MRI of GlycoNOE in the human liver using GraspNOE-Dixon.

PURPOSE: The objective of this study was to develop a new MRI technique for non-invasive, free-breathing imaging of glycogen in the human liver using the nuclear Overhauser effect (NOE). METHODS: The proposed method, called GraspNOE-Dixon, uses a novel MRI sequence that combines steady-state saturation-transfer preparation with multi-echo golden-angle radial stack-of-stars sampling. Multi-echo acquisition enables fat/water-separated imaging for quantification of water-specific NOE. Image reconstruction is performed using the improved golden-angle radial sparse parallel imaging (GRASP-Pro) technique to exploit spatiotemporal correlations in dynamic images. To evaluate the proposed technique, imaging experiments were first performed on glycogen phantoms, followed by in vivo studies involving healthy volunteers and patients with fatty liver disease. In addition, a comparative assessment of signal changes before and after a 12-h fasting period was performed. RESULTS: Evaluation experiments on glycogen phantoms showed a robust linear correlation between the NOE signal and glycogen concentration. In vivo experiments demonstrated motion-robust NOE-weighted images, with potential for further acceleration. In subjects with varying liver fat content, the fat/water separation approach resulted in distortion-free Z-spectra, enabling the quantification of glycogen NOE. An approximately one-third reduction in the NOE signal was observed following a 12-h fasting period, consistent with a decrease in glycogen level. CONCLUSION: This study introduces a clinically feasible imaging technique, GraspNOE-Dixon, for free-breathing volumetric multi-echo imaging of hepatic glycogen at 3 T. The motion robust imaging technique developed here may also have applications in other body areas beyond liver imaging.

Free-breathing time-resolved 4D MRI with improved T1-weighting contrast.

This work proposes MP-Grasp4D (magnetization-prepared golden-angle radial sparse parallel 4D) MRI, a free-breathing, inversion recovery (IR)-prepared, time-resolved 4D MRI technique with improved T1-weighted contrast. MP-Grasp4D MRI acquisition incorporates IR preparation into a radial gradient echo sequence. MP-Grasp4D employs a golden-angle navi-stack-of-stars sampling scheme, where imaging data of rotating radial stacks and navigator stacks (acquired at a consistent rotation angle) are alternately acquired. The navigator stacks are used to estimate a temporal basis for low-rank subspace-constrained reconstruction. This allows for the simultaneous capture of both IR-induced contrast changes and respiratory motion. One temporal frame of the imaging volume in MP-Grasp4D MRI is reconstructed from a single stack and an adjacent navigator stack on average, resulting in a nominal temporal resolution of 0.16 seconds per volume. Images corresponding to the optimal inversion time (TI) can be retrospectively selected for providing the best image contrast. Reader studies were conducted to assess the performance of MP-Grasp4D MRI in liver imaging across 30 subjects in comparison with standard Grasp4D MRI without IR preparation. MP-Grasp4D MRI received significantly higher scores (P < 0.05) than Grasp4D in all assessment categories. There was a moderate to almost perfect agreement (kappa coefficient from 0.42 to 0.9) between the two readers for image quality assessment. When the scan time is reduced, MP-Grasp4D MRI preserves image contrast and quality, demonstrating additional acceleration capability. MP-Grasp4D MRI improves T1-weighted contrast for free-breathing time-resolved 4D MRI and eliminates the need for explicit motion compensation. This method is expected to be valuable in different MRI applications such as MR-guided radiotherapy.

DCE-MRI of the liver with sub-second temporal resolution using GRASP-Pro with navi-stack-of-stars sampling.

