Tetrahedral Occupied V Ions Enabling Reversible Three-Electron Redox of Cr3+ /Cr6+ in Layered Cathode Materials for Potassium-Ion Batteries.

Reversible three-electron redox of Cr3+ /Cr6+ in layered cathode materials for rechargeable batteries is very attractive in layered cathode materials, which leads to high capacity and energy density for rechargeable batteries. However, the poor reversibility and Cr-ion migration make it very challenging. In this work, by introducing V ions into tetrahedral sites of layer-structured NaCrO2 , reversible three-electron redox of Cr3+ /Cr6+ is realized successfully in NaCr0.92 V0.05 O2 (NCV05) cathode for potassium-ion batteries with a cut-off voltage of 4.0 V. V ions can weaken the attraction of Cr to electrons, leading to enhanced valence change of Cr ions. On the other hand, V in tetrahedral sites can facilitate the reversible migration of Cr between octahedral and tetrahedral sites via coulombic repulsion to realize the reversible redox between Cr3+ and Cr6+ during charge and discharge processes. In addition, V ions can inhibit the phase transition from O3 phase to O'3 phase during the charge process by adjusting the crystal lattices. As a result, the NaCr0.92 V0.05 O2 cathode exhibits a high reversible capacity of 130 mAh g-1 with promising cycle stability and rate capability. The strategy opens new opportunity for developing high-capacity cathode materials for potassium-ion batteries.

Analyses of protein cores reveal fundamental differences between solution and crystal structures.

There have been several studies suggesting that protein structures solved by NMR spectroscopy and X-ray crystallography show significant differences. To understand the origin of these differences, we assembled a database of high-quality protein structures solved by both methods. We also find significant differences between NMR and crystal structures-in the root-mean-square deviations of the C α atomic positions, identities of core amino acids, backbone, and side-chain dihedral angles, and packing fraction of core residues. In contrast to prior studies, we identify the physical basis for these differences by modeling protein cores as jammed packings of amino acid-shaped particles. We find that we can tune the jammed packing fraction by varying the degree of thermalization used to generate the packings. For an athermal protocol, we find that the average jammed packing fraction is identical to that observed in the cores of protein structures solved by X-ray crystallography. In contrast, highly thermalized packing-generation protocols yield jammed packing fractions that are even higher than those observed in NMR structures. These results indicate that thermalized systems can pack more densely than athermal systems, which suggests a physical basis for the structural differences between protein structures solved by NMR and X-ray crystallography.

Budesonide foam for mild to moderate distal ulcerative colitis: A systematic review and meta-analysis.

BACKGROUND AND AIM: Budesonide is a second-generation steroid with prominent topical effects and minimal systemic activity for patients with ulcerative colitis (UC). We perform a systematic review and meta-analysis of randomized placebo-controlled trials to assess the efficacy and safety of budesonide foam in mild-to-moderate distal UC. METHODS: Comprehensive searches were performed to identify all eligible studies. Outcome measures were clinical remission, endoscopic improvement, elimination of rectal bleeding, and adverse events. The risk ratio (RR) with 95% confidence interval (CI) was estimated for each outcome. All statistical analyses were performed in STATA 12.0. RESULTS: Three randomized placebo-controlled trials recruiting 711 patients with mild-to-moderate distal UC were included in this study. No significant bias and heterogeneity was identified. Pooled analyses showed that budesonide foam was significantly superior to placebo for induction of clinical remission (RR = 1.83, 95%CI: 1.41, 2.37; P < 0.001) and endoscopic improvement (RR = 1.44, 95%CI: 1.23, 1.68; P < 0.001), and eliminating rectal bleeding at week 2 (RR = 2.00, 95%CI: 1.50, 2.66; P < 0.001), week 4 (RR = 1.73, 95%CI: 1.42, 2.12; P < 0.001), and week 6 (RR = 1.76, 95%CI: 1.45, 2.14; P < 0.001). No statistically significant difference was observed in the incidence of treatment-related adverse events and therapeutic discontinuation because of adverse events between budesonide foam and placebo. CONCLUSIONS: Budesonide foam is well tolerated and superior to placebo in inducing clinical remission and endoscopic improvement, and eliminating rectal bleeding for mild-to-moderate distal UC.

Computational cell analysis for label-free detection of cell properties in a microfluidic laminar flow.

