CYP2E1 deficit mediates cholic acid-induced malignant growth in hepatocellular carcinoma cells.

BACKGROUND: Increased level of serum cholic acid (CA) is often accompanied with decreased CYP2E1 expression in hepatocellular carcinoma (HCC) patients. However, the roles of CA and CYP2E1 in hepatocarcinogenesis have not been elucidated. This study aimed to investigate the roles and the underlying mechanisms of CYP2E1 and CA in HCC cell growth. METHODS: The proteomic analysis of liver tumors from DEN-induced male SD rats with CA administration was used to reveal the changes of protein expression in the CA treated group. The growth of CA-treated HCC cells was examined by colony formation assays. Autophagic flux was assessed with immunofluorescence and confocal microscopy. Western blot analysis was used to examine the expression of CYP2E1, mTOR, AKT, p62, and LC3II/I. A xenograft tumor model in nude mice was used to examine the role of CYP2E1 in CA-induced hepatocellular carcinogenesis. The samples from HCC patients were used to evaluate the clinical value of CYP2E1 expression. RESULTS: CA treatment significantly increased the growth of HCC cells and promoted xenograft tumors accompanied by a decrease of CYP2E1 expression. Further studies revealed that both in vitro and in vivo, upregulated CYP2E1 expression inhibited the growth of HCC cells, blocked autophagic flux, decreased AKT phosphorylation, and increased mTOR phosphorylation. CYP2E1 was involved in CA-activated autophagy through the AKT/mTOR signaling. Finally, decreased CYP2E1 expression was observed in the tumor tissues of HCC patients and its expression level in tumors was negatively correlated with the serum level of total bile acids (TBA) and gamma-glutamyltransferase (GGT). CONCLUSIONS: CYP2E1 downregulation contributes to CA-induced HCC development presumably through autophagy regulation. Thus, CYP2E1 may serve as a potential target for HCC drug development.

Study on the detonation wave propagation of shaped charge with three-layer liner and its driving characteristics to liner.

With the continuous improvement of various armor protection technologies, the armor protection performance has increased significantly, and then the damage performance requirements of armor-piercing ammunition have also increased. In order to improve the penetration ability of the liner, a new three-layer liner structure is designed in this paper. The jet forming process was simulated by AUTODYN software. The mechanism of shaped jet forming of three-layer liner was studied. The reason why the penetration depth of three-layer liner was higher than that of ordinary liner was explained. The influence of three-layer liner on the propagation of detonation wave and the change of pressure when detonation wave acted on liner were found, which provided a new idea for improving the penetration depth of jet. The influence of liner material, cone angle and stand-off on jet forming and penetration was also studied by orthogonal optimization experiment, and the structural parameters with the best penetration performance were obtained. The results show that the pressure at the convergence point increases first and then decreases during the formation of the jet of the three-layer liner. The pressure at the convergence point when the three-layer liner material is from low impedance to high impedance from the outside to the inside is much larger than the pressure at the convergence point from high impedance to low impedance. When the three-layer liner material is Al 2024-Copper-Tantalum from the outside to the inside, the pressure at the convergence point of the three-layer liner at different times is higher than that of the double-layer liner and the single-layer liner. Reasonable matching of different impact impedance materials in the three-layer liner can greatly improve the pressure value of the detonation wave acting on the cone liner. The maximum pressure at the convergence point on the axis is 39.10 GPa, which is 22.00% higher than that of the double-layer liner at the convergence point, and 53.03% higher than that of the single-layer liner at the convergence point. The orthogonal design test scheme is simulated and analyzed. The penetration depth is taken as the observation index, and the range analysis is adopted. The results show that the material matching of the three-layer liner has the greatest influence on the depth of the jet penetrating the target plate, followed by the cone angle of the three-layer liner. Relatively speaking, the stand-off has the least influence on the result. Reasonable matching of materials with different impact impedances in the three-layer liner can maximize the penetration depth of the jet into the target plate.

Development and validation of a machine learning-based early prediction model for massive intraoperative bleeding in patients with primary hepatic malignancies.