Respiratory motion-induced image blurring and artifacts can compromise image quality in dynamic contrast-enhanced MRI (DCE-MRI) of the liver. Despite remarkable advances in respiratory motion detection and compensation in past years, these techniques have not yet seen widespread clinical adoption. The accuracy of image-based motion detection can be especially compromised in the presence of contrast enhancement and/or in situations involving deep and/or irregular breathing patterns. This work proposes a framework that combines GRASP-Pro (Golden-angle RAdial Sparse Parallel MRI with imProved performance) MRI with a new radial sampling scheme called navi-stack-of-stars for free-breathing DCE-MRI of the liver without the need for explicit respiratory motion compensation. A prototype 3D golden-angle radial sequence with a navi-stack-of-stars sampling scheme that intermittently acquires a 2D navigator was implemented. Free-breathing DCE-MRI of the liver was conducted in 24 subjects at 3T including 17 volunteers and 7 patients. GRASP-Pro reconstruction was performed with a temporal resolution of 0.34-0.45 s per volume, whereas standard GRASP reconstruction was performed with a temporal resolution of 15 s per volume. Motion compensation was not performed in all image reconstruction tasks. Liver images in different contrast phases from both GRASP and GRASP-Pro reconstructions were visually scored by two experienced abdominal radiologists for comparison. The nonparametric paired two-tailed Wilcoxon signed-rank test was used to compare image quality scores, and the Cohen's kappa coefficient was calculated to evaluate the inter-reader agreement. GRASP-Pro MRI with sub-second temporal resolution consistently received significantly higher image quality scores (P < 0.05) than standard GRASP MRI throughout all contrast enhancement phases and across all assessment categories. There was a substantial inter-reader agreement for all assessment categories (ranging from 0.67 to 0.89). The proposed technique using GRASP-Pro reconstruction with navi-stack-of-stars sampling holds great promise for free-breathing DCE-MRI of the liver without respiratory motion compensation.

Disease trajectories before dementia: evidence from a large-scale community-based prospective study.

BACKGROUND: Systemic changes in multiple diseases may influence the onset of dementia. However, the specific temporality between exposure diseases and dementia remains uncertain. AIMS: By characterising the full spectrum of temporal disease trajectories before dementia, this study aims to yield a global picture of precursor diseases to dementia and to provide detailed instructions for risk management and primary prevention of dementia. METHOD: Using the multicentre, community-based prospective UK Biobank, we constructed disease trajectories before dementia utilising the phenome-wide association analysis, paired directional test and association quantification. Stratified disease trajectories were constructed by dementia subtypes, gender, age of diagnosis and Apolipoprotein E (ApoE) status, respectively. RESULTS: Our study population comprised 434 266 participants without baseline dementia and 4638 individuals with all-cause dementia. In total, 1253 diseases were extracted as potential components of the disease trajectory before dementia. We identified three clusters of disease trajectories preceding all-cause dementia, initiated by circulatory, metabolic and respiratory diseases occurring approximately 5-15 years before dementia. Cerebral infarction or chronic renal failure following chronic ischaemic heart disease was the specific trajectory before vascular dementia. Apolipoprotein E (ApoE) ε4 non-carriers exhibited more complex trajectories compared with carriers. Lipid metabolism disorders remained in the trajectories regardless of dementia subtypes, gender, age of diagnosis and ApoE status. CONCLUSIONS: This study provides a comprehensive view of the longitudinal disease trajectories before dementia and highlights the potential targets of midlife cardiometabolic dysfunction for dementia screening and prevention.

Disease trajectory of high neuroticism and the relevance to psychiatric disorders: A retro-prospective cohort study.

BACKGROUND: Neuroticism is a psychological personality trait that has a significant impact on public health and is also a potential predisposing factor for adverse disease outcomes; however, comprehensive studies of the subsequently developed conditions are lacking. The starting point of disease trajectory in terms of genetic variation remains unclear. METHOD: Our study included 344,609 adult participants from the UK Biobank cohort who were virtually followed up from January 1, 1997. Neuroticism levels were assessed using 12 items from the Eysenck Personality Questionnaire. We performed a phenome-wide association analysis of neuroticism and subsequent diseases. Binomial tests and logistic regression models were used to test the temporal directionality and association between disease pairs to construct disease trajectories. We also investigated the association between polygenic risk scores (PRSs) for five psychiatric traits and high neuroticism. RESULTS: The risk for 59 diseases was significantly associated with high neuroticism. Depression, anxiety, irritable bowel syndrome, migraine, spondylosis, and sleep disorders were the most likely to develop, with hazard ratios of 6.13, 3.66, 2.28, 1.74, 1.74, and 1.71, respectively. The disease trajectory network revealed two major disease clusters: cardiometabolic and chronic inflammatory diseases. Medium/high genetic risk groups stratified by the PRSs of four psychiatric traits were associated with an elevated risk of high neuroticism. We further identified eight complete phenotypic trajectory clusters of medium or high genetic risk for psychotic, anxiety-, depression-, and stress-related disorders. CONCLUSION: Neuroticism plays an important role in the development of somatic and mental disorders. The full picture of disease trajectories from the genetic risk of psychiatric traits and neuroticism in early life to a series of diseases later provides evidence for future research to explore the etiological mechanisms and precision management.