Although a flow cytometer, being one of the most popular research and clinical tools for biomedicine, can analyze cells based on the cell size, internal structures such as granularity, and molecular markers, it provides little information about the physical properties of cells such as cell stiffness and physical interactions between the cell membrane and fluid. In this paper, we propose a computational cell analysis technique using cells' different equilibrium positions in a laminar flow. This method utilizes a spatial coding technique to acquire the spatial position of the cell in a microfluidic channel and then uses mathematical algorithms to calculate the ratio of cell mixtures. Most uniquely, the invented computational cell analysis technique can unequivocally detect the subpopulation of each cell type without labeling even when the cell type shows a substantial overlap in the distribution plot with other cell types, a scenario limiting the use of conventional flow cytometers and machine learning techniques. To prove this concept, we have applied the computation method to distinguish live and fixed cancer cells without labeling, count neutrophils from human blood, and distinguish drug treated cells from untreated cells. Our work paves the way for using computation algorithms and fluidic dynamic properties for cell classification, a label-free method that can potentially classify over 200 types of human cells. Being a highly cost-effective cell analysis method complementary to flow cytometers, our method can offer orthogonal tests in companion with flow cytometers to provide crucial information for biomedical samples.

Integrated 1550 nm photoreceiver with built-in amplification and feedback mechanisms.

Sensitivity, dynamic range and detection efficiency are among the key figures of merit for 1550 nm wavelength detectors that find applications in communications, sensing, and imaging. Some fundamental material and device limits have added tremendous difficulties for a single device to achieve high sensitivity and dynamic range without significant trade-offs. We present a concept that can potentially overcome this performance bottleneck. Preliminary results have shown a sensitivity of 10 photons (six photons from the quantum limit) and a large dynamic range (in the sense that output increases monotonically with input). The concept opens up a new avenue for detecting single photons in non-Geiger-mode with near 100% detection efficiency.

Label-free Optofluidic Cell Classifier Utilizing Support Vector Machines.

A unique optofluidic lab-on-a-chip device that can measure optically encoded forward scattering signals has been demonstrated. From the design of the spatial pattern, the position and velocity of each cell in the flow can be detected and then a spatial cell distribution over the cross section of the channel can be generated. According to the forward scattering intensity and position information of cells, a data-mining method, support vector machines (SVMs), is applied for cell classification. With the help of SVMs, the multi-dimensional analysis can be performed to significantly increase all figures of merit for cell classification.

[Expression of aquaporin 3 and aquaporin 9 is regulated by oleic acid through the PI3K/Akt and p38 MAPK signaling pathways].

OBJECTIVE: To study the effect of oleic acid (OA) on expression of aquaglyceroporin genes, AQP3 and AQP9, in hepatocyte steatosis and to investigate the underlying molecular mechanisms using an in vitro system. METHODS: HepG2 cells were treated with OA at different concentration to establish in vitro models of nonalcoholic hepatocyte steatosis. The corresponding extents of hepatic steatosis modeling were assessed by oil red O staining and optical density (OD) measurements of the intracellular fat content. The model lines were then treated with inhibitors of the PI3K/Akt and p38 MAPK signaling pathway factors and effects on AQP3/9 expression was measured by real time RT-PCR and western blotting. RESULTS: The fat concentration, indicative of hepatic steatosis, increased in conjunction with increased concentrations of OA (0 less than 250 less than 500 mumol/L). OA exposure also down-regulated AQP3 mRNA and up-regulated AQP9 mRNA levels in a concentration-dependent manner. The most robust changes in expression occurred in response to the 500 mumol/L concentration of OA for both AQP3 (0.47+/-0.18; t = 4.5450, P less than 0.05) and AQP9 (1.57+/-0.21; t = 3.0306, P less than 0.05). Treatment with OA + PI3K pathway inhibitor (LY294004) significantly decreased AQP9 mRNA expression (4.55+/-0.62) as compared to the control group (1.00+/-0.10; t = 9.7909, P less than 0.01), that 500 mumol/L OA group (2.43+/-0.53; t = 4.5018, P less than 0.05), and the LY294002 group (1.90+/-0.16; t = 7.1683, P less than 0.01). Treatment with p38 MAPK pathway inhibitor (SB230580) significantly increased the OA-suppressed level of AQP3 mRNA to the level detected in the control group (1.27+/-0.11; t = 5.7455, P less than 0.01) and decreased the OA-stimulated AQP9 mRNA (0.38+/-0.09; t = 6.5727, P less than 0.01). No significant changes in mRNA expression of AQP3/9 were observed with inhibition of the ERK1/2 and JNK signal transduction pathways. The OA-induced changes in protein expression levels of AQR3 and AQP9 followed a similar trend of the genes. Finally, OA suppressed the level of phosphorylated Akt (from 0.21+/-0.02 to 0.13+/-0.03; t = 3.8431, P less than 0.05) but elevated the level of phosphorylated p38 (from 0.58+/-0.06 to 1.02+/-0.10; t = 12.5289, P less than 0.01). Again, OA treatment produced no significant affect on ERK1/2 and JNK phosphorylation. CONCLUSION: OA down-regulates AQP3 expression by stimulating the p38 MAPK signaling pathway, and up-regulates the AQP9 by blocking the PI3K/Akt pathway and activating the p38 MAPK signaling pathway.

