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We investigate the spatial distribution and dynamics of the vortices in rotating Rayleigh–Bénard convection in a reduced Rayleigh number range $1.3\le Ra/Ra_{c}\le 83.1$. Under slow rotations ($Ra\approx 80\,Ra_{c}$), the vortices are distributed randomly, which is manifested by the size distribution of the Voronoi cells of the vortex centres being a standard $\varGamma$ distribution. The vortices exhibit Brownian-type horizontal motion in the parameter range $Ra\gtrsim 10\,Ra_{c}$. The probability density functions of the vortex displacements are, however, non-Gaussian at short time scales. At modest rotating rates ($4\,Ra_{c}\le Ra\lesssim 10\,Ra_{c}$), the centrifugal force leads to radial vortex motions, i.e. warm cyclones (cold anticyclones) moving towards (outwards from) the rotation axis. The horizontal scale of the vortices decreases with decreasing $Ra/Ra_c$ , and the size distribution of their Voronoi cells deviates from the $\varGamma$ distribution. In the rapidly rotating regime ($1.6\,Ra_{c}\le Ra\le 4\,Ra_{c}$), the vortices are densely distributed. The hydrodynamic interaction of neighbouring vortices results in the formation of vortex clusters. Within clusters, cyclones exhibit inverse-centrifugal motion as they submit to the outward motion of the strong anticyclones, and the radial velocity of the anticyclones is enhanced. The radial mobility of isolated vortices, scaled by their vorticity strength, is shown to be a simple power function of the Froude number. For all flow regimes studied, we show that the number of vortices with a lifespan greater than $t$ decreases exponentially as $\exp ({-t/{\tau }})$ for large time, where $\tau$ represents the characteristic lifetime of long-lived vortices. [ABSTRACT FROM AUTHOR]

The prognostic value and clinical relevance of tertiary lymphoid structures (TLSs) in intrahepatic cholangiocarcinoma (iCCA) remain unclear. Thus, we aimed to investigate the prognostic value and functional involvement of TLSs in iCCA. We retrospectively included 962 patients from 3 cancer centers across China. The TLSs at different anatomic subregions were quantified and correlated with overall survival (OS) by Cox regression and Kaplan-Meier analyses. Multiplex immunohistochemistry (mIHC) was applied to characterize the composition of TLSs in 39 iCCA samples. A quaternary TLS scoring system was established for the intra-tumor region (T score) and peri-tumor region (P score) respectively. T scores positively correlated with favorable prognosis (p < 0.001), whereas a high P score signified worse survival (p < 0.001). mIHC demonstrated that both T follicular helper and regulatory T cells were significantly increased in intra-tumoral TLSs compared to peri-tumoral counterparts (p < 0.05), and regulatory T cell frequencies within intra-tumoral TLSs were positively associated with P score (p < 0.05) rather than T score. Collectively, the combination of T and P scores stratified iCCAs into 4 immune classes with distinct prognoses (p < 0.001) that differed in the abundance and distribution pattern of TLSs. Patients displaying an immune-active pattern had the lowest risk, with 5-year OS rates of 68.8%, whereas only 3.4% of patients with an immune-excluded pattern survived at 5 years (p < 0.001). The C-index of the immune class was statistically higher than the TNM staging system (0.73 vs. 0.63, p < 0.001). These results were validated in an internal and 2 external cohorts. The spatial distribution and abundance of TLSs significantly correlated with prognosis and provided a useful immune classification for iCCA. T follicular helper and regulatory T cells may play a critical role in determining the functional orientation of spatially different TLSs. Tertiary lymphoid structures (TLSs) are associated with favorable prognosis in a number of cancers. However, their role in intrahepatic cholangiocarcinoma (iCCA) remains unclear. Herein, we comprehensively evaluated the spatial distribution, abundance, and cellular composition of TLSs in iCCA, and revealed the opposite prognostic impacts of TLSs located within or outside the tumor. This difference could be mediated by the different immune cell subsets present within the spatially distinct TLSs. Based on our analysis, we were able to stratify iCCAs into 4 immune subclasses associated with varying prognoses. [Display omitted] • Tertiary lymphoid structures (TLSs) within and outside the tumor have opposite prognostic impacts on patients with iCCA. • The heterogeneous distribution of Tfh and Treg cells within distinct TLSs might be a determinant of their functional state. • The geographic integration of TLSs stratified iCCAs into 4 immune subclasses with distinct clinical outcomes. [ABSTRACT FROM AUTHOR]