Rapid 3D T1 mapping using deep learning-assisted Look-Locker inversion recovery MRI.

PURPOSE: Conventional 3D Look-Locker inversion recovery (LLIR) T1 mapping requires multi-repetition data acquisition to reconstruct images at different inversion times for T1 fitting. To ensure B1 robustness, sufficient time of delay (TD) is needed between repetitions, which prolongs scan time. This work proposes a novel deep learning-assisted LLIR MRI approach for rapid 3D T1 mapping without TD. THEORY AND METHODS: The proposed approach is based on the fact that T 1 * $$ {\mathrm{T}}_1^{\ast } $$ , the effective T1 in LLIR imaging, is independent of TD and can be estimated from both LLIR imaging with and without TD, while accurate conversion of T 1 * $$ {\mathrm{T}}_1^{\ast } $$ to T1 requires TD. Therefore, deep learning can be used to learn the conversion of T 1 * $$ {\mathrm{T}}_1^{\ast } $$ to T1 , which eliminates the need for TD. This idea was implemented for inversion-recovery-prepared Golden-angel RAdial Sparse Parallel T1 mapping (GraspT1 ). 39 GraspT1 datasets with a TD of 6 s (GraspT1 -TD6) were used for training, which also incorporates additional anatomical images. The trained network was applied for T1 estimation in 14 GraspT1 datasets without TD (GraspT1 -TD0). The robustness of the trained network was also tested. RESULTS: Deep learning-based T1 estimation from GraspT1 -TD0 is accurate compared to the reference. Incorporation of additional anatomical images improves the accuracy of T1 estimation. The technique is also robust against slight variation in spatial resolution, imaging orientation and scanner platform. CONCLUSION: Our approach eliminates the need for TD in 3D LLIR imaging without affecting the T1 estimation accuracy. It represents a novel use of deep learning towards more efficient and robust 3D LLIR T1 mapping.

Evaluation of glymphatic-meningeal lymphatic system with intravenous gadolinium-based contrast-enhancement in cerebral small-vessel disease.

OBJECTIVE: To investigate the feasibility of using noninvasive neuroimaging methods in visualizing and evaluating the clearance of the glymphatic-meningeal lymphatic system (GMLS) in patients with arteriosclerotic cerebral small-vessel disease (CSVD) and controls. METHODS: This observational study recruited patients with high-burden CSVD and controls (age 50-80 years). At multiple time points before and after intravenous administration of a contrast agent, three-dimensional (3D) brain volume T1-weighted imaging and 3D Cube T2-fluid attenuated inversion recovery imaging were performed to visualize and assess the clearance of the glymphatics and meningeal lymphatic vessels (mLVs). We measured the signal intensity ratio (SIR) of four regions of interest representing the glymphatics and mLVs at each time point. The clearance rate at 24 h (CR24h) and changes in the SIR from baseline to 24 h (∆SIR) were defined as the clearance function. The analysis of variance was used to evaluate the group differences after adjusting for hypertension. RESULTS: A total of 20 CSVD patients and 15 controls were included. Cortical periarterial enhancement and the enhancement of enlarged perivascular spaces in the basal ganglia were respectively observed in 11 (55.00%) and 16 (80.00%) CSVD patients, but in none of controls. All CSVD patients and most of controls (80.00%) showed cortical perivenous enhancement. Para-sinus enhancement was observed in all participants. CSVD patients showed lower CR24h and higher ∆SIR of the glymphatics and mLVs (all p < 0.05). CONCLUSION: The impaired drainage of the GMLS in patients with high-burden CSVD could be visually evaluated using noninvasive neuroimaging methods with intravenous gadolinium-based contrast-enhancement. CLINICAL RELEVANCE STATEMENT: Dynamic intravenous contrast-enhanced MRI could visually evaluate the impaired drainage of the glymphatic-meningeal lymphatic system in patients with high-burden cerebral small-vessel disease and could help to explore a new therapeutic target. KEY POINTS: • Signal intensity changes in regions representing the glymphatic-meningeal lymphatic system (GMLS) can reflect the drainage function based on contrast-enhanced 3D-FLAIR and 3D T1-weighted MRI. • Impaired drainage of the GMLS in patients with high-burden CSVD can be visually evaluated using dynamic intravenous contrast-enhanced MRI. • This direct, noninvasive technique could serve as a basis for further GMLS studies and could help to explore a new therapeutic target in CSVD patients.

