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Abstract How brain functions in the distorted ischemic state before and after reperfusion is unclear. It is also uncertain whether there are any indicators within ischemic brain that could predict surgical outcomes. To alleviate these issues, we applied individual brain connectome in chronic steno‐occlusive vasculopathy (CSOV) to map both ischemic symptoms and their postbypass changes. A total of 499 bypasses in 455 CSOV patients were collected and followed up for 47.8 ± 20.5 months. Using multimodal parcellation with connectivity‐based and pathological distortion‐independent approach, areal MR features of brain connectome were generated with three measurements of functional connectivity (FC), structural connectivity, and PageRank centrality at the single‐subject level. Thirty‐three machine‐learning models were then trained with clinical and areal MR features to obtain acceptable classifiers for both ischemic symptoms and their postbypass changes, among which, 11 were deemed acceptable (AUC > 0.7). Notably, the FC feature‐based model for long‐term neurological outcomes performed very well (AUC > 0.8). Finally, a Shapley additive explanations plot was adopted to extract important individual features in acceptable models to generate “fingerprints” of brain connectome. This study not only establishes brain connectomic fingerprint databases for brain ischemia with distortion, but also provides informative insights for how brain functions before and after reperfusion.

Abstract Background and Aim Metabolic dysfunction‐associated steatotic liver disease (MASLD) is recently introduced to better highlight the pathogenic significance of cardiometabolic dysfunction, as compared with non‐alcoholic fatty liver disease. This study aimed to investigate the association between low thyroid function and MASLD in the new context. Methods We recruited 2901 participants for our retrospective cohort study from 2016 to 2021. Participants were divided into strict‐normal thyroid function and low thyroid function groups (low‐normal thyroid function, subclinical hypothyroidism) based on initial thyroid stimulating hormone (TSH) levels, respectively. Cox regression models were used to estimate the hazard ratios (HRs) and 95% CI. Results During a median follow‐up of 15.6 months, 165 (8.9%) strict‐normal thyroid function subjects and 141 (13.4%) low thyroid function subjects developed MASLD; this result was statistically relevant (P

Abstract The exact shape of intracranial aneurysms is critical in medical diagnosis and surgical planning. While voxel-based deep learning frameworks have been proposed for this segmentation task, their performance remains limited. In this study, we offer a two-step surface-based deep learning pipeline that achieves significantly better results. Our proposed model takes a surface model of an entire set of principal brain arteries containing aneurysms as input and returns aneurysm surfaces as output. A user first generates a surface model by manually specifying multiple thresholds for time-of-flight magnetic resonance angiography images. The system then samples small surface fragments from the entire set of brain arteries and classifies the surface fragments according to whether aneurysms are present using a point-based deep learning network (PointNet++). Finally, the system applies surface segmentation (SO-Net) to surface fragments containing aneurysms. We conduct a direct comparison of the segmentation performance of our proposed surface-based framework and an existing voxel-based method by counting voxels: our framework achieves a much higher Dice similarity (72%) than the prior approach (46%).

Rainfall and reservoir water level are commonly regarded as the two major influencing factors for reservoir landslides and are employed for landslide displacement prediction, yet their daily data are readily available with current monitoring technology, which makes a more refined analysis possible. However, until now, few efforts have been made to predict landslide displacements using daily data, which is likely to substantially improve accuracy and is crucial for landslide early warning. A novel feature enhancement approach for extracting critical characteristics from daily rainfall and reservoir water level data for use in landslide displacement prediction is proposed in this study. Six models, including gated recurrent units (GRUs), long short-term memory (LSTM), and support vector regression (SVR) with an unenhanced dataset and GRU-E, LSTM-E, and SVR-E with an enhanced dataset, were employed for displacement predictions at four GPS monitoring stations on the Baijiabao landslide, a typical step-like reservoir landslide. The results show that the accuracy values of all the enhanced models were significantly improved, and the GRU-E model achieved the most significant improvement, with the RMSE decreasing by 24.39% and R2 increasing by 0.2693, followed by the LSTM-E and SVR-E models. Further, the GRU-E model consistently outperformed the other models, achieving the highest R2 of 0.6265 and the lowest RMSE of 16.5208 mm, significantly superior than the others. This study indicates the feasibility of improving the accuracy of landslide monthly displacement predictions with finer monitoring data and provides valuable insights for future research.

