULTS: Most cases revealed good APTw image quality with excellent agreement (Kendall's W = 0.850, P < 0.001). APT values of cervical cancer and normal cervical stroma were 2.745 ± 0.065 and 1.853 ± 0.059, respectively, with a significant difference (P < 0.0001). Intraobserver ICCs were 0.963 and 0.960 for two readers. Interobserver ICC was 0.993. Area under the curve (AUC) for differentiating cervical cancer from normal cervical stroma was 0.927. The feasible threshold value for AUC was determined as 2.221 with sensitivity of 84.62% and specificity of 83.66%. DATA CONCLUSION: 3D TSE APTw MRI is feasible in cervical cancer. Cervical cancer showed significantly higher APT values than normal cervix. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1318-1325.

Bioinformatics analysis to identify the key genes affecting the progression and prognosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, which has poor outcome. The present study aimed to investigate the key genes implicated in the progression and prognosis of HCC. The RNA-sequencing data of HCC was extracted from The Cancer Genome Atlas (TCGA) database. Using the R package (DESeq), the differentially expressed genes (DEGs) were analyzed. Based on the Cluepedia plug-in in Cytoscape software, enrichment analysis for the protein-coding genes amongst the DEGs was conducted. Subsequently, protein-protein interaction (PPI) network was built by Cytoscape software. Using survival package, the genes that could distinguish the survival differences of the HCC samples were explored. Moreover, quantitative real-time reverse transcription-PCR (qRT-PCR) experiments were used to detect the expression of key genes. There were 2193 DEGs in HCC samples. For the protein-coding genes amongst the DEGs, multiple functional terms and pathways were enriched. In the PPI network, cyclin-dependent kinase 1 (CDK1), polo-like kinase 1 (PLK1), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), serum amyloid A1 (SAA1), and lysophosphatidic acid receptor 3 (LPAR3) were hub nodes. CDK1 interacting with PLK1 and FOS, and LPAR3 interacting with FOS and SAA1 were found in the PPI network. Amongst the 40 network modules, 4 modules were with scores not less than 10. Survival analysis showed that anterior gradient 2 (AGR2) and RLN3 could differentiate the high- and low-risk groups, which were confirmed by qRT-PCR. CDK1, PLK1, FOS, SAA1, and LPAR3 might be key genes affecting the progression of HCC. Besides, AGR2 and RLN3 might be implicated in the prognosis of HCC.

High expression of FAM13A was associated with increasing the liver cirrhosis risk.

AIM: Liver cirrhosis is a consequence of chronic liver disease, and it may be caused by multiple influences of both genetic and environmental factors. Family with sequence similarity 13 member A (FAM13A) has been previously associated with lung function in several lung diseases, including chronic obstructive pulmonary disease, asthma, lung cancer, and pulmonary fibrosis. The aim of this study was to explore whether FAM13A polymorphisms confer susceptibility to liver cirrhosis. METHODS: FAM13A expression was evaluated in liver cirrhosis tissues by immunohistochemistry staining. The relationship between FAM13A gene polymorphism and liver cirrhosis was determined by association analysis. The genotypes were assessed in the Agena MassARRAY platform. Statistical analysis was performed using chi-squared test/Fisher's exact test, genetic model analysis, and haplotype analysis. RESULTS: The results showed that the expression of FAM13A is obvious higher in the liver cirrhosis tissue cells than in the normal liver tissue cells. Moreover, association analysis results indicated that the minor allele "A" of rs3017895 was positively associated with high risk of liver cirrhosis in the allele model by the chi-squared test (OR = 1.32, 95%CI = 1.03-1.68, p = 0.028). Logistic regression analyses revealed that the risk of liver cirrhosis was significantly higher in subjects with the G/A-G/G genotype of rs3017895 than those with A/A genotype under the dominant model and log additive model, and the T/A-A/A genotype of rs1059122 was positively associated with higher liver cirrhosis than T/T genotype based on dominant model respectively. In addition, haplotype analysis showed that the G-A haplotype of rs3017895-rs1059122 of the FAM13A gene significantly increased the risk of liver cirrhosis. CONCLUSION: Our findings demonstrated that the high expression of FAM13A may be associated with an increased risk of liver cirrhosis.