BACKGROUND: Surgical resection remains the primary treatment for hepatic malignancies, and intraoperative bleeding is associated with a significantly increased risk of death. Therefore, accurate prediction of intraoperative bleeding risk in patients with hepatic malignancies is essential to preventing bleeding in advance and providing safer and more effective treatment. AIM: To develop a predictive model for intraoperative bleeding in primary hepatic malignancy patients for improving surgical planning and outcomes. METHODS: The retrospective analysis enrolled patients diagnosed with primary hepatic malignancies who underwent surgery at the Hepatobiliary Surgery Department of the Fourth Hospital of Hebei Medical University between 2010 and 2020. Logistic regression analysis was performed to identify potential risk factors for intraoperative bleeding. A prediction model was developed using Python programming language, and its accuracy was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Among 406 primary liver cancer patients, 16.0% (65/406) suffered massive intraoperative bleeding. Logistic regression analysis identified four variables as associated with intraoperative bleeding in these patients: ascites [odds ratio (OR): 22.839; P < 0.05], history of alcohol consumption (OR: 2.950; P < 0.015), TNM staging (OR: 2.441; P < 0.001), and albumin-bilirubin score (OR: 2.361; P < 0.001). These variables were used to construct the prediction model. The 406 patients were randomly assigned to a training set (70%) and a prediction set (30%). The area under the ROC curve values for the model's ability to predict intraoperative bleeding were 0.844 in the training set and 0.80 in the prediction set. CONCLUSION: The developed and validated model predicts significant intraoperative blood loss in primary hepatic malignancies using four preoperative clinical factors by considering four preoperative clinical factors: ascites, history of alcohol consumption, TNM staging, and albumin-bilirubin score. Consequently, this model holds promise for enhancing individualised surgical planning.

Main Control Factors of Fracture Propagation in Reservoir: A Review.

The fracture distribution and internal control factors after the fracturing of unconventional oil and gas reservoirs determine the reservoir reforming effect to a large extent. Based on the research of global scholars on the influencing factors of fracture propagation, comprehensive theoretical model, and numerical simulation, this Review systematically discusses the influence of internal geological factors and external engineering factors of unconventional oil and gas reservoir on fracture propagation behavior and summarizes the current problems and development trends in fracture research. The results show the following: (1) The fracture propagation is a comprehensive process constrained by lithology and mineral composition, water saturation, nonhomogeneity, natural weak surface, and ground stress. (2) External engineering factors have a meaningful control effect on fracture propagation; the type and temperature of fracturing fluids can also change the mechanical properties of different rocks, thus affecting the fracture propagation pattern. (3) The existing fracture propagation models have certain limitations, and their computational reliability still needs to be further verified. (4) Numerical simulation can break through the limitations of physical simulation, but different simulation methods have different shortcomings and applicability. In the future, we should focus on: (1) finding parameters to quantitatively characterize heterogeneity at the 3D level, which is an important direction to study the effect of heterogeneity on fracture propagation; (2) introducing computerized methods to establish a geological model that considers multiple factors and combining it with numerical simulation software to study fracture propagation; (3) considering the characteristics of fluid-liquid-solid phase comprehensively, establishing a suitable THL coupling equation; (4) how the interaction mode of fracturing fracture is combined with the natural fracture geometry, and how the fracture is affected by fracturing engineering parameters such as fluid injection rate and viscosity of fracturing fluid; and (5) geology-engineering dynamic integration, which is an important direction to be carried out in the future.

Event-triggered adaptive control for nonlinear systems using time-receding horizons without initial dependence.