We take Graph $g={9.8}\ \textrm {m}\ \textrm {s}^{-2}$, Graph $\alpha ={1\times 10^{-4}}\ \textrm {K}^{{-1}}$ (Sohail I et al. i 2018), Graph $L=1\times 10^{7}\ \textrm {m}$, Graph $\varDelta ={10}\ \textrm {K}$, Graph $\kappa ={1\times 10^{-7}}\ \textrm {m}^2\ \textrm {s}^{-1}$ and Graph $\nu =1\times 10^{-6}\ \textrm {m}^2\ \textrm {s}^{-1}$ (Siggers, Kerswell & Balmforth 2004). The normalized height of topography Graph $h/H$ corresponds to Graph $0$, Graph $0.25$, Graph $0.5$ and Graph $0.75$ in figure 3( I a i - I d i ). Furthermore, as shown in figures 5 and 8, both Graph $\phi \tau$ and Graph $Nu$ increase as Graph $\omega$ decreases, and note that Graph $Nu$ is proportional to Graph $G(APE)$. In the current study, Graph $Ra$, Graph $Pr$ and Graph $\varGamma$ are fixed as Graph $Ra=1\times 10^{10}$, Graph $Pr=8.0$ and Graph $\varGamma =0.2$. Because Graph $\phi i$ is small compared with Graph $G(APE)$ for sufficiently large Graph $Ra$ (Peltier & Caulfield 2003; Gayen I et al. i 2013), Graph $\eta '$ asymptotically approaches its upper limit of 1 as Graph $Ra$ increases. [Extracted from the article]

Circular RNAs (circRNAs) are a class of regulatory RNAs with complex roles in healthy and diseased tissues. However, the oncogenic role of circRNAs in hepatocellular carcinoma (HCC) remains poorly understood, including the mechanisms by which the circular ubiquitin-binding associated protein 2 (circUBAP2) contributes to tumorigenesis. We analyzed the expression of circUBAP2 in 20 paired samples of HCC and healthy tissue as well as in seven HCC cell lines via quantitative real-time polymerase chain reaction. Functional experiments, such as CCK8 viability assays, colony formation assays, wound healing, transwell assays and flow cytometry, were conducted to assess the effects of circUBAP2 in vitro. To further elucidate the mechanisms by which circUBAP2 acts, we conducted dual-luciferase assays, western blots, RNA pull-down assays and rescue experiments. CircUBAP2 was highly upregulated in most HCC tissues and was associated with poor prognosis. HCC patients with high circUBAP2 expression had greater vascular invasion and worse differentiation. Functionally, circUBAP2 overexpression enhanced HCC cell proliferation, migration and invasion and inhibited apoptosis. Furthermore, we found that circUBAP2 upregulated c-Myc expression by sponging miR-1294, thus contributing to hepatocarcinogenesis. Inhibiting circUBAP2 expression in HCC attenuated the oncogenic effects of c-Myc. These findings suggest that circUBAP2 promotes HCC growth and metastasis. CircUBAP2 may have value as an independent prognostic biomarker or as a new target for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Background: It remains unclear whether the short-term benefits of laparoscopic repeat hepatectomy (LRH) accrue to patients with recurrent liver tumors. The present study aimed to report our own center's experience and perform a meta-analysis to evaluate the safety and feasibility of LRH in comparison with open repeat hepatectomy (ORH) for treating recurrent liver tumors. Patients and Methods: A propensity score–matched study was performed including 426 patients receiving LRH or ORH for recurrent hepatocellular carcinoma between January 2017 and December 2018. Surgical outcomes and perioperative inflammation-based markers, including monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune–inflammation index were collected from medical records and analyzed. Additionally, a systematic literature review was performed to identify relevant studies in PubMed, EMBASE, Web of Science, and Cochrane library databases up to October 1, 2020. Information including patient demographics, pathologic characteristics, and short-term outcomes was extracted and analyzed using random- or fixed-effects models. Results: Of 68 LRHs, 57 were matched with an ORH finally. Our study demonstrated that LRH was significantly associated with less intraoperative blood loss (50 vs. 100 mL; P < 0.001), lower rate of hepatic inflow occlusion (10.52 vs. 33.3%; P = 0.003), and shorter postoperative hospital stay (5 vs. 6 days; P = 0.001) after 1:1 propensity score matching. The operation time, rate of blood transfusion, and postoperative complications were similar between the two groups. Moreover, all four inflammation-based markers were significantly lower in LRH group on postoperative day 1. In the meta-analysis, a total of 12 studies comprising 1,315 patients receiving repeat hepatectomy met the selection criteria. Similar to our own study, the meta-analysis showed shorter hospital stay [standard mean difference (SMD) = −0.51, 95% confidence interval (CI) = −0.79 to −0.22, P < 0.001], less intraoperative blood loss (SMD = −0.79, 95% CI = −1.11 to −0.47, P < 0.001), and lower rate of major postoperative complications [odds ratio (OR) = 0.35, 95% CI = 0.19–0.66, P = 0.001] in the LRH group. There was no difference in the field of overall postoperative complication and operation time between LRH and ORH groups. Conclusion: Compared with ORH, LRH results in relatively better surgical outcomes and faster postoperative recovery. It could be considered a feasible and effective option for the treatment of recurrent liver tumors. [ABSTRACT FROM AUTHOR]