Tissue-specific metabolic responses of the pearl oyster Pinctada martensii exposed to benzo[a]pyrene.

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) that is well known for its teratogenic, mutagenic and carcinogenic effects. In this study, we applied metabolomics to investigate the tissue-specific metabolic responses of the Pinctada martensii digestive glands and gills after a short-duration exposure to BaP (1 µg/L and 10 µg/L). After 72 h of exposure to BaP, the majority of metabolite changes were related to osmolytes, energy metabolites, and amino acids. BaP (1 µg/L) accelerated energy deterioration and decreased osmotic regulation, while BaP (10 µg/L) disturbed energy metabolism and increased osmotic stress in the digestive glands. Both BaP doses disturbed osmotic regulation and energy metabolism in the gills. BaP also induced neurotoxicity in both tissues. These findings demonstrated that BaP exhibited tissue-specific metabolic responses in P. martensii. The difference in these metabolite responses between the digestive glands and gills might prove to be suitable biomarkers for indicating exposure to specific marine pollutants.

An integrated metabolomic and proteomic study of toxic effects of Benzo[a]pyrene on gills of the pearl oyster Pinctada martensii.

Benzo[a]pyrene (BaP) is one of the most important polycyclic aromatic hydrocarbons (PAHs), which are widely present in the marine environment. Because of its teratogenic, mutagenic, and carcinogenic effects on various organisms, the toxicity of BaP is of great concern. In this study, we focused on the toxic effects of BaP (1 µg/L and 10 µg/L) on gills of the pearl oyster Pinctada martensii using combined metabolomic and proteomic approaches. At the metabolome level, the high concentration of BaP mainly caused abnormal energy metabolism, osmotic regulation and immune response marked by significantly altered metabolites in gills. At the proteome level, both concentrations of BaP mainly induced signal transduction, transcription regulation, cell growth, stress response, and energy metabolism. Overall, the research demonstrated that the combination of proteomic and metabolomic approaches could provide a significant way to elucidate toxic effects of BaP on P. martensii.

Etiology of intracranial stenosis in young patients: a high-resolution magnetic resonance imaging study.

BACKGROUND: Using high-resolution magnetic resonance imaging (HRMRI), we sought to investigate the underlying etiology of intracranial stenosis in young patients. METHODS: We retrospectively studied 122 Chinese young adult patients (from 18 to 45 years old, mean age 36.2±7.5 years) with unilateral middle cerebral artery (MCA) stenosis based on a prospectively established HRMRI database. The eccentricity, degree of stenosis, and remodeling types of MCA lesions were analyzed. The MCA lesions were classified as eccentric (presumed atherosclerosis) or concentric stenosis (presumed non-atherosclerosis). The clinical data and vessel wall properties were compared between the patients >35 years old and the patients ≤35 years old. RESULTS: Eccentric stenosis was observed in 98 (80.3%) patients and concentric stenosis in 24 (19.7%) patients. The patients with eccentric stenosis were older (37.5±6.8 vs. 31.4±8.4 years old, P<0.001) and more likely had atherosclerosis risk factors (56.1% vs. 25.0%, P=0.006). The patients >35 years old had higher prevalence (90.1% vs. 66.7%, P=0.001) of eccentric stenosis and atherosclerosis factors (60.6% vs. 35.3%, P=0.006) than the patients ≤35 years old. Most of the patients with concentric stenosis were ≤35 years old (17/24, 70.8%) and were female (16/24, 66.7%). Binary Logistic analysis suggested smoking (OR =3.171; 95% CI, 1.210-8.314) and remodeling ratio (OR =1.625; 95% CI, 1.001-2.636) were independent predictive factors for symptomatic stenosis. CONCLUSIONS: Atherosclerosis is the most common cause of intracranial stenosis in Chinese young patients. Non-atherosclerosis disease is an important etiology in young female, especially in the patients aged 35 years old or younger.