This paper investigates the full-state constraint event-triggered adaptive control for a class of uncertain strict-feedback systems. The lack of information on the coupling dynamics of virtual variables in backstepping increases the complexity of feedback design. Given this, the requirements of shaping system performance constraints, eliminating initial dependence, and reducing data transfer costs together give rise to an interesting and challenging problem. Constructing the time-receding horizon (TRH) and stitching it with the quadratic Lyapunov function (QLF) is the key to constrained tracking. Specifying TRHs as a set of smooth bounds with fixed-time convergence and forcing the system to stabilize within the constrained region before the prescribed settling time provide a sufficient condition for practical finite-time stability (PFS). For relaxing the initial dependence, a tuning function is designed to match the performance constraints under arbitrary system initial conditions. A dual-channel event-triggered mechanism (ETM) is developed to automatically adjust the controller and estimator data flow updates with less transmission burden. By combining a specific inequality with backstepping, uncertainties are overcome without the "complexity explosion" in recursion steps. Finally, simulations demonstrate the effectiveness of the proposed method.

Ultrasonic-assisted resting of Tartary buckwheat dough: Study on its effect and mechanism.

Utilizing natural hypoglycemic ingredients in staple foods is a safe and effective way to improve diabetes. High Tartary buckwheat noodles have garnered research interest due to their hypoglycemic properties. However, increasing the Tartary buckwheat content poses challenges in noodle processing and affects their edible quality. Effective resting is a critical link to improve the processing performance of noodle and edible quality of noodle. Therefore, research was conducted on ultrasound assisted resting of Tartary buckwheat dough (TBD) to explore its feasibility and mechanism in improving the quality of Tartary buckwheat noodle. The results indicated that ultrasound treatment effectively promoted the migration of weakly-bound water towards strongly-bound water, thereby enhancing the gluten protein network structure and increasing the α-helix and ß-sheet contents significantly (p < 0.05). Furthermore, Texture analysis indicated decreased hardness and adhesion, and increased elasticity and stretching distance in the final noodles. Ultrasound-assisted maturation pre-treatment shortens TBD's dough's resting time and improves noodle quality, according to this study.

The effect of three-layer liner on the jet formation and penetration capability of shaped charge jet.

In order to solve the problem of insufficient penetration ability of common liner, a new three-layer liner was proposed. AUTODYN software was used to simulate the efflux forming process of three-layer liner. The influence of four different impact impedance liner materials and different thickness ratio of three-layer liner on efflux performance was studied. In order to study the penetration ability of shaped charge to semi-infinite target plate, the penetration calculation of the target plate was carried out by taking several standoff under different thickness ratios. The optimal thickness ratio of three-layer liner was determined by studying the penetration depth and opening size of the target plate. The results show: By comparing the matching of liner materials with different impact impedances, the head velocity, effective length, total energy, total kinetic energy and effective jet mass of the jet formed when the three-layer liner material is AL 2024, copper and nickel from the outside to the inside are the best. In the analysis of the matching of the thickness ratio of the three-layer liner, the key to the jet forming is the thickness ratio of the outer liner. Within a certain range, the greater the proportion of the thickness of the outer liner, the better the jet forming; when the material of the three-layer liner is AL 2024-copper-nickel from outside to inside, the thickness ratio of the liner is 4/1/1 from outside to inside, and the jet forming is the best. The maximum penetration depth of the shaped charge with a thickness ratio of 1/1/4 from the outside to the inside of the three-layer liner is 395.5 mm, which is 52.3% higher than that of the shaped charge with a double-layer liner. Compared with the shaped charge with single-layer liner, the penetration depth is increased by 62.6%. When the thickness ratio of the three-layer liner is 1/1/4 from the outside to the inside, the maximum entrance diameter of the target plate is 14.3 mm, which is the same as that of the shaped charge with the double-layer liner. Compared with the shaped charge with single-layer liner, the entrance diameter is in-creased by 14.4%.

Advances in Organic-Inorganic Hybrid Latex Particles via In Situ Emulsion Polymerization.