Liver cancer is a lethal disease that is associated with poor prognosis. In order to identify the functionally important genes associated with liver cancer that may reveal novel therapeutic avenues, we performed integrated analysis to profile miRNA and mRNA expression levels for liver tumors compared to normal samples in The Cancer Genome Atlas (TCGA) database. We identified 405 differentially expressed genes and 233 differentially expressed miRNAs in tumor samples compared with controls. In addition, we also performed the pathway analysis and found that mitogen-activated protein kinases (MAPKs) and G-protein coupled receptor (GPCR) pathway were two of the top significant pathway nodes dysregulated in liver cancer. Furthermore, by examining these signaling networks, we discovered that FOS (Fos proto-oncogene, AP-1 transcription factor subunit), LAMC2 (laminin subunit gamma 2), and CALML3 (calmodulin like 3) were the most significant gene nodes with high degrees involved in liver cancer. The expression and disease prediction accuracy of FOS, LAMC2, CALML3, and their interacting miRNAs were further performed using a HCC cohort. Finally, we investigated the prognostic significance of FOS in another HCC cohort. Patients with higher FOS expression displayed significantly shorter time to recurrence (TTR) and overall survival (OS) compared with patients with lower expression. Collectively, our study demonstrates that FOS is a potential prognostic marker for liver cancer that may reveal a novel therapeutic avenue in this lethal disease. [ABSTRACT FROM AUTHOR]

We report an experimental study of the distributions of temperature and solid fraction of growing $\text{NH}_{4}\text{Cl}$ – $\text{H}_{2}\text{O}$ mushy layers that are subjected to periodical cooling from below, focusing on late-time dynamics where the mushy layer oscillates about an approximate steady state. Temporal evolution of the local temperature $T(z,t)$ at various heights in the mush demonstrates that the temperature oscillations of the bottom cooling boundary propagate through the mushy layer with phase delays and substantial decay in the amplitude. As the initial concentration $C_{0}$ increases, we show that the decay rate of the thermal oscillation with height also decreases, and the propagation speed of the oscillation phase increases. We interpret this as a result of the solid fraction increasing with $C_{0}$ , which enhances the thermal conductivity but reduces the specific heat of the mushy layer. We present a new methodology to determine the distribution of solid fraction $\unicode[STIX]{x1D719}(z)$ in mushy layers for various $C_{0}$ , using only measurements of the temperature $T(z,t)$. The method is based on the phase behaviour during thermal modulation, and opens up a new approach for inferring mushy-layer properties in geophysical and engineering settings, where direct measurements are challenging. In our experiments, profiles of the solid fraction $\unicode[STIX]{x1D719}(z)$ exhibit a cliff–ramp–cliff structure with large vertical gradients of $\unicode[STIX]{x1D719}$ near the mush–liquid interface and also near the bottom boundary, but much more gradual variation in the interior of the mushy layer. Such a profile structure is more pronounced for higher initial concentration $C_{0}$. For very low concentration, the solid fraction appears to be linearly dependent on the height within the mush. The volume-average of the solid fraction, and the local fluctuations in $\unicode[STIX]{x1D719}(z)$ both increase as $C_{0}$ increases. We suggest that the fast increase of $\unicode[STIX]{x1D719}(z)$ near the bottom boundary is possibly due to diffusive transport of solute away from the bottom boundary and the depletion of solute content near the basal region. [ABSTRACT FROM AUTHOR]