FBXW2 inhibits prostate cancer proliferation and metastasis via promoting EGFR ubiquitylation and degradation.

FBXW2 is a poorly characterized F-box protein, as a tumor suppressor that inhibits growth and metastasis of lung cancer by promoting ubiquitylation and degradation of oncogenic proteins, including SKP2 and ß-catenin. However, what the biological functions of FBXW2 in prostate cancer cells and whether FBXW2 targets other substrates to involve in progression of prostate cancer is still unclear. Here, we reported that overexpression of FBXW2 attenuated proliferation and metastasis of PCa models both in vitro and in vivo, while FBXW2 depletion exhibited the opposite effects. Intriguingly, FBXW2 was an E3 ligase for EGFR in prostate cancer. EGFR protein level and its half-life were extended by FBXW2 depletion, while EGFR protein level was decreased, and its half-life was shortened upon overexpression of FBXW2, but not its dominant-negative mutant. Importantly, FBXW2 bond to EGFR via its consensus degron motif (TSNNST), and ubiquitylated and degraded EGFR, resulting in repression of EGF function. Thus, our data uncover a novel that FBXW2 as a tumor suppressor of prostate cancer, inhibits EGFR downstream by promoting EGFR ubiquitination and degradation, resulting in repression of cell proliferation and metastasis.

Comparison of two techniques for the management of 2-3 cm lower pole renal calculi in obese patients.

OBJECTIVE: To compare the outcomes of mini percutaneous nephrolithotomy (mPNL) and retrograde intrarenal surgery (RIRS) for the management of 2-3 cm lower pole renal calculi (LPC) in obese patients. PATIENTS AND METHODS: 120 obese patients with 2-3 cm LPC were randomly divided into mPNL group and RIRS group. Demography, clinical characteristics, perioperative complications, and stone free rate (SFR) were recorded. Stone-free status means no stone on computed tomography 3 months after surgery, or residual fragments were less than 3 mm. RESULTS: Baseline characteristics were similar between the two groups. The mean stone burden was 585.39 ± 131.06 mm2 in the mPNL group and 548.64 ± 123.55 mm2 in the RIRS group (P = 0.125). The SFR of mPNL group was significantly better than that of RIRS group (86.2% vs 61.4%, P = 0.002). Besides, the overall complication rate was 22.4% in the mPNL group and 7% in the RIRS group (P = 0.02). Patients performed with mPNL required longer length of hospital stay than those with RIRS (P = 0.001). There were no significant differences in operative time and stone composition between the two groups. CONCLUSION: In our study, both mPNL and RIRS are safe and effective techniques for the treatment of 2-3 cm LPC in obese patients. Compared to RIRS, mPNL has better SFR at the expense of the higher incidence of complications and prolonged length of hospital stay.

Expression profiles, biological functions and clinical significance of circRNAs in bladder cancer.