Hybrid latex particles combine the unique properties of inorganic nano/micro particles with the inherent properties of polymers, exhibiting tremendous potential for a variety of applications. Recent years have witnessed an increased interest in the design and preparation of hybrid latex particles with well-defined size, structure and morphology. Due to its simplicity, versatility and environmental friendliness, the in situ (Pickering) emulsion polymerization has been demonstrated to be a powerful approach for the large-scale preparation of hybrid latex particles. In this review, the strategies and applications of in situ (Pickering) emulsion polymerization for the preparation of hybrid latex particles are systematically summarized. A particular focus is placed on the strategies for the preparation of hybrid latex particles with enhanced properties and well-defined core-shell, yolk-shell, multinuclear, raspberry-like, dumbbell-shaped, multipod-like or armored morphologies. We hope that the considerable advances, examples and principles presented in this review can motivate future contributions to provide a deeper understanding of current preparation technologies, develop new processes, and enable further exploitation of hybrid latex particles with outstanding characteristics and properties.

Over-expression of hsa_circ_0088214 suppresses tumor progression by inhibiting Akt signaling pathway in osteosarcoma.

BACKGROUND: To explore the effect of has_circ_0088214 in osteosarcoma cells and corresponding mechanisms. METHODS: Osteosarcoma cell line MG63 and U2OS were selected in this study. Wound-healing and matrigel transwell assays were performed to detect migration and invasion capacities. CCK-8 assay was used to measure cell growth and cisplatin resistance. Cell apoptosis was observed by Hoechst 33342 staining after H2O2 induce. Western Blot was used to detect protein expression level. The rescue experiments were also performed using an Akt activator SC79. RESULTS: Hsa_circ_0088214 was down-regulated in osteosarcoma cells compared to normal osteoblast cells. Over-expression of has_circ_0088214 significantly reduced osteosarcoma cells invasion, migration and resistance to cisplatin, but the apoptotic ratio was increased. The phosphorylation level of Akt could be regulated by hsa_circ_0088214, and rescue experiments proved Akt signaling pathway took part in above biological processes. CONCLUSION: Up-regulation of hsa_circ_0088214 suppresses invasion, migration, cisplatin resistance but promoting apoptosis induced by H2O2 by inhibiting Akt signaling pathway in osteosarcoma.

Autophagy blockage and lysosomal dysfunction are involved in diallyl sulfide-induced inhibition of malignant growth in hepatocellular carcinoma cells.

Diallyl sulfide (DAS), as a major component of garlic extracts, has been shown to inhibit growth of hepatocellular carcinoma cells (HCC), but the underlying mechanism is still elusive. In this study, we aimed to explore the involvement of autophagy in DAS-induced growth inhibition of HepG2 and Huh7 hepatocellular carcinoma cells. We studied growth of DAS-treated HepG2 and Huh7 cells using the MTS and clonogenic assays. Autophagic flux was examined by immunofluorescence and confocal microscopy. The expression levels of autophagy-related proteins AMPK, mTOR, p62, LC3-II, LAMP1, and cathepsin D in the HepG2 and Huh7 cells treated with DAS as well as the tumors formed by HepG2 cells in the nude mice in the presence or absence of DAS were examined using western blotting and immunohistochemistry analysis. We found that DAS treatment induced activation of AMPK/mTOR, and accumulation of LC3-II and p62 both in vivo and in vitro. DAS inhibited autophagic flux through blocking the fusion of autophagosomes with lysosomes. Furthermore, DAS induced an increase in lysosomal pH and inhibition of Cathepsin D maturation. Co-treatment with an autophagy inhibitor (Chloroquine, CQ) further enhanced the growth inhibitory activity of DAS in HCC cells. Thus, our findings indicate that autophagy is involved in DAS-mediated growth inhibition of HCC cells both in vitro and in vivo.

Combined Use of Tranexamic Acid and Rivaroxaban in Posterior/Transforaminal Lumbar Interbody Fusion Surgeries Safely Reduces Blood Loss and Incidence of Thrombosis: Evidence From a Prospective, Randomized, Double-Blind, Placebo-Controlled Study.