We present studies of the solidification of binary aqueous solutions that undergo time-periodic cooling from below. We develop an experiment for solidification of aqueous $\text{NH}_{4}\text{Cl}$ solutions, where the temperature of the cooling boundary is modulated as a simple periodic function of time with independent variations of the modulation amplitude and frequency. The thickness of the mushy layer exhibits oscillations about the background growth obtained for constant cooling. We consider the deviation given by the difference between states with modulated and fixed cooling, which increases when the modulation amplitude increases but decreases with increasing modulation frequency. At early times, the deviation amplitude is consistent with a scaling argument for growth with quasi-steady modulation. In situ measurements of the mush temperature reveal thermal waves propagating through the mushy layer, with amplitude decaying with height within the mushy layer, whilst the phase lag behind the cooling boundary increases with height. This also leads to phase lags in the variation of the mushy-layer thickness compared to the boundary cooling. There is an asymmetry of the deviation of mushy-layer thickness: during a positive modulation (where the boundary temperature increases at the start of a cycle) the peak thickness deviation has a greater magnitude than the troughs in a negative modulation mode (where the boundary temperature decreases at the start of the cycle). A numerical model is formulated to describe mushy-layer growth with constant bulk concentration and turbulent heat transport at the mush–liquid interface driven by compositional convection associated with a finite interfacial solid fraction. The model recovers key features of the experimental results at early times, including the propagation of thermal waves and oscillations in mushy-layer thickness, although tends to overpredict the mean thickness. [ABSTRACT FROM AUTHOR]

We present a numerical study of quasistatic magnetoconvection in a cubic Rayleigh–Bénard (RB) convection cell subjected to a vertical external magnetic field. For moderate values of the Hartmann number $Ha$ (characterising the strength of the stabilising Lorentz force), we find an enhancement of heat transport (as characterised by the Nusselt number $Nu$). Furthermore, a maximum heat transport enhancement is observed at certain optimal $Ha_{opt}$. The enhanced heat transport may be understood as a result of the increased coherence of the thermal plumes, which are elementary heat carriers of the system. To our knowledge this is the first time that a heat transfer enhancement by the stabilising Lorentz force in quasistatic magnetoconvection has been observed. We further found that the optimal enhancement may be understood in terms of the crossing of the thermal and the momentum boundary layers (BL) and the fact that temperature fluctuations are maximum near the position where the BLs cross. These findings demonstrate that the heat transport enhancement phenomenon in the quasistatic magnetoconvection system belongs to the same universality class of stabilising–destabilising (S–D) turbulent flows as the systems of confined Rayleigh–Bénard (CRB), rotating Rayleigh–Bénard (RRB) and double-diffusive convection (DDC). This is further supported by the findings that the heat transport, boundary layer ratio and temperature fluctuations in magnetoconvection at the boundary layer crossing point are similar to the other three cases. A second type of boundary layer crossing is also observed in this work. In the limit of $Re\gg Ha$ , the (traditionally defined) viscous boundary $\unicode[STIX]{x1D6FF}_{v}$ is found to follow a Prandtl–Blasius-type scaling with the Reynolds number $Re$ and is independent of $Ha$. In the other limit of $Re\ll Ha$ , $\unicode[STIX]{x1D6FF}_{v}$ exhibits an approximate ${\sim}Ha^{-1}$ dependence, which has been predicted for a Hartmann boundary layer. Assuming the inertial term in the momentum equation is balanced by both the viscous and Lorentz terms, we derived an expression $\unicode[STIX]{x1D6FF}_{v}=H/\sqrt{c_{1}Re^{0.72}+c_{2}Ha^{2}}$ (where $H$ is the height of the cell) for all values of $Re$ and $Ha$ , which fits the obtained viscous boundary layer well. [ABSTRACT FROM AUTHOR]