Circular RNAs (circRNAs), which are single-stranded closed-loop RNA molecules lacking terminal 5' caps and 3' poly(A) tails, are attracting increasing scientific attention for their crucial regulatory roles in the occurrence and development of various diseases. With the rapid development of high-throughput sequencing technologies, increasing numbers of differentially expressed circRNAs have been identified in bladder cancer (BCa) via exploration of the expression profiles of BCa and normal tissues and cell lines. CircRNAs are critically involved in BCa biological behaviours, including cell proliferation, tumour growth suppression, cell cycle arrest, apoptosis, invasion, migration, metastasis, angiogenesis, and cisplatin chemoresistance. Most of the studied circRNAs in BCa regulate cancer biological behaviours via miRNA sponging regulatory mechanisms. CircRNAs have been reported to be significantly associated with many clinicopathologic characteristics of BCa, including tumour size, grade, differentiation, and stage; lymph node metastasis; tumour numbers; distant metastasis; invasion; and recurrence. Moreover, circRNA expression levels can be used to predict BCa patients' survival parameters, such as overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). The abundance, conservation, stability, specificity and detectability of circRNAs render them potential diagnostic and prognostic biomarkers for BCa. Additionally, circRNAs play crucial regulatory roles upstream of various signalling pathways related to BCa carcinogenesis and progression, reflecting their potential as therapeutic targets for BCa. Herein, we briefly summarize the expression profiles, biological functions and mechanisms of circRNAs and the potential clinical applications of these molecules for BCa diagnosis, prognosis, and targeted therapy.

Free-breathing abdominal T1 mapping using an optimized MR fingerprinting sequence.

In this work, we propose a free-breathing magnetic resonance fingerprinting (MRF) method that can be used to obtain B1+ -robust quantitative T1 maps of the abdomen in a clinically acceptable time. A three-dimensional MRF sequence with a radial stack-of-stars trajectory was implemented, and its k-space acquisition ordering was adjusted to improve motion-robustness in the context of MRF. The flip angle pattern was optimized using the Cramér-Rao Lower Bound, and the encoding efficiency of sequences with 300, 600, 900 and 1800 flip angles was evaluated. To validate the sequence, a movable multicompartment phantom was developed. Reference multiparametric maps were acquired under stationary conditions using a previously validated MRF method. Periodic motion of the phantom was used to investigate the motion-robustness of the proposed sequence. The best performing sequence length (600 flip angles) was used to image the abdomen during a free-breathing volunteer scan. When using a series of 600 or more flip angles, the estimated T1 values in the stationary phantom showed good agreement with the reference scan. Phantom experiments revealed that motion-related artifacts can appear in the quantitative maps and confirmed that a motion-robust k-space ordering is essential. The in vivo scan demonstrated that the proposed sequence can produce clean parameter maps while the subject breathes freely. Using this sequence, it is possible to generate B1+ -robust quantitative maps of T1 and B1+ next to M0 -weighted images under free-breathing conditions at a clinically usable resolution within 5 min.

Comparison of contrast-enhanced ultrasound versus conventional ultrasound-guided percutaneous nephrolithotomy in patients with nondilated collecting system: a randomized controlled trial.

OBJECTIVE: To compare the safety, effectiveness, and feasibility of contrast-enhanced ultrasound (CEUS) versus conventional ultrasound-guided percutaneous nephrolithotomy (PCNL) in patients with nondilated collecting system. METHODS: Between July 2018 and July 2020, 160 kidney stone patients with nondilated collecting system planned for PCNL were randomly assigned into two groups, CEUS with retrograde ureteral contrast injection and conventional ultrasound with retrograde ureteral normal saline injection. Patient's demographics, the success rate of puncture, success rate of a single-needle puncture, number of punctures, puncture time, perioperative outcomes, stone-free rate, and incidence of complications were compared. RESULTS: The success rate of a single-needle puncture for CEUS-guided PCNL was higher than that in the conventional ultrasound group (88.5% vs. 73.7%, p = 0.02). Patients performed with CEUS-guided PCNL required less needle passes (p = 0.02), shorter needle puncture time (p = 0.031), and shorter channel establishment time (p = 0.04) than those guided with conventional ultrasound. The postoperative hemoglobin decrease in the CEUS-guided PCNL group was less than that of the control group (p = 0.02). There was no significant difference in operating time, length of hospital stays, kidney function change, and complications between the two groups (p > 0.05). The 1-month stone-free rate was 94.9% in the CEUS group and 90.8% in the control group (p > 0.05). CONCLUSIONS: Compared with conventional ultrasound, CEUS-guided PCNL may facilitate ultrasound-guided PCNL for patients without hydronephrosis, and benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800016981 KEY POINTS: • Compared with conventional ultrasound, CEUS-guided PCNL is a safe and efficacious procedure for kidney stone patients with nondilated collecting system. • Compared with conventional ultrasound, CEUS-guided PCNL benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop. • CEUS-guided PCNL associated with the more accurate needle puncture and acceptable complications.