STUDY DESIGN: A prospective, randomized, double-blind, placebo-controlled study. OBJECTIVES: There are few studies examining the balance between preventing venous thrombus embolism (VTE) and reducing blood loss in posterior/transforaminal lumbar interbody fusion (PLIF/TLIF) surgeries. This study aimed to evaluate the efficacy and safety of the combine application of TXA and rivaroxaban in patients undergoing PLIF/TLIF and explore relevant factors related to blood loss and VTE. METHODS: Patients in group A which was the control group received 0.9% NaCl solution intravenously. Group B was treated by an intravenous injection of 2 g tranexamic acid (TXA) and the local use of 1 g intraoperatively. Group C was treated the same as group B intraoperatively, and they received 10 mg rivaroxaban qd treatment postoperatively. Eligible patients with an Autar score ≤ 10 were randomly assigned to group A or group B. Patients with an Autar score >10 were allocated into group C. RESULTS: The intraoperative blood loss and postoperative drainage were lower in groups B and C than in group A (P < .001). The blood transfusion rate in group B was lower than that in group A (P < .001), while the incidence of VTE in group C was lower (P < .001). Four factors were found to be positively correlated with obvious total blood loss (P < .05). The data showed that 5 factors were correlated with the development of a thrombus (P < .1). CONCLUSIONS: The combination of TXA and rivaroxaban in PLIF/TLIF patients is safe and effective in reducing D-dimer levels associated with VTE and reducing blood loss.

Clinical application of retrograde sural neurofasciocutaneous flap repair combined with jingulian capsules to treat foot and ankle soft tissue defects.

OBJECTIVES: To observe and analyse the efficacy of retrograde sural neurofasciocutaneous flap repair combined with Jingulian capsules to treat foot and ankle soft tissue defects. METHODS: One hundred and eighty patients with foot and ankle soft tissue defects were enrolled in the study from January 2016 to June 2019 in The Second Department of General Surgery,Baoding First Central Hospital. They were divided into a study group and a reference group with the same case number. The former group was provided combination treatment, i.e. retrograde sural neurofasciocutaneous flap repair combined with Jingulian capsules; the latter group was given vacuum sealing drainage. Then, the treatment outcomes of the two groups were compared. RESULTS: The study group needed fewer dressing changes, less preoperative preparation time and antibiotic use than the reference group, p<0.05. The study group had a significantly lower incidence of wound infections and flap necrosis than the reference group, p<0.05. The study group was significantly superior to the reference group regarding ankle function scores and the pain visual analogue scores (VAS) p<0.05. CONCLUSIONS: Retrograde sural neurofasciocutaneous flap repair combined with Jingulian capsules is a protocol that improves efficacy for soft tissue defects in the foot and ankle, which are worthy of promotion and practice.

Epidemiological profile of 338 traumatic spinal cord injury cases in Shandong province, China.

STUDY DESIGN: Hospital-based retrospective review. OBJECTIVE: To describe the epidemiological characteristics of traumatic spinal cord injury (TSCI) in Liaocheng, China. SETTING: Liaocheng People's Hospital. METHODS: Medical records of 338 persons with TSCI admitted to Liaocheng People's Hospital from 2013 to 2017 were reviewed. The detailed information included gender, age, marital status, occupation, time, etiology, level of injury, ASIA grade, spinal stenosis, concomitant injury, treatment, length of stay. RESULTS: Over this period, the mean age (SD) of persons with TSCI was 50.1 (14.1) years, and the male/female ratio was 3.1:1. 96.4% of all were married. The leading cause was fall, followed by motor vehicle accident (MVA). The most common level of injury was the cervical cord. ASIA grade D and A injuries were the most common, accounting for 48.5 and 29.3% respectively. Among the concomitant injuries, spinal fractures were the most common. Within 24 h, 91.1% of individuals with TSCI arrived hospital, 63.3% of all accepted surgery. CONCLUSION: The results showed that fall and MVA were the two main causes, so we should focused on preventing fall and reducing MVA. Cervical spinal stenosis can increase the risk of TSCI, so education should be provided to this population to raise their risk awareness. In addition, timely treatment was critical for TSCI, but the data showed that rescue process was not standard, so it was necessary for medical staff to popularize professional knowledge.

Mobility gradients yield rubbery surfaces on top of polymer glasses.