Photothermal immunotherapy has drawn worldwide attentions for malignant tumors based on noninvasive methods of nanomaterials and immune-associated drugs in the past years. Photothermal immunotherapy performed excellent effects and less adverse reactions in the treatment of tumors compared with classical treatments including surgical removement, chemotherapy, radiotherapy, photothermal therapy (PTT), and photodynamic therapy (PDT) and single immunotherapy. Moreover, second near-infrared (NIR-Ⅱ) light performed more advantages in PTT/PDT and photoacoustic imaging than first near-infrared (NIR-Ⅰ) light. Photothermal immunotherapy with the irradiation of NIR-Ⅱ light can not only rapidly eliminate topical solid tumors located in deeper solid tumor tissue, but also it can trigger tumor-associated congenital and acquired immune responses which can prevent cancer local recurrence and distant metastasis. Photothermal immunotherapy under the NIR-Ⅱ light irradiation could be one of most essential and potential methods for cancer in the future. Therefore, we reviewed the related nanoparticles of photothermal immunotherapy with the irradiation of NIR Ⅱ window in cancer based on published articles in the study.

Circular RNAs (circRNAs) are covalently closed RNA molecules that play important regulatory roles in various tumors. Prostate cancer (PCa) is one of the most common malignant tumors in the world, with high morbidity and mortality. In recent years, more and more circRNAs have been found to be abnormally expressed and involved in the occurrence and development of PCa, including cell proliferation, apoptosis, invasion, migration, metastasis, chemotherapy resistance, and radiotherapy resistance. Most of the circRNAs regulate biological behaviors of cancer through a competitive endogenous RNA (ceRNA) regulatory mechanism, and some can exert their functions by binding to proteins. circRNAs are also associated with many clinicopathological features of PCa, including tumor grade, lymph node metastasis, and distant metastasis. In addition, circRNAs are potential diagnostic and prognostic biomarkers for PCa. Considering their critical regulatory roles in the progression of PCa, circRNAs would be the potential therapeutic targets. In this paper, the current research status of circRNAs in PCa is briefly reviewed.

ObjectiveThe aim of the current study was to evaluate the risk factors that influence the development of postoperative systemic inflammatory response syndrome (SIRS) after percutaneous nephrolithotomy (PCNL), including cytokines and lymphocyte subsets.MethodsA total of 154 patients who underwent PCNL at our hospital between October 2019 and January 2022 were retrospectively reviewed. The development of post-PCNL SIRS was the primary endpoint of the study. Univariable analysis and multivariable logistic regression analysis were performed to identify independent risk factors of post-PCNL SIRS. A nomogram was constructed using the independent risk factors, and receiver operating characteristic (ROC) curves were drawn.ResultsThere were 50 patients (32.5%) who developed SIRS after PCNL. In multivariate analysis, positive urine culture (odds ratio [OR], 3.556; p = 0.048), long operation time (OR, 1.011; p = 0.027), high IL-2R (OR, 1.002; p = 0.018), low percentage of CD3+ cells (OR 0.931; p = 0.006), and high white blood cell (WBC) count (OR, 1.282; p = 0.044) were independent risk factors for post‐PCNL SIRS. These five significant variables were used to generate a nomogram that exhibited favorable fitting. The discrimination area under the ROC curves was 0.795.ConclusionsPatients with long operation times, positive urine cultures, high interleukin 2 receptor, high white blood cell counts, and low percentages of CD3+ cells may be at a higher risk of developing SIRS after PCNL. In these patients, cautious and comprehensive preoperative evaluations and appropriate treatment strategies should be considered.