A Novel Model for Landslide Displacement Prediction Based on EDR Selection and Multi-Swarm Intelligence Optimization Algorithm.

With the widespread application of machine learning methods, the continuous improvement of forecast accuracy has become an important task, which is especially crucial for landslide displacement predictions. This study aimed to propose a novel prediction model to improve accuracy in landslide prediction, based on the combination of multiple new algorithms. The proposed new method includes three parts: data preparation, multi-swarm intelligence (MSI) optimization, and displacement prediction. In the data preparation, the complete ensemble empirical mode decomposition (CEEMD) is adopted to separate the trend and periodic displacements from the observed cumulative landslide displacement. The frequency component and residual component of reconstructed inducing factors that related to landslide movements are also extracted by the CEEMD and t-test, and then picked out with edit distance on real sequence (EDR) as input variables for the support vector regression (SVR) model. MSI optimization algorithms are used to optimize the SVR model in the MSI optimization; thus, six predictions models can be obtained that can be used in the displacement prediction part. Finally, the trend and periodic displacements are predicted by six optimized SVR models, respectively. The trend displacement and periodic displacement with the highest prediction accuracy are added and regarded as the final prediction result. The case study of the Shiliushubao landslide shows that the prediction results match the observed data well with an improvement in the aspect of average relative error, which indicates that the proposed model can predict landslide displacements with high precision, even when the displacements are characterized by stepped curves that under the influence of multiple time-varying factors.

Magnetization transfer in magnetic resonance fingerprinting.

PURPOSE: To study the effects of magnetization transfer (MT, in which a semi-solid spin pool interacts with the free pool), in the context of magnetic resonance fingerprinting (MRF). METHODS: Simulations and phantom experiments were performed to study the impact of MT on the MRF signal and its potential influence on T1 and T2 estimation. Subsequently, an MRF sequence implementing off-resonance MT pulses and a dictionary with an MT dimension, generated by incorporating a two-pool model, were used to estimate the fractional pool size in addition to the B1+ , T1 , and T2 values. The proposed method was evaluated in the human brain. RESULTS: Simulations and phantom experiments showed that an MRF signal obtained from a cross-linked bovine serum sample is influenced by MT. Using a dictionary based on an MT model, a better match between simulations and acquired MR signals can be obtained (NRMSE 1.3% vs. 4.7%). Adding off-resonance MT pulses can improve the differentiation of MT from T1 and T2 . In vivo results showed that MT affects the MRF signals from white matter (fractional pool-size ~16%) and gray matter (fractional pool-size ~10%). Furthermore, longer T1 (~1060 ms vs. ~860 ms) and T2 values (~47 ms vs. ~35 ms) can be observed in white matter if MT is accounted for. CONCLUSION: Our experiments demonstrated a potential influence of MT on the quantification of T1 and T2 with MRF. A model that encompasses MT effects can improve the accuracy of estimated relaxation parameters and allows quantification of the fractional pool size.

A Hybrid Landslide Displacement Prediction Method Based on CEEMD and DTW-ACO-SVR-Cases Studied in the Three Gorges Reservoir Area.

