Background Increasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the micro-structural changes in the central nervous system after infection. We aimed to identify the existence of potential brain micro-structural changes related to SARS-CoV-2. Methods In this prospective study, diffusion tensor imaging (DTI) and 3D high-resolution T1WI sequences were acquired in 60 recovered COVID-19 patients (56.67% male; age: 44.10 ± 16.00) and 39 age- and sex-matched non-COVID-19 controls (56.41% male; age: 45.88 ± 13.90). Registered fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were quantified for DTI, and an index score system was introduced. Regional volumes derived from Voxel-based Morphometry (VBM) and DTI metrics were compared using analysis of covariance (ANCOVA). Two sample t-test and Spearman correlation were conducted to assess the relationships among imaging indices, index scores and clinical information. Findings In this follow-up stage, neurological symptoms were presented in 55% COVID-19 patients. COVID-19 patients had statistically significantly higher bilateral gray matter volumes (GMV) in olfactory cortices, hippocampi, insulas, left Rolandic operculum, left Heschl's gyrus and right cingulate gyrus and a general decline of MD, AD, RD accompanied with an increase of FA in white matter, especially AD in the right CR, EC and SFF, and MD in SFF compared with non-COVID-19 volunteers (corrected p value <0.05). Global GMV, GMVs in left Rolandic operculum, right cingulate, bilateral hippocampi, left Heschl's gyrus, and Global MD of WM were found to correlate with memory loss ( p value <0.05). GMVs in the right cingulate gyrus and left hippocampus were related to smell loss ( p value <0.05). MD-GM score, global GMV, and GMV in right cingulate gyrus were correlated with LDH level ( p value <0.05). Interpretation Study findings revealed possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting the long-term consequences of SARS-CoV-2. Funding Shanghai Natural Science Foundation, Youth Program of National Natural Science Foundation of China, Shanghai Sailing Program, Shanghai Science and Technology Development, Shanghai Municipal Science and Technology Major Project and ZJ Lab.
The transcription factor hypoxia-inducible factor-1␣ (HIF-1␣) plays pivotal roles in physiology and pathophysiology. Constitutive or hypoxia-induced HIF-1␣ overexpression is observed in many types of cancers including prostate adenocarcinoma, in which it is associated with resistance to apoptosis and therapeutic agents. BCL-xL, a hypoxia-responsive, anti-apoptotic protein of the Bcl-2 family, is also overexpressed in prostate carcinoma and many other cancers. Despite this connection, whether BCL-xL expression is directly regulated by HIF-1␣ is not known. We used prostate cancer PC-3 cell with constitutive high HIF-1␣ level as a model to address this important question. We first generated prostate cancer PC-3 cells in which HIF-1␣ was stably knocked-down (HIF-KD) by using small interference RNA. BCL-xL was dramatically decreased in HIF-KD PC-3 cells, in parallel with sensitization to apoptosis with caspase-3 activation as well as decreased cell proliferation. We then demonstrated that HIF-1␣ directly regulated BCL-xL transcription by binding to a hypoxia-responsive element in the BCL-xL promoter (؊865 to ؊847) by reporter gene assay, chromatin immunoprecipitation, and electrophoretic mobility shift and supershift assays. HIF-1␣-dependent BCL-xL overexpression may be an important mechanism by which HIF-1␣ protects prostate cancer cells from apoptosis and leads to treatment resistance.
PIWI-interacting RNAs are a class of small RNAs that is most abundantly expressed in animal germline. Substantial research is going on to reveal the functions of piRNAs in the epigenetic and post-transcriptional regulation of transposons and genes. To collect and annotate these data, we developed piRBase, a database assisting piRNA functional study. Since its launch in 2014, piRBase has integrated 264 data sets from 21 organisms, and the number of collected piRNAs has reached 173 million. The latest piRBase release (v2.0, 2018) was more focused on the comprehensive annotation of piRNA sequences, as well as the increasing number of piRNAs. In addition, piRBase release v2.0 also contained the potential information of piRNA targets and disease related piRNA. All datasets in piRBase is free to access, and available for browse, search and bulk downloads at http://www.regulatoryrna.org/database/piRNA/.
ObjectiveTo investigate the role of quantitative analysis of T2 relaxation time in the magnetic resonance imaging (MRI) diagnosis of breast cancer.MethodsThe study enrolled patients with clinical breast masses who were examined using MRI at eight different echo times. The differences in T2 relaxation time of benign and malignant breast lesions were analysed.ResultsA total of 67 patients (67 breast lesions: 46 malignant, 21 benign) were examined. The mean ± SD T2 relaxation time was significantly lower in the 46 malignant lesions compared with the 21 benign lesions (82.69 ± 15.37 ms versus 95.48 ± 26.51 ms, respectively). The area under the curve was 0.731. Using 79.52 ms as the cut-off between benign and malignant breast lesions, a sensitivity of 85.7% and a specificity of 58.7% were obtained.ConclusionsThere was a significant difference in T2 relaxation time between benign and malignant breast lesions. The specificity of using T2 relaxation time alone for the differentiation of benign from malignant lesions was not high, but it could constitute a new adjunct in the MRI diagnosis of breast cancer.
BackgroundEnvironmental exposure to cadmium causes renal dysfunction and bone damage. Cadmium contamination in food is regarded as the main environmental source of non-occupational exposure. The aim of this study was to assess the contribution of dietary cadmium exposure in environmental cadmium exposure and its health risk among adults in Shanghai, China.MethodsA cross-sectional survey about food consumption was conducted in 2008 among 207 citizens aged over 40 years in Shanghai, China. The food frequency questionnaire was combined with food, tobacco and water cadmium exposure to estimate the daily environmental cadmium exposure in both point and probabilistic estimations. Urine and blood samples of the participants were analyzed for internal exposure to total cadmium. Correlation analysis was conducted between the internal cadmium exposure and environmental cadmium exposure.ResultsAccording to the point estimation, average daily environmental cadmium exposure of the participants was 16.7 μg/day and approached 33.8% of the provisional tolerable daily intake (PTDI). Dietary and tobacco cadmium exposure approached 25.8% and 7.9% of the PTDI, respectively. Males had higher levels of dietary cadmium exposure than females (p?=?0.002). The probabilistic model showed that 93.4% of the population did not have any health risks from dietary cadmium exposure. By sensitivity analysis, tobacco consumption, tobacco cadmium level, cadmium in vegetables and cadmium in rice accounted for 27.5%, 24.9%, 20.2% and 14.6% of the total cadmium exposure, respectively. The mean values of urinary and blood cadmium among the study population were 0.5 μg/L and 1.9 μg/L, respectively. Positive correlations were observed between environmental cadmium exposure and blood cadmium (R?=?0.52, P<0.01), tobacco cadmium intake and blood cadmium excluding non-smokers (R?=?0.26, P?=?0.049<0.05), and urine cadmium and age (R?=?0.15, P?=?0.037).ConclusionsIt has been suggested that there is no increased health risk among adult residents in Shanghai, China because of recent total cadmium exposure. Vegetables and rice were the main sources of dietary cadmium intake. Tobacco cadmium exposure, which accounted for approximately 25% of the total dietary cadmium exposure, was another important source of non-occupational cadmium exposure.
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