Abstract Impaired oxidative metabolism is one of multi-variate factors leading to exercise intolerance in heart failure patients. The purpose of the study was to demonstrate the use of dynamic 31P magnetic resonance spectroscopy (MRS) and 31P magnetic resonance imaging (MRI) techniques to measure PCr resynthesis rate post-exercise as a biomarker for oxidative metabolism in skeletal muscle in HF patients and controls. In this prospective imaging study, we recruited six HF patients and five healthy controls. The imaging protocol included 31P-MRS, spectrally selective 3D turbo spin echo for 31P-MRI, and Dixon multi-echo GRE for fat–water imaging on a 3 T clinical MRI scanner. All the subjects were scanned pre-exercise, during plantar flexion exercise, and post-exercise recovery, with two rounds of exercise for 31P -MRS and 31P-MRI, respectively. Unpaired t-tests were used to compare 31P-MRS and 31P-MRI results between the HF and control cohorts. The results show that PCr resynthesis rate was significantly slower in the HF cohort compared to the controls using 31P-MRS (P = 0.0003) and 31P-MRI (P = 0.0014). 31P-MRI showed significant differences between the cohorts in muscle groups (soleus (P = 0.0018), gastrocnemius lateral (P = 0.0007) and gastrocnemius medial (P = 0.0054)). The results from this study suggest that 31P-MRS/31P-MRI may be used to quantify lower leg muscle oxidative metabolism in HF patients, with 31P-MRI giving an additional advantage of allowing further localization of oxidative metabolism deficits. Upon further validation, these techniques may serve as a potentially useful clinical imaging biomarker for staging and monitoring therapies in HF-patients.

Abstract 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.

Background: Emerging asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were detected and multiple cases were found to be SARS-CoV-2 positive again, which raised an alarm for the patients hospitalized after the coronavirus disease 2019 (COVID-19) pandemic. Objective: We investigated the risk and prevention of hospital transmission of SARS-CoV-2 to hospitalized urological patients. Design, setting, and participants: This is a retrospective study of 319 hospitalized urological patients enrolled between April 20, 2020 and May 11, 2020 from two tertiary hospitals in Wuhan, China. Intervention: Chest computed tomography (CT) images, nucleic acid tests (NATs), and serum antibody were examined at the outpatient department and 1 wk after admission for all patients. Outcome measurements and statistical analysis: The chest CT images, NATs, serum antibody results, and clinical data were collected and analyzed. Results and limitations: None of the 319 patients was found to be SARS-CoV-2 NAT positive. Ten and four patients were detected to be immunoglobulin (Ig)G and IgM positive, respectively. The chest CT features of 116 patients showed abnormal lung findings. During the 1-wk isolation, one patient initially being IgG positive only was found to be IgM positive, and another initially IgM-positive patient had a rising IgG level. Through risk assessment, we identified seven patients with very high and high risk for hospital transmission, and delayed the surgery while maintaining close follow-up. Five intermediate-risk patients were operated on successfully under paravertebral block or epidural anesthesia to avoid opening the airway with endotracheal intubation. The remaining 104 low-risk and 203 normal patients underwent normal surgery. Conclusions: Of the 319 patients, seven were identified as very high and high risk, which reinforced the importance of epidemic surveillance of discharged COVID-19 patients and asymptomatic infections. Five intermediate-risk patients were operated on successfully under regional anesthesia. Patient summary: Our experience of risk assessment and management practice may provide a strategy to prevent severe acute respiratory syndrome coronavirus 2 transmission to hospitalized urological patients after the coronavirus disease 2019 (COVID-19) pandemic.

Bladder cancer (BCa) is a common heterogeneous urinary system tumor with high malignancy and limited advancement in treatment. Limited understanding of BCa has not contributed to any significant progress in diagnosis or treatment, exploring the mechanisms underlying BCa has become an urgent research focus. Exosomes, a type of extracellular vesicle (EV), have drawn substantial interest for their important roles in mediating intracellular communication. Exosomes shuttle numerous bioactive molecules, and noncoding RNAs (ncRNAs) are among the most numerous. ncRNAs including microRNA, long noncoding RNA, and circular RNA are sorted and packaged into exosomes selectively and transferred into recipient cells to regulate their function. Exosomal ncRNAs are associated with hallmarks of BCa, such as proliferation, apoptosis, epithelial-mesenchymal transition (EMT), cell cycle arrest, lymphangiogenesis, and chemotherapy resistance. Exosomal ncRNAs can also be detected in urine and serum, making them encouraging biomarkers for BCa diagnosis and prognosis. More importantly, exosomes exhibit excellent biocompatibility and potential for diversified applications. The delivery of bioactive substances and drugs into specific cells has become a promising approach for precision therapy for BCa patients. In addition, cancer vaccines have also received increasing attention. In this review, we summarize the current research on the regulatory roles of exosomal ncRNAs in BCa tumorigenesis and progression, as well as their potential clinical value in accelerating the diagnosis and therapy of BCa.