Accurately predicting the surface displacement of the landslide is important and necessary. However, most of the existing research has ignored the frequency component of inducing factors and how it affects the landslide deformation. Therefore, a hybrid displacement prediction model based on time series theory and various intelligent algorithms was proposed in this paper to study the effect of frequency components. Firstly, the monitoring displacement of landslide from the Three Gorges Reservoir area (TGRA) was decomposed into the trend and periodic components by complete ensemble empirical mode decomposition (CEEMD). The trend component can be predicted by the least square method. Then, time series of inducing factors like rainfall and reservoir level was reconstructed into high frequency components and low frequency components with CEEMD and t-test, respectively. The dominant factors were selected by the method of dynamic time warping (DTW) from the frequency components and other common factors (e.g., current monthly rainfall). Finally, the ant colony optimization-based support vector machine regression (ACO-SVR) is utilized for prediction purposes in the TGRA. The results demonstrate that after considering the frequency components of landslide-induced factors, the accuracy of the displacement prediction model based on ACO-SVR is better than that of other models based on SVR and GA-SVR.

Experimental Investigation of the Physical Properties and Microstructure of Slate under Wetting and Drying Cycles Using Micro-CT and Ultrasonic Wave Velocity Tests.

Cyclic wetting and drying processes have been considered as important factors that accelerate the weathering process and have deteriorative effects on rock properties. In the present study, a fully nondestructive and noninvasive testing approach utilizing micro-CT and ultrasonic wave velocity tests was employed to investigate the microstructure of slate under wetting and drying cycles. We studied variations in the physical properties, including the dry weight and the velocities of P- and S-waves versus the number of wetting and drying cycles. The internal microstructural distributions were visualized and quantified by the 3D reconstruction and hybrid image segmentation of CT images. The degree of deterioration caused by wetting and drying cycles was reflected by exponential decreases of physical properties, including dry weight and velocities of the P- and S-waves. Parameters relating to the microfracture diameter, volume, etc. were quantified. The nondestructive and noninvasive testing approach utilizing micro-CT and ultrasonic wave velocity tests has potential for the detection and visualization of the internal microstructure of rock under wetting and drying cycles.

Calcium-activated nucleotidase 1 silencing inhibits proliferation, migration, and invasion in human clear cell renal cell carcinoma.

Calcium-activated nucleotidase 1 (CANT1, belongs to the apyrase family, is widely expressed in various organs. However, the biological function of CANT1 remains poorly explored. In this study, we aimed to investigate the expression profile and functions of CANT1 in clear cell renal cell carcinoma (ccRCC). Our data show that the protein level of CANT1 was significantly higher in tumor tissues than in adjacent normal tissues. CANT1 silencing suppressed cell proliferation, migration, and invasion obviously in 769-P and 786-O cells, arrested cell cycle in S phase and promoted apoptosis in 769-P cells. In conclusion, the present study shows the different expression mode of CANT1 in human ccRCC tumor tissue and adjacent normal tissue, denotes the function of CANT1 in ccRCC cells and provides potential molecular mechanisms and pathways of CANT1 antitumor function in ccRCC.

MicroRNA-34a Attenuates Paclitaxel Resistance in Prostate Cancer Cells via Direct Suppression of JAG1/Notch1 Axis.

BACKGROUND/AIMS: Treatment options for metastatic castrate-resistant prostate cancer (mCRPC) are limited and typically centered on paclitaxel-based chemotherapy. In this study, we aimed to evaluate whether miR-34a attenuates chemoresistance to paclitaxel by regulating target genes associated with drug resistance. METHODS: We used data from The Cancer Genome Atlas to compare miR-34a expression levels in prostate cancer (PC) tissues with normal prostate tissues. The effects of miR-34a inhibition and overexpression on PC proliferation were evaluated in vitro via Cell Counting Kit-8 (CCK-8) proliferation, colony formation, apoptosis, and cell-cycle assays. A luciferase reporter assay was employed to identify the interactions between miR-34a and specific target genes. To determine the effects of up-regulation of miR-34a on tumor growth and chemo-resistance in vivo, we injected PC cells overexpressing miR-34a into nude mice subcutaneously and evaluated the rate of tumor growth during paclitaxel treatment. We examined changes in the expression levels of miR-34a target genes JAG1 and Notch1 and their downstream genes via miR-34a transfection by quantitative reverse transcription PCR (qRT-PCR) and western blot assay. RESULTS: miR-34a served as an independent predictor of reduced patient survival. MiR-34a was down-regulated in PC-3PR cells compared with PC-3 cells. The CCK-8 assay showed that miR-34a overexpression resulted in increased sensitivity to paclitaxel while miR-34a down-regulation resulted in chemoresistance to paclitaxel in vitro. A study of gain and loss in a series of functional assays revealed that PC cells expressing miR-34a were chemosensitive. Furthermore, the overexpression of miR-34a increased the sensitivity of PC-3PR cells to chemotherapy in vivo. The luciferase reporter assay confirmed that JAG1 and Notch1 were directly targeted by miR-34a. Interestingly, western blot analysis and qRT-PCR confirmed that miR-34a inhibited the Notch1 signaling pathway. We found that miR-34a increased the chemosensitivity of PC-3PR cells by directly repressing the TCF1/ LEF1 axis. CONCLUSION: Our results showed that miR-34a is involved in the development of chemosensitivity to paclitaxel. By regulating the JAG1/Notch1 axis, miR-34a or its target genes JAG1 or Notch1 might serve as potential predictive biomarkers of response to paclitaxel-based chemotherapy and/or therapeutic targets that will help to overcome chemoresistance at the mCRPC stage.