Dynamic responses of antioxidant enzymes in pearl oyster Pinctada martensii exposed to di(2-ethylhexyl) phthalate (DEHP).

Di(2-ethylhexyl) phthalate (DEHP) is recognized as one of the most ubiquitous contaminants in marine environments and causes adverse effects on the health of marine organisms. The purpose of this study was to investigate the toxic effects of DEHP on the pearl oyster Pinctada martensii. The Pinctada martensii was exposed to 0.0, 0.5, 2, 8, or 32mgL-1 DEHP for 7 and 10days using parameters of antioxidant. Antioxidant indicators included levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), peroxidase (POD), and total antioxidant capacity (T-AOC) in the gills and hepatopancreas of Pinctada martensii for 7 and 10days. Besides, we used the lowest observed effect concentration (LOEC) of five enzyme activities in different tissues of Pinctada martensii for 7 and 10days to compare sensitivity. The results showed that the gills were more sensitive than the hepatopancreas of Pinctada martensii and that GSH activity in the gills and CAT activity in the hepatopancreas might be suitable biomarkers after 7days of DEHP exposure. After 10days of DEHP exposure, the GSH activity and CAT activity in the gills and SOD activity in the hepatopancreas could be regarded as biomarkers. Compared to the LOEC, GSH activity in the gills and CAT activity in the hepatopancreas after 7days of DEHP exposure were more sensitive than any other biomarkers. In addition, after 10days of DEHP exposure, GSH activity in the gills and hepatopancreas were much more sensitive than other activities. In conclusion, GSH activity demonstrated its potential to be used as a biomarker for the monitoring of DEHP pollution in the marine environment.

The early-onset febrile reaction following vaccination and associated factors: An exploratory sub-study based on the Ebola vaccine clinical trial.

A phase-1 clinical trial aimed to assess the safety and immunogenicity of the type-5 adenovirus vector based Ebola vaccine (Ad5-EBOV) was conducted in China. To provide more evidence for the safety evaluation and dose-selection, an exploratory sub-study using a wireless automatic temperature measuring platform was done based on the phase-1 clinical trial. The main aim of the sub-study was to obtain more information about the occurrence of fever and detect the potential associated factors, second was to assess the feasibility of the temperature measuring platform in vaccine clinical trials. Temperature data of 3 treatment groups all presented a rising tendency during the first 6 hours after vaccination, the incidence of elevated temperature and possible associated factors were analyzed. For the incidence of elevated temperature, no marked dose-response relationship was found in 6 hours with wireless thermometers; the information from mercury thermometers showed that the grade-1 fever proportion peaked at 6 hours and there was no difference between groups, while grade-2 fever proportion peaked at 24 hours and was significantly higher in high-dose group than those in the other 2 groups. Significant differences were found between sex groups (males vs. female, incidence rate ratios (IRR) = 2.93 and 7.62 for any-grade, grade-2 fever respectively, P<0.001); a decline in grade-2 fever incidence was found with the increasing age groups (IRR = 0.78, P = 0.003) and body mass index (BMI, IRR = 0.67, P<0.001) .Our findings show that the dose-dependent manner between fever and the dose of Ad5-EBOV in this study might emerge after 6 hours, and which is slight and transient. Wireless thermometers secured on the skin surface are not suitable for a long time (longer than 6 hours) measurement, new methods for temperature monitoring, like ear temperature measurement, should be tested in the further research.

Transcriptomic responses of Perna viridis embryo to Benzo(a)pyrene exposure elucidated by RNA sequencing.