Many emerging materials, such as ultrastable glasses1,2 of interest for phone displays and OLED television screens, owe their properties to a gradient of enhanced mobility at the surface of glass-forming liquids. The discovery of this surface mobility enhancement3-5 has reshaped our understanding of the behaviour of glass formers and of how to fashion them into improved materials. In polymeric glasses, these interfacial modifications are complicated by the existence of a second length scale-the size of the polymer chain-as well as the length scale of the interfacial mobility gradient6-9. Here we present simulations, theory and time-resolved surface nano-creep experiments to reveal that this two-scale nature of glassy polymer surfaces drives the emergence of a transient rubbery, entangled-like surface behaviour even in polymers comprised of short, subentangled chains. We find that this effect emerges from superposed gradients in segmental dynamics and chain conformational statistics. The lifetime of this rubbery behaviour, which will have broad implications in constraining surface relaxations central to applications including tribology, adhesion, and surface healing of polymeric glasses, extends as the material is cooled. The surface layers suffer a general breakdown in time-temperature superposition (TTS), a fundamental tenet of polymer physics and rheology. This finding may require a reevaluation of strategies for the prediction of long-time properties in polymeric glasses with high interfacial areas. We expect that this interfacial transient elastomer effect and TTS breakdown should normally occur in macromolecular systems ranging from nanocomposites to thin films, where interfaces dominate material properties5,10.

Suppressed Surface Reorganization in a High-Density Poly(methyl methacrylate) Brush.

A high-density poly(methyl methacrylate) (PMMA) brush (σ = 0.77 chain/nm2) with a lower molecular weight distribution was prepared onto a silicon wafer by surface-initiated atom transfer radical polymerization. The surface of the PMMA brush chains was characterized upon the process of the environmental change, from air to water, using contact angle measurements in conjunction with sum-frequency generation spectroscopy. The surface structure and properties altered less with the changing environment from air to water for the PMMA brush than for a spin-coated film; that is, the extent of surface reorganization could be suppressed by grafting densely-packed chains onto a substrate. Also, the water penetration into the brush surface was inhibited because of the densely packed chain structure.

Diagnostic value of near-infrared or fluorescent indocyanine green guided sentinel lymph node mapping in gastric cancer: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis was conducted to evaluate the diagnostic value of near-infrared (NIR) or fluorescent indocyanine green (ICG) guided sentinel lymph node (SLN) mapping in gastric cancer (GC). METHODS: This meta-analysis was registered at the PROSPERO. Clinical studies were retrieved from the electronic database Pubmed, Embase, Medline, Web of science, and the Cochrane Library. Quality assessment was conducted by an adapted checklist of QUADAS-2. A bivariate mixed-effects model was used to pool the data. Evaluation of articles quality, analysis for publication bias, summary receiver operator characteristic (SROC) curves, and meta-regression were also performed. Subgroup analysis was used to explain the heterogeneities. RESULTS: A total of 13 clinical studies (971 patients) were included. The NIR or fluorescent imaging (FI) involved infrared ray electronic endoscopy (IREE), infrared ray laparoscopic system (IRLS), and FI system. Significant evidence of heterogeneity was found for sensitivity and specificity (I 2 = 91.1% and I 2 = 98.2%), respectively. The pooled SLN sensitivity (Sen), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 0.94(95%CI: 0.80-0.99), 1.00(95%CI: 0.60-1.00), 34.0(95%CI: 9.25-125.29), 0.06(95%CI:0.02-0.22), and 252.50(95%CI: 94.93-671.61), respectively. Area under curve (AUC) of SROC curve was 1.00 (95%CI: 0.99-1.00), and the summary operating point (cut-off value) was SENS = 0.94(95%CI: 0.80-0.99) and SPEC = 1.00(95%CI: 0.60-1.00). Subgroup analysis showed that NIR imaging, imaging performed 20 minutes after intraoperative injection, preoperative injection (especially for FI imaging), stained with immunohistochemistry (IHC) (+hematoxylin-eosin [HE]), cT1 stage, submucosa injection (especially for cT1), mean number of SLN ≥ 5, study size > 26 were associated with higher SLN sensitivity. In terms of ICG concentration, diluted ICG concentration that 0.5 mg/mL (compared with 5 mg/mL) in NIR imaging and 0.05 mg/mL (compared with 0.5 mg/mL) in FI system showed higher sensitivities. However, the differences in tumor diameter (≤30 mm vs >30 mm), gastrectomy methods (opening vs laparoscopy), lymphadenectomy methods (LBD vs pick-up), and publication year (≥2010 vs <2010) did not achieve statistical significance. CONCLUSION: ICG combined with NIR or FI guided SLN mapping is technically feasible for GC. Based on the small sample size evidence, the IREE and IRLS devices may have higher sensitivity than FI in current clinical studies; and there may be an excessive ICG concentration used for current SLN mapping in GC. However, well-designed further studies with large sample size are needed to confirm the best procedure and suitable criteria. MINI-ABSTRACT: This meta-analysis was registered at PROSPERO. Clinical studies on this topic were retrieved from the electronic database Pubmed, Embase, Medline, Web of Science, and the Cochrane Library. The NIR or FI involved IREE, IRLS, and FI techniques. A total of 13 clinical studies (971 patients) were included. Based on the small sample size evidence, NIR or FI ICG guided SLN mapping in GC is technically feasible.