Background: Intrarenal calcium oxalate (CaOx) crystals induce inflammation and kidney tubular cell injury, which are processes that involve TLR4/NF-κB signalling. A recent genome-wide gene expression profile analysis of Randall's plaques in CaOx stone patients revealed that the expression of the long noncoding RNA H19 was significantly upregulated. However, to date, its role in kidney CaOx stones has not been reported. Method: A Gene Expression Omnibus (GEO) dataset was utilized to analyse gene expression profiles. Luciferase reporter, Western blotting, qRT-PCR, immunofluorescence staining and reactive oxygen species (ROS) assays were employed to study the molecular mechanism of HMGB1/TLR4/NF-κB regulation by H19 and miR-216b. In vitro and in vivo assays were performed to further confirm the proinflammatory and prooxidative stress effects. Finding: H19 expression was significantly increased and positively correlated with the expression levels of HMGB1, TLR4 and NF-κB in Randall's plaques and glyoxylate-induced CaOx nephrocalcinosis mouse models. H19 interacted with miR-216b and suppressed its expression. Additionally, miR-216b inhibited HMGB1 expression by directly binding its 3′-untranslated region. Moreover, H19 downregulation inhibited HMGB1, TLR4 and NF-κB expression and suppressed CaOx nephrocalcinosis-induced renal tubular epithelial cell injury, NADPH oxidase, and oxidative stress in vivo and in vitro. Interestingly, miR-216b inhibition partially reversed the inhibitory effect of H19 knockdown on HMGB1 expression. Interpretation: We determined that H19 might serve as a facilitator in the process of CaOx nephrocalcinosis-induced oxidative stress and renal tubular epithelial cell injury, and we revealed that the interaction between H19 and miR-216b could exert its effect via the HMGB1/TLR4/NF-κB pathway. Funding: This work was supported by the National Nature Science Foundation of China (Nos. 8196030190, 8190033175, 81370805, 81470935, 81900645, 81500534, and 81602236). Keywords: H19, calcium oxalate, tubular epithelial cell injury, HMGB1, ceRNA

Histone lysine methyltransferases (HMT) comprise a subclass of epigenetic regulators; dysregulation of these enzymes affects gene expression, which may lead to tumorigenesis. Here, we performed an integrated analysis of 50 HMTs in bladder cancer and found intrinsic links between copy number alterations, mutations, gene expression levels, and clinical outcomes. Through integrative analysis, we identified six HMT genes (PRDM9, ASH1L, SETD3, SETD5, WHSC1L1, and KMT2D) that may play a key role in the development and progression of bladder cancer. Of these six HMTs, histone lysine N‐methyltransferase 2D (KMT2D) exhibited the highest mutation rate in bladder cancer. Our comparison of the mRNA and miRNA expression profiles of mutated and wild‐type KMT2D suggested that two signaling pathways (FOX1–miR‐1224‐5p–DLK1 and HIF/GATA5–miR‐133a‐3p–DRD5) may mediate the tumor suppressive effect of the KMT2D mutation. In summary, our findings indicate that mutations in HMT genes, especially KMT2D mutation, may play a role in the development of bladder cancer.