Background: Microvascular invasion (MVI) is recognized as a prognostic factor associated with poor outcome in hepatocellular carcinoma (HCC) patients after curative resection. It remains unclear, however, whether MVI can provide prognostic information for patients at a specific tumor stage.Methods: Consecutive HCC patients who underwent curative resection in years of 2007 and 2008 (discovery cohort) were enrolled in this retrospective study. Patients were stratified by the Barcelona Clinic Liver Cancer (BCLC) staging system. The prognostic significance of MVI for overall survival (OS) and recurrence-free survival (RFS) was studied in each subgroup. The clinical significance of MVI was validated in another cohort of patients underwent curative surgery in the year of 2006 (validation cohort).Results: Of the 1540 patients in the discovery cohort, 389 (25.3%) patients had detectable MVI. Occurrence rates of MVI in the BCLC stage 0, A, and B subgroups were 12.4, 26.2, and 34.4%, respectively. In univariate analysis, MVI was associated with poor OS and RFS (P < 0.001 for both) in HCC patients at stage A, with poor OS in patients at stage 0 (P = 0.028), and with poor RFS at stage B (P = 0.039). In multivariate analysis, MVI was an independent risk factor for OS (HR = 1.431, 95% CI, 1.163-1.761, P < 0.001) and RFS (HR = 1.400, 95% CI, 1.150-1.705, P = 0.001) in patients at stage A; and an independent risk factor for RFS (P = 0.043) in patients at stage B. A similar clinical significance of MVI was found in the validation cohort.Conclusions: MVI has limited prognostic value for HCC patients at BCLC stages 0 and B. For those at stage A, MVI was associated with patient survival and may help to select patients with high risk of disease recurrence. [ABSTRACT FROM AUTHOR]