The green mussel Perna viridis is an ideal biomonitor to evaluate marine environmental pollution. Benzo(a)pyrene (BaP) is a typical polycyclic aromatic hydrocarbon (PAH), which is well known for the mutagenic and carcinogenic characteristics. However, the toxicological effects of BaP on Perna viridis embryo are still unclear. In this study, we investigated the embryo transcriptomic profile of Perna viridis treated with BaP via digital gene expression analysis. A total of 92,362,742 reads were produced from two groups (control and BaP exposure) by whole transcriptome sequencing (RNA-Seq). Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis were used on all genes to determine the biological functions and processes. Genes involved in various molecular pathways of toxicological effects were enriched further. The differential expression genes (DEGs) were related to stress response, infectious disease and innate immunity. Quantitative real-time PCR (qRT-PCR) measured expressional levels of six genes confirmed through the DGE analysis. This study reveals that RNA-seq for transcriptome profiling of P. viridis embryo can better understand the embryo toxic effects of BaP. Furthermore, it also suggests that RNA-seq is a superior tool for generating novel and valuable information for revealing the toxic effects caused by BaP at transcriptional level.

Proteomic and metabolomic analysis on the toxicological effects of Benzo[a]pyrene in pearl oyster Pinctada martensii.

Benzo[a]pyrene (BaP) is one of the typical toxic polycyclic aromatic hydrocarbons (PAHs) that are widely present in marine environment. BaP has diverse toxic effects, including teratogenic, carcinogenic, mutagenic effects and so on, in various organisms. In this work, we focused on the differential proteomic and metabolomic responses in the digestive gland of pearl oyster Pinctada martensii exposed to two doses of BaP (1 and 10µg/L). Metabolic responses revealed that the high dose of BaP (10µg/L) mainly caused disturbances in osmotic regulation and energy metabolism in the digestive gland. Proteomic responses indicated that both doses of BaP induced disturbances in energy metabolism, cytoskeleton, cell injury, oxidative stress and signal transduction based on the differential proteomic biomarkers. Overall, these results demonstrated a number of potential biomarkers that were characterized by an integrated proteomic and metabolomic approach and provided a useful insight into the toxicological effects on pearl oyster P. martensii.

Kynurenine aminotransferase 3/glutamine transaminase L/cysteine conjugate beta-lyase 2 is a major glutamine transaminase in the mouse kidney.

BACKGROUND: Kynurenine aminotransferase 3 (KAT3) catalyzes the transamination of Kynurenine to kynurenic acid, and is identical to cysteine conjugate beta-lyase 2 (CCBL2) and glutamine transaminase L (GTL). GTL was previously purified from the rat liver and considered as a liver type glutamine transaminase. However, because of the substrate overlap and high sequence similarity of KAT3 and KAT1, it was difficult to assay the specific activity of each KAT and to study the enzyme localization in animals. METHODS: KAT3 transcript and protein levels as well as enzyme activity in the liver and kidney were analyzed by regular reverse transcription-polymerase chain reaction (RT-PCR), real time RT-PCR, biochemical activity assays combined with a specific inhibition assay, and western blotting using a purified and a highly specific antibody, respectively. RESULTS: This study concerns the comparative biochemical characterization and localization of KAT 3 in the mouse. The results showed that KAT3 was present in both liver and kidney of the mouse, but was much more abundant in the kidney than in the liver. The mouse KAT3 is more efficient in transamination of glutamine with indo-3-pyruvate or oxaloacetate as amino group acceptor than the mouse KAT1. CONCLUSIONS: Mouse KAT3 is a major glutamine transaminase in the kidney although it was named a liver type transaminase. GENERAL SIGNIFICANCE: Our data highlights KAT3 as a key enzyme for studying the nephrotoxic mechanism of some xenobiotics and the formation of chemopreventive compounds in the mouse kidney. This suggests tissue localizations of KAT3/GTL/CCBL2 in other animals may be carefully checked.