Quadrupolar jump-and-return pulse sequence for fluid-suppressed sodium MRI of the knee joint at 7T.

PURPOSE: To demonstrate the feasibility of the so-called quadrupolar jump-and-return (QJR) pulse sequence by assessing its performance on the contrast modification to knee cartilage and quality of fluid suppression in the knee joint in vivo at 7T. METHODS: The right knee joints of five healthy volunteers (3 males: mean age = 32.4 ± 1.3 years; 2 females: mean age = 27.9 ± 1.0 years; mean age = 30.6 ± 2.7 years) were scanned on a 7T scanner with variation of the delay in the QJR sequence from 1 ms to 5 ms. For one healthy volunteer, the QJR scan with the delay of 3 ms and the inversion-recovery (IR) scan were performed. Numerical simulations were conducted to evaluate the effects of B0 - and B1 -field inhomogeneities and residual quadrupolar couplings on fluid suppression and tissue contrast, respectively. RESULTS: The QJR sequence suppressed the fluid signal from the artery and produced the contrast of knee cartilage in vivo. Its performance was comparable to that of the conventional IR sequence. Numerical simulations suggested that the fluid suppression may not be affected much by field inhomogeneities but that a distribution of residual quadrupolar couplings and weak RF pulses may interfere with the clear interpretation of cartilage contrast. CONCLUSION: This preliminary work demonstrated that the QJR pulse sequence produces contrast for knee cartilage while suppressing the fluid signal from the artery. The knee cartilage contrast and quality of fluid suppression obtained from the QJR sequence were comparable to those of the IR sequence. Magn Reson Med 80:641-647, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Longitudinal study of sodium MRI of articular cartilage in patients with knee osteoarthritis: initial experience with 16-month follow-up.

OBJECTIVES: To evaluate the potential of sodium MRI to detect changes over time of apparent sodium concentration (ASC) in articular cartilage in patients with knee osteoarthritis (OA). METHODS: The cartilage of 12 patients with knee OA were scanned twice over a period of approximately 16 months with two sodium MRI sequences at 7 T: without fluid suppression (radial 3D) and with fluid suppression by adiabatic inversion recovery (IR). Changes between baseline and follow-up of mean and standard deviation of ASC (in mM), and their rate of change (in mM/day), were measured in the patellar, femorotibial medial and lateral cartilage regions for each subject. A matched-pair Wilcoxon signed rank test was used to assess significance of the changes. RESULTS: Changes in mean and in standard deviation of ASC, and in their respective rate of change over time, were only statistically different when data was acquired with the fluid-suppressed sequence. A significant decrease (p = 0.001) of approximately 70 mM in mean ASC was measured between the two IR scans. CONCLUSION: Quantitative sodium MRI with fluid suppression by adiabatic IR at 7 T has the potential to detect a decrease of ASC over time in articular cartilage of patients with knee osteoarthritis. KEY POINTS: • Sodium MRI can detect apparent sodium concentration (ASC) in cartilage • Longitudinal study: sodium MRI can detect changes in ASC over time • Potential for follow-up studies of cartilage degradation in knee osteoarthritis.