Objective: Tumour pathology contains rich information, including tissue structure and cell morphology, that reflects disease progression and patient survival. However, phenotypic information is subtle and complex, making the discovery of prognostic indicators from pathological images challenging., Design: An interpretable, weakly supervised deep learning framework incorporating prior knowledge was proposed to analyse hepatocellular carcinoma (HCC) and explore new prognostic phenotypes on pathological whole-slide images (WSIs) from the Zhongshan cohort of 1125 HCC patients (2451 WSIs) and TCGA cohort of 320 HCC patients (320 WSIs). A 'tumour risk score (TRS)' was established to evaluate patient outcomes, and then risk activation mapping (RAM) was applied to visualise the pathological phenotypes of TRS. The multi-omics data of The Cancer Genome Atlas(TCGA) HCC were used to assess the potential pathogenesis underlying TRS., Results: Survival analysis revealed that TRS was an independent prognosticator in both the Zhongshan cohort (p<0.0001) and TCGA cohort (p=0.0003). The predictive ability of TRS was superior to and independent of clinical staging systems, and TRS could evenly stratify patients into up to five groups with significantly different prognoses. Notably, sinusoidal capillarisation, prominent nucleoli and karyotheca, the nucleus/cytoplasm ratio and infiltrating inflammatory cells were identified as the main underlying features of TRS. The multi-omics data of TCGA HCC hint at the relevance of TRS to tumour immune infiltration and genetic alterations such as the FAT3 and RYR2 mutations., Conclusion: Our deep learning framework is an effective and labour-saving method for decoding pathological images, providing a valuable means for HCC risk stratification and precise patient treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Brownian motion of particles in fluid is the most common form of collective behavior in physical and biological systems. Here, we demonstrate through both experiment and numerical simulation that the movement of vortices in a rotating turbulent convective flow resembles that of inertial Brownian particles, i.e., they initially move ballistically and then diffusively after certain critical time. Moreover, the transition from ballistic to diffusive behaviors is direct, as predicted by Langevin, without first going through the hydrodynamic memory regime. The transitional timescale and the diffusivity of the vortices can be collapsed excellently onto a master curve for all explored parameters. In the spatial domain, however, the vortices exhibit organized structures, as if they are performing tethered random motion. Our results imply that the convective vortices have inertia-induced memory such that their short-term movement can be predicted and their motion can be well described in the framework of Brownian motions., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background: Microvascular invasion (MVI) is considered as one of the most powerful prognostic factors in hepatocellular carcinoma (HCC). Currently, it could only be diagnosed by post-operative histological examination. This study aimed to assess the diagnostic value of serum paraoxonase 1 (PON1) for MVI., Methods: In this study, we analyzed data from 754 HCC patients who underwent surgical treatment between December 2010 and November 2011. Serum PON1 was measured by ELISA and receiver operating characteristic (ROC) curve was applied to calculate diagnostic accuracy., Results: MVI was detected in 174 of 505 patients (34.5%) in the test cohort and 84 of 249 patients (33.7%) in the validation cohort. Univariate analyses indicated tumor size, AFP, and PON1 were significantly related with vascular invasion status. ROC curves determined the optimum diagnostic cutoff value for PON1 was 191.12 ng/mL (AUC 0.754, 95% CI: 0.710-0.798, sensitivity 70.67%, specificity 78.11% in the test cohort), which was significantly better than AFP (cutoff value 279.8 ng/mL, AUC 0.666, 95% CI: 0.618-0.714, sensitivity 40.38%, specificity 85.19%, P=0.0063). In the sHCC sub-group, PON1 retained diagnostic value (AUC 0.738, 95% CI: 0.680-0.796, sensitivity 72.82%, specificity 76.57% in the test cohort), while AFP failed to do so (AUC 0.579, 95% CI: 0.511-0.647, sensitivity 26.21%, specificity 86.84%, P=0.0003). These results were further confirmed by the validation cohort. The combination of PON1 and AFP increased the diagnostic accuracy for vascular invasion compared with either test alone (AUC 0.785, 95% CI: 0.744-0.826, sensitivity 75.96%, specificity 77.44%; PON1 plus AFP vs . PON1 alone, P=0.0004; PON1 plus AFP vs. AFP alone, P<0.0001)., Conclusions: Serum PON1 could potentially be used to diagnose MVI and could be used to guide more personalized treatment strategy., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Objectives: Organ donation after brain death followed by circulatory death is practiced in China. This study evaluated the application of normothermic regional perfusion to protect the liver grafts from these donors from warm ischemia in a large transplant center in China., Materials and Methods: This prospective study involved 19 liver transplants from brain death followed by circulatory death donors that were conducted between December 2014 and June 2017. We evaluated the baseline characteristics of the donors and recipients and compared outcomes of both groups. Graft and recipient survival and postoperative complications were also analyzed., Results: Although the normothermic regional perfusion group consisted of marginal donors with prolonged warm ischemia and recipients with higher Model for End-Stage Liver Disease scores (P < .05), postoperative tests indicated no differences in liverfunction recovery in both groups. Furthermore, total bilirubin decreased significantly faster in the normothermic regional perfusion group than in the control group (P < .05). Both groups showed similar 1-year recipient survival rates. No recipients in the normothermic regional perfusion group had any biliary complications, whereas 2 recipients in the control group developed ischemic cholangiopathy and received invasive treatment during follow-up., Conclusions: In situ normothermic regional perfusion demonstrated a significant benefit in grafts from brain death followed by circulatory death donors and could potentially increase both the number and quality of donated organs.

Recent studies have found that selenium-binding protein 1 (SBP1) is downregulated in various malignant tumors. Nevertheless, the role of SBP1 in intrahepatic cholangiocarcinoma (ICC) is largely unknown. In the present study, we aimed to explore the clinical significance and biological function of SBP1 in ICC. Western blotting and immunohistochemistry were performed to evaluate SBP1 expression in ICC tissues, and correlations between SBP1 and clinicopathological parameters were further assessed. The prognostic significance of SBP1 in ICC patients was evaluated via Kaplan-Meier and Cox regression analyses. Moreover, we used RBE, a human ICC cell line, to study the effects of SBP1 knockdown on ICC cell proliferation, migration and invasion. Finally, the expression levels of epithelial-mesenchymal transition-related markers, including snail, vimentin, and E-cadherin, were investigated via Western blotting and immunohistochemistry. The results showed that SBP1 expression was significantly downregulated in ICC tumor tissues, especially in tumor tissues from ICC patients with recurrence or tumor vascular invasion, compared with that in peritumoral tissues (all P < 0.05). In addition, the reduction in SBP1 expression was related to microvascular invasion, lymphatic metastasis, and tumor-node-metastasis (TNM) stage (all P < 0.05). Furthermore, the SBP1 expression level was an independent prognostic factor in ICC ( P < 0.05). Knockdown of SBP1 resulted in decreased in vitro proliferation, migration and invasion ability. Low SBP1 expression also resulted in the upregulation of mesenchymal markers such as vimentin and snail. In conclusion, SBP1 may be a prognostic indicator for patients with ICC as well as a potential target for ICC treatment., Competing Interests: None.