Basolateral CD147 induces hepatocyte polarity loss by E-cadherin ubiquitination and degradation in hepatocellular carcinoma progress.

Hepatocytes are epithelial cells with highly specialized polarity. The disorder and loss of hepatocyte polarity leads to a weakness of cell adhesion and connection, the induction of epithelial-mesenchymal transition, and eventually the occurrence of hepatocellular carcinoma (HCC). Cluster of differentiation 147 (CD147), a tumor-related glycoprotein, promotes epithelial-mesenchymal transition and the invasion of HCC. However, the function of CD147 in hepatocyte depolarization is unknown. Here we identified that CD147 was basolaterally polarized in hepatocyte membrane of liver tissues and HepG2 cells. CD147 not only promoted transforming growth factor-ß1-mediated hepatocyte polarity loss but also directly induced endocytosis and down-regulation of E-cadherin which contributed to hepatocyte depolarization. Overexpression of CD147 induced Src activation and subsequently recruited ubiquitin ligase Hakai for E-cadherin ubiquitination and lysosomal degradation, leading to decreases of partitioning defective 3 expression and ß-catenin nuclear translocation. This signal transduction was initiated by competitive binding of CD147 with integrin ß1 that interrupted the interaction between the Arg-Gly-Asp motif of fibronectin and integrin ß1. The specific antibodies targeting integrin α5 and ß1 reversed the decrease of E-cadherin and partitioning defective 3 levels induced by CD147 overexpression. In human liver tissues, CD147 polarity rates significantly declined from liver cirrhosis (71.4%) to HCC (10.4%). CD147-polarized localization negatively correlated with Child-Pugh scores in human liver cirrhosis (r = -0.6092, P < 0.0001) and positively correlated with differentiation grades in HCC (r = 0.2060, P = 0.004). HCC patients with CD147-polarized localization had significantly better overall survival than patients with CD147 nonpolarity (P = 0.021). CONCLUSION: The ectopic CD147-polarized distribution on basolateral membrane promotes hepatocyte depolarization by activation of the CD147-integrin α5ß1-E-cadherin ubiquitination-partitioning defective 3 decrease and ß-catenin translocation signaling cascade, replenishing a molecular pathway in hepatic carcinogenesis. (Hepatology 2018;68:317-332).

Full-length soluble CD147 promotes MMP-2 expression and is a potential serological marker in detection of hepatocellular carcinoma.