ObjectivesWe aimed to determine preoperative risk factors associated with pathologic T3a (pT3a) upstaging of clinical T1 (cT1) renal cell carcinomas (RCCs) and develop a novel model capable of accurately identifying those patients at high risk of harboring occult pT3a characteristics.MethodsA retrospective analysis of 1324 cT1 RCC patients who underwent partial nephrectomy (PN) or radical nephrectomy (RN) was performed. The study cohort was divided into training and testing datasets in a 70:30 ratio for further analysis. Univariable and multivariable logistic regression analyses were performed to identify predictors associated with cT1 to pT3a upstaging and subsequently, those significant risk factors were used to construct models. We used the area under the curve (AUC) to determine the model with the highest discrimination power. Decision curve analyses (DCAs) were applied to evaluate clinical net benefit associated with using the predictive models.ResultsThe rates of upstaging were 6.1% (n = 81), 5.8% (n = 54) and 6.8% (n = 27) in the total population, training cohort and validation cohort, respectively. Tumor size, clinical T stage, R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior) nephrometry score, lymphocyte to monocyte ratio (LMR), prognostic nutrition index (PNI) and albumin to globulin ratio (AGR) were significantly associated with pT3a upstaging. The model that consisted of R.E.N.A.L. score, LMR, AGR and PNI achieved the highest AUC of 0.70 in the validation cohort and yielded the highest net benefit. In the subpopulation with complete serum lipid profile, the inclusion of low-density lipoprotein cholesterol (LDL-C) and Castelli risk index-I (CRI-I) significantly improved the discrimination of model (AUC = 0.86).ConclusionsOur finding highlights the importance of systemic inflammation response markers and serum lipid parameters in predicting pT3a upstaging. Our model had relatively good discrimination in predicting occult pT3a disease among patients with cT1 renal lesions, and the use of the model may be greatly beneficial to urologists in risk stratification and management decisions.

Due to the advantages of a high total pressure coefficient, large flow coefficient, and high efficiency, the diagonal flow fan is widely used in people’s livelihood and industrial fields. However, the design of the diagonal flow fan is mostly empirical, multi-solution, and comprehensive. The traditional optimization design process often consumes huge computing resources. In this paper, the diagonal flow fan blade is parameterized, the design variables are determined, and the accuracy of the parameterization method is verified. The maximum fitting error is controlled at approximately 0.1%. Based on the parametric design of blades, this paper organically integrates the traditional Kriging model and RBF model, and introduces the Ensemble of surrogates model (ES) to verify that the ES model has higher prediction accuracy in the prediction of fan flow and total pressure efficiency than the traditional prediction model. Subsequently, the Pareto optimal solution set of the approximate model within the global design scope is searched by NSGA-II. The numerical simulation and experimental verification show that the actual flow of the fan increases by 10% and the efficiency of the full pressure increases by 3.2% under the design condition of the optimized blade. The optimized model can significantly improve its air performance.

Prostate cancer (PCa) cells are heterogeneous, containing a variety of cancer cells with phenotypical and functional discrepancies in the tumor microenvironment, where prostate cancer stem cells (PCSCs) play a vital role in PCa development. Our earlier studies have shown that ALDHhiCD44+ (DP) PCa cells and the corresponding ALDHloCD44– (DN) PCa cells manifest as PCSCs and non-PCSCs, respectively, but the underlying mechanisms regulating stemness of the PCSCs are not completely understood. To tackle this issue, we have performed RNA-Sequencing and bioinformatic analysis in DP (versus DN) cells in this study. We discovered that, PER3 (period circadian regulator 3), a circadian rhythm gene, is significantly downregulated in DP cells. Overexpression of PER3 in DP cells significantly suppressed their sphere- and colony-forming abilities as well as tumorigenicity in immunodeficient hosts. In contrast, knockdown of PER3 in DN cells dramatically promoted their colony-forming and tumor-initiating capacities. Clinically, PER3 is downregulated in human prostate cancer specimens and PER3 expression levels are highly correlated with the prognosis of the PCa patient. Mechanistically, we observed that low levels of PER3 stimulates the expression of BMAL1, leading to the phosphorylation of β-catenin and the activation of the WNT/β-catenin pathway. Together, our results indicate that PER3 negatively regulates stemness of PCSCs via WNT/β-catenin signaling in the tumor microenvironment, providing a novel strategy to treat PCa patients.