Decreased selenium-binding protein 1 (SBP1) is associated with increased invasion and poor prognosis of hepatocellular carcinoma (HCC). However, the underlying mechanism remains unknown. To unravel this mechanism, HCC cells expressing SBP1 were constructed and the impact on migration, invasion, and epithelial-mesenchymal transition (EMT) was evaluated. SBP1 expression reduced HCC cell migration and invasion by inhibiting EMT. Gene expression profiles of control and SBP1 expressing HCC cells revealed 186 differentially expressed genes, of which fibroblast growth factor 5, vascular endothelial growth factor receptor 1, and C-X-C motif chemokine receptor 4 ( CXCR4 ) showed the greatest differences. CXCR4 expression was inhibited by SBP1 and restored the migration and invasion ability of HCC cells through activation of AKT signaling. Tumor samples from 200 HCC patients supported our in vitro findings and revealed an inverse correlation between SBP1 and CXCR4 expression. Patients with low SBP1 and high CXCR4 expression had the poorest prognosis and survival rate. Our results suggest that downregulation of SBP1 induces increased CXCR4 expression and results in EMT of HCC cells. Together, SBP1 and CXCR4 are promising potential biomarkers and therapeutic targets for HCC patients., Competing Interests: None.

We report an experimental observation of a flow topology transition via global bifurcation in a turbulent Rayleigh-Bénard convection. This transition corresponds to a spontaneous symmetry breaking with the flow becomes more turbulent. Simultaneous measurements of the large-scale flow (LSF) structure and the heat transport show that the LSF bifurcates from a high heat transport efficiency quadrupole state to a less symmetric dipole state with a lower heat transport efficiency. In the transition zone, the system switches spontaneously and stochastically between the two long-lived metastable states.

Background: Microvascular invasion (MVI) is recognized as a prognostic factor associated with poor outcome in hepatocellular carcinoma (HCC) patients after curative resection. It remains unclear, however, whether MVI can provide prognostic information for patients at a specific tumor stage., Methods: Consecutive HCC patients who underwent curative resection in years of 2007 and 2008 (discovery cohort) were enrolled in this retrospective study. Patients were stratified by the Barcelona Clinic Liver Cancer (BCLC) staging system. The prognostic significance of MVI for overall survival (OS) and recurrence-free survival (RFS) was studied in each subgroup. The clinical significance of MVI was validated in another cohort of patients underwent curative surgery in the year of 2006 (validation cohort)., Results: Of the 1540 patients in the discovery cohort, 389 (25.3%) patients had detectable MVI. Occurrence rates of MVI in the BCLC stage 0, A, and B subgroups were 12.4, 26.2, and 34.4%, respectively. In univariate analysis, MVI was associated with poor OS and RFS (P < 0.001 for both) in HCC patients at stage A, with poor OS in patients at stage 0 (P = 0.028), and with poor RFS at stage B (P = 0.039). In multivariate analysis, MVI was an independent risk factor for OS (HR = 1.431, 95% CI, 1.163-1.761, P < 0.001) and RFS (HR = 1.400, 95% CI, 1.150-1.705, P = 0.001) in patients at stage A; and an independent risk factor for RFS (P = 0.043) in patients at stage B. A similar clinical significance of MVI was found in the validation cohort., Conclusions: MVI has limited prognostic value for HCC patients at BCLC stages 0 and B. For those at stage A, MVI was associated with patient survival and may help to select patients with high risk of disease recurrence.