BACKGROUND: As a surface glycoprotein, CD147 is capable of stimulating the production of matrix metalloproteinases (MMPs) from neighboring fibroblasts. The aim of the present study is to explore the role of soluble CD147 on MMPs secretion from hepatocellular carcinoma (HCC) cells, and to investigate the diagnostic value of serum soluble CD147 in the HCC detection. METHODS: We identified the form of soluble CD147 in cell culture supernate of HCC cells and serum of patients with HCC, and explored the role of soluble CD147 on MMPs secretion. Serum CD147 levels were detected by the enzyme-linked immunosorbent assay, and the value of soluble CD147 as a marker in HCC detection was analyzed. RESULTS: Full length soluble CD147 was presented in the culture medium of HCC cells and serum of patients with HCC. The extracellular domain of soluble CD147 promoted the expression of CD147 and MMP-2 from HCC cells. Knockdown of CD147 markedly diminished the up-regulation of CD147 and MMP-2 which induced by soluble CD147. Soluble CD147 activated ERK, FAK, and PI3K/Akt pathways, leading to the up-regulation of MMP-2. The level of soluble CD147 in serum of patients with HCC was significantly elevated compared with healthy individuals (P < 0.001). Soluble CD147 levels were found to be associated with HCC tumor size (P = 0.007) and Child-Pugh grade (P = 0.007). Moreover, soluble CD147 showed a better performance in distinguishing HCC compared with alpha-fetoprotein. CONCLUSIONS: The extracellular domain of soluble CD147 enhances the secretion of MMP-2 from HCC cells, requiring the cooperation of membrane CD147 and activation of ERK, FAK, and PI3K/Akt signaling. The measurement of soluble CD147 may offer a useful approach in diagnosis of HCC.

[Synchronous treatment of heavy metal ions and nitrate by zero-valent iron].

The wastewater which contains bivalent copper and nitrate, bivalent nickel and nitrate, hexavalent chromium and nitrate were simultaneously treated by the zero-valent iron (Fe(0)) system to investigate the feasibility of using Fe(0) for the remediation of contaminated groundwater. The experimental results indicate that nitrate has no obvious effect on the removal of heavy metals, and different heavy metal has different impacts on the removal of nitrate. Bivalent copper accelerates the nitrate removal percentage and the reaction rate. 50 mg x L(-1) bivalent copper made the nitrate removal percentage in 120 min increase from 38.2% to 95.0%, meanwhile made k(obs) of the nitrate reduction increase from 0.004 3 to 0.033 9 min(-1). And the more the concentrations of bivalent copper are, the higher the nitrate removal percentage and the reaction rate are. And it is the bivalent copper that makes the apparent activation energy of the nitrate reduction by Fe(0) decrease from 40.8 k x mol(-1) to 21.1 kJ x mol(-1), which leads to the increase of the reaction rate. When Fe(0) simultaneously treats the wastewater containing bivalent nickel and nitrate, they have no obvious effects on each other. When Fe(0) simultaneously treats the wastewater containing hexavalent chromium and nitrate, the results show the nitrate concentration remains unchanged, and prove that hexavalent chromium decreases the nitrate removal speed.

Remediation of Ni(2+)-contaminated water using iron powder and steel manufacturing byproducts.

Steel manufacturing byproducts and commercial iron powders were tested in the treatment of Ni(2+)-contaminated water. Ni2+ is a priority pollutant of some soils and groundwater. The use of zero-valent iron, which can reduce Ni2+ to its neural form appears to be an alternative approach for the remediation of Ni(2+)-contaminated sites. Our experimental data show that the removal efficiencies of Ni2+ were 95.15% and 94.68% at a metal to solution ratio of 20 g/L for commercial iron powders and the steel manufacturing byproducts in 60 min at room temperature, respectively. The removal efficiency reached 98.20% when the metal to solution ratio was 40 g/L for commercial iron powders. Furthermore, we found that the removal efficiency was also largely affected by other factors such as the pHs of the treated water, the length of time for the metal to be in contact with the Ni(2+)-contaminated water, initial concentrations of metal solutions, particle sizes and the amount of iron powders. Surprisingly, the reaction temperature appeared to have little effect on the removal efficiency. Our study opens the way to further optimize the reaction conditions of in situ remediation of Ni2+ or other heavy metals on contaminated sites.