In order to enhance the fluid mixing in the stirred tank and reduce the power consumption under the condition of full baffle, a sinusoidal sawtooth baffle was established in the present study. Based on the Eulerian–Eulerian method, a numerical simulation of the mixed flow in the stirred tank was conducted, and the reliability of the simulation method was verified by means of PIV experiments. The different structural characteristics of a standard baffle and the sine baffle were compared, to explore the effect of the modified baffle on flow mixing and power consumption in the tank. The outcomes indicate that the sinusoidal sawtooth structure had the effect of reducing drag and shunting, which could lessen the backflow on the backside of the baffle, strengthen the intensity of fluid turbulence and strain rate, improve the uniformity of particle distribution, and significantly lower the power consumption. When the relative tooth height was 0.333 and the relative tooth width was 0.028, the power consumption was reduced by 11.7%.

A landslide susceptibility model based on a metaheuristic optimization algorithm (germinal center optimization (GCO)) and support vector classification (SVC) is proposed and applied to landslide susceptibility mapping in the Three Gorges Reservoir area in this paper. The proposed GCO-SVC model was constructed via the following steps: First, data on 11 influencing factors and 292 landslide polygons were collected to establish the spatial database. Then, after the influencing factors were subjected to multicollinearity analysis, the data were randomly divided into training and testing sets at a ratio of 7:3. Next, the SVC model with 5-fold cross-validation was optimized by hyperparameter space search using GCO to obtain the optimal hyperparameters, and then the best model was constructed based on the optimal hyperparameters and training set. Finally, the best model acquired by GCO-SVC was applied for landslide susceptibility mapping (LSM), and its performance was compared with that of 6 popular models. The proposed GCO-SVC model achieved better performance (0.9425) than the genetic algorithm support vector classification (GA-SVC; 0.9371), grid search optimized support vector classification (GRID-SVC; 0.9198), random forest (RF; 0.9085), artificial neural network (ANN; 0.9075), K-nearest neighbor (KNN; 0.8976), and decision tree (DT; 0.8914) models in terms of the area under the receiver operating characteristic curve (AUC), and the trends of the other metrics were consistent with that of the AUC. Therefore, the proposed GCO-SVC model has some advantages in LSM and may be worth promoting for wide use.

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.

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.

Improvement of stirring performance is one of the primary objectives in solid–liquid mixing processes, such as the preparation of phase change materials (PCMs) for energy saving in refrigeration and heat pump systems. In this paper, three novel impellers are proposed: pitched-blade punched turbine (PBPT), bionic cut blade turbine (BCBT) and bionic cut punched blade turbine (BCPBT). An experimental test was conducted to validate the stirring system model based on the Eulerian–Eulerian method with the kinetic theory of granular flow. Then the performance of the novel impellers was predicted, studied, and compared. The outcomes indicate that a novel impeller, specifically BCPBT, can effectively suspend particles and dramatically reduce power consumption. A better solid–liquid suspension quality was obtained with an aperture diameter of 8 mm and aperture ratio of 13%. Within the range of impeller speeds and liquid viscosity studied in this this paper, higher impeller speeds and more viscous liquids are more conducive to particle dispersion. One of the most important contributions of this work lies in the design of novel impellers, an extent of energy conservation to 17% and efficient mixing was achieved. These results have reference significance for improving the energy efficiency of temperature regulation systems.

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.

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.

A 52-year-old Hispanic male presented with hematuria and was later diagnosed with a large invasive high-grade urothelial cell carcinoma (UCC) of the urinary bladder, but with ambiguous pT1/pT2 staging regarding musclaris propria invasion by UCC. The conventional treatment including radical cystoprostatectomy followed by neoadjuvant chemotherapy with or without radiation therapy was presented. The patient decided to delay the standard therapy until a later stage, but elected to go through transurethral resection of bladder tumor (TURBT) without Bacillus Calmette-Guérin instillation. Following TURBT, the patient started oral Boswellia sacra gum resin (aka frankincense or Ru Xiang in Chinese) hydrodistillates (BSGRH) administration at 3 mL daily with lifestyle changes, and continued this regimen in the last 25 months. Within the first year after diagnosis, the patient experienced 2 recurrences. Recurrent tumors were removed by TURBT alone and both tumors were far smaller than the original one. After the second recurrence, the patient has no detectible cancer in the bladder based on cystoscopy for 14 months and has an intact genitourinary system. His liver and kidney functions are considered to be normal based on blood chemistry tests. This index case suggests that BSGRH may have cancer chemopreventive effects on UCC. The use of Boswellia -derived products in the management of cancer has been well document in other published studies, and boswellic acids have been suggested to be the major component. However, BSGRH contains very little boswellic acids. Demonstration of cancer chemoprevention using BSGRH is one step forward in isolating the key components other than boswellic acids in frankincense. The critical question as to whether these components can simultaneously activate multiple pathways in cancer cells to execute cancer suppression/cytotoxicity or prevention effects remains to be addressed. More studies including identification of key molecules, pharmacokinetics of major compounds, as well as long-term benefits and possible adverse effects will be needed to meet the guidelines of the US Food and Drug Administration for botanical drug development.

The purpose of this study is to assess the repeatability of the quantification of pseudo-intracellular sodium concentration (C1) and pseudo-extracellular volume fraction (α) estimated in brain in vivo using sodium magnetic resonance (MRI) at 3 T. Eleven healthy subjects were scanned twice, with two sodium MRI acquisitions (with and without fluid suppression by inversion recovery), and two double inversion recovery (DIR) proton MRI. DIR MRIs were used to create masks of gray and white matter (GM, WM), that were subsequently applied to the C1 and α maps calculated from sodium MRI and a tissue three-compartment model, in order to measure the distributions of these two parameters in GM, WM or full brain (GM+WM) separately. The mean, median, mode, standard deviation (std), skewness and kurtosis of the C1 and α distributions in whole GM, WM and full brain were calculated for each subject, averaged over all data, and used as parameters for the repeatability assessment. The coefficient of variation (CV) was calculated as a measure of reliability for the detection of intra-subject changes in C1 and αfor each parameter, while intraclass correlation (ICC) was used as a measure of repeatability. It was found that the CV of most of the parameters was around 10-20% (except for C1 kurtosis which is about 40%) for C1 and α measurements, and that ICC was moderate to very good (0.4 to 0.9) for C1 parameters and for some of the α parameters (mainly skewness and kurtosis). In conclusion, the proposed method could allow to reliably detect changes of 50% and above of the different measurement parameters of C1 and αin neuropathologies (multiple sclerosis, tumor, stroke, Alzheimer's disease) compared to healthy subjects, and that skewness and kurtosis of the distributions of C1 and αseem to be the more sensitive parameters to these changes.

BACKGROUND AND OBJECTIVE: More recently laparoscopic radical cystectomy (LRC) has increasingly been an attractive alternative to open radical cystectomy (ORC) and many centers have reported their early experiences in the treatment of bladder cancer. Evaluate the safety and efficacy of LRC compared with ORC in the treatment of bladder cancer. METHODS: A systematic search of Medline, Scopus, and the Cochrane Library was performed up to Mar 1, 2013. Outcomes of interest assessing the two techniques included demographic and clinical baseline characteristics, perioperative, pathologic and oncological variables, and post-op neobladder function and complications. RESULTS: Sixteen eligible trials evaluating LRC vs ORC were identified including seven prospective and nine retrospective studies. Although LRC was associated with longer operative time (p

Calcium oxalate monohydrate (COM) is the major crystalline component in kidney stones and its adhesion to renal tubular cells leads to tubular injury. However, COM-induced toxic effects in renal tubular cells remain ambiguous. MicroRNAs (miRNAs) play an important role in gene regulation at the posttranscriptional levels.The present study aimed to assess the potential changes in microRNAs of proximal renal tubular cells in response to the adhesion of calcium oxalate monohydrate (COM) crystals.Lactate dehydrogenase (LDH) activity and DAPI staining were used to measure the toxic effects of HK-2 cells exposed to COM crystals. MicroRNA microarray and mRNA microarray were applied to evaluate the expression of HK-2 cells exposed to COM crystals. Quantitative real-time PCR (qRT-PCR) technology was used to validate the microarray results. Target prediction, Gene Ontology (GO) analysis and pathway analysis were applied to predict the potential roles of microRNAs in biological processes.Our study showed that COM crystals significantly altered the global expression profile of miRNAs in vitro. After 24 h treatment with a dose (1 mmol/L), 25 miRNAs were differentially expressed with a more than 1.5-fold change, of these miRNAs, 16 were up-regulated and 9 were down-regulated. A majority of these differentially expressed miRNAs were associated with cell death, mitochondrion and metabolic process. Target prediction and GO analysis suggested that these differentially expressed miRNAs potentially targeted many genes which were related to apoptosis, regulation of metabolic process, intracellular signaling cascade, insulin signaling pathway and type 2 diabetes.Our study provides new insights into the role of miRNAs in the pathogenesis associated with nephrolithiasis.

BACKGROUND: A common single nucleotide polymorphism (SNP), rs3802842, located at 11q23, was identified by genome-wide association studies (GWAS) to be significantly associated with the risk of colorectal cancer (CRC); however, the results of following replication studies were not always concordant. Thus, a case-control study and a meta-analysis were performed to clearly discern the effect of this variant in CRC. METHOD AND FINDINGS: We determined the genotypes of rs3802842 in 641 unrelated Chinese patients with CRC and 1037 cancer-free controls. Additionally, a meta-analysis comprising current and previously published studies was conducted. In our case-control study, significant associations between the polymorphism and CRC risk were observed in all genetic models, with an additive OR being 1.45 (95% CI = 1.26-1.67). The meta-analysis of 38534 cases and 39446 controls further confirmed the significant associations in all genetic models but with obvious between-study heterogeneity. Nevertheless, ethnicity, study type and whether subjects affected by Lynch syndrome could synthetically accounted for the heterogeneity. Besides, the cumulative and sensitivity analyses indicated the robust stability of the results. CONCLUSION: The results from our case-control study and meta-analysis provided convincing evidence that rs3802842 significantly contributed to CRC risk.

BACKGROUND: Long noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. They are aberrantly expressed in many types of cancers. In this study, we described lncRNAs profiles in 6 pairs of human renal clear cell carcinoma (RCCC) and the corresponding adjacent nontumorous tissues (NT) by microarray. METHODOLOGY/PRINCIPAL FINDINGS: With abundant and varied probes accounting 33,045 LncRNAs in our microarray, the number of lncRNAs that expressed at a certain level could be detected is 17157. From the data we found there were thousands of lncRNAs that differentially expressed (≥ 2 fold-change) in RCCC tissues compared with NT and 916 lncRNAs differentially expressed in five or more of six RCCC samples. Compared with NT, many lncRNAs were significantly up-regulated or down-regulated in RCCC. Our data showed that down-regulated lncRNAs were more common than up-regulated ones. ENST00000456816, X91348, BC029135, NR_024418 were evaluated by qPCR in sixty-three pairs of RCCC and NT samples. The four lncRNAs were aberrantly expressed in RCCC compared with matched histologically normal renal tissues. CONCLUSIONS/SIGNIFICANCE: Our study is the first one to determine genome-wide lncRNAs expression patterns in RCCC by microarray. The results displayed that clusters of lncRNAs were aberrantly expressed in RCCC compared with NT samples, which revealed that lncRNAs differentially expressed in tumor tissues and normal tissues may exert a partial or key role in tumor development. Taken together, this study may provide potential targets for future treatment of RCCC and novel insights into cancer biology.

BACKGROUND: Excess body weight measured as body mass index (BMI) has a positive association with risk of common cancers. However, previous meta-analyses related to BMI and liver cancer had inconsistent results. The purpose of the current study is to establish a nonlinear dose-response relationship between BMI and incidence risk of liver cancer. METHODS: A systematic literature search for relevant articles published from 1966 to November 2011 was conducted in PUBMED and EMBASE digital databases. Additional articles were manually searched by using the reference lists of identified papers. Restricted cubic splines and generalized least-squares regression methods were used to model a potential curvilinear relationship and to make a dose-response meta-analysis. Stratified analysis, sensitivity analysis and assessment of bias were performed in our meta-analysis. RESULTS: 8 articles including 1,779,471 cohort individuals were brought into meta-analysis. A non-linear dose-response association between BMI and risk of liver cancer was visually significant (P for nonlinearity0.1), and all value of BMI still presented significantly increased risk of cancer. CONCLUSIONS: The findings from meta-analysis provided that excess BMI had significant increased association with risk of liver cancer, although the biological mechanisms underlying the obesity-cancer link still need to be clarified.