Long Non-Coding RNA ANRIL Regulates Inflammatory Factor Expression in Ulcerative Colitis Via the miR-191-5p/SATB1 Axis.

Ulcerative colitis, an inflammatory bowel disease, manifests with symptoms such as abdominal pain, diarrhea, and mucopurulent feces. The long non-coding RNA (lncRNA) ANRIL exhibits significantly reduced expression in UC, yet its specific mechanism is unknown. This study revealed that ANRIL is involved in the progression of UC by inhibiting IL-6 and TNF-α via miR-191-5P/SATB1 axis. We found that in patients with UC, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly overexpressed in inflamed colon sites, whereas ANRIL was significantly under-expressed and associated with disease severity. The downregulation of ANRIL resulted in the increased expression of IL-6 and TNF-α in LPS-treated FHCs. ANRIL directly targeted miR-191-5p, thereby inhibiting its expression and augmenting SATB1 expression. Moreover, overexpression of miR-191-5p abolished ANRIL-mediated inhibition of IL-6 and TNF-α production. Dual luciferase reporter assays revealed the specific binding of miR-191-5p to ANRIL and SATB1. Furthermore, the downregulation of ANRIL promoted DSS-induced colitis in mice. Together, we provide evidence that ANRIL plays a critical role in regulating IL-6 and TNF-α expression in UC by modulating the miR-191-5p/SATB1 axis. Our study provides novel insights into progression and molecular therapeutic strategies in UC.

An Experimental Study of the Mechanical Properties of Partially Rehabilitated Cable Tunnels.

For buried municipal tunnels-such as cable tunnels and utility tunnels with structural defects-due to the sheltering of the internal pipelines, shelves, and other auxiliary facilities, traditional trenchless rehabilitating methods are not applicable since an intact ring is needed for spraying and lining. In these tunnels, only the exposed area at the crown of the ring can be partly rehabilitated. In this paper, three-edge bearing tests (TEBTs) for partially rehabilitated reinforced concrete (RC) pipe sections are carried out to simulate the case of a municipal tunnel and the effects of different repair materials (cement mortar and epoxy resin) and different dimensional parameters of the liner (lining thickness, lining range) on the partial rehabilitation effect of defective RC pipes are studied. The deforming compatibility of the liner-pipe interface is discussed, and the flexural rigidity of the partially rehabilitated section is calculated. The results show that the load-carrying capacities of partial rehabilitated RC pipes are effectively improved.

[Effects of insulin and LY294002 inhibitors of PI3K on the regulations and expression of aquaporin 9 in normal liver cells].

OBJECTIVES: To explore the effects of insulin on the expression and the regulatory pathway of AQP9 in normal human liver cells. METHODS: Normal human liver cells L02 were cultured and treated with PI3K inhibitor LY294002, AKT inhibitor A-443654, MAPK inhibitors SB2030580 and insulin at different concentrations respectively. The AQP9 mRNA and protein expressions were detected with semi-quantitative RT-PCR and Western blot respectively. RESULTS: The insulin (100 nmol/L approximately 500 nmol/L) treatment decreased the expression of AQP9 in normal human liver cells (P less than 0.05) concentration dependently, and the expression of AQP9 began to reduce from 3 hours of insulin stimulation (P less than 0.05), especially at insulin treatment for 12 hours (P less than 0.05); Incubated with the selective inhibitor of PI3K (LY294002) and AKT (A-443654), the inhibitory effects of insulin on AQP9 expression decreased (P less than 0.05); but it did not change significantly by blocking the MAPK signaling pathway. CONCLUSION: The insulin treatment inhibited the expression of AQP9 and the PI3K/akt signal transduction pathway was involved in the mechanism.

[Efficacy of endoscopic variceal ligation and its correlation with liver function].

OBJECTIVE: To analyze the efficacy of endoscopic variceal ligation and its correlation with liver function. METHODS: 322 patients received EVL (endoscopic variceal ligation) and 34 patients with PDP (pericardial devascularization procedure) were retrospectively analyzed and divided into groups A, B and C. These patients were then subdivided into bleeding and non-bleeding subgroups according to Child-Pugh scores of liver function and history of upper gastrointestinal bleeding. The bleeding rate and mortality were contrasted between EVL and PDP. Liver function, Platelet count, leucocyte count and spleen thickness of before and after ligation were contrasted in EVL. RESULTS: The bleeding rate and mortality were 1.7%, 3.4%, 7.0%; 0%, 5.1%, 8.1% in EVL group and 9.1%, 14.3%, 100.0%; 0%, 9.5%, 50.0% in PDP group, respectively. Variceal obliteration needed means of 2.1+/-0.7, 3.1+/-0.8 and 4.2+/-1.2 sessions in A, B and C ligation groups, respectively (F = 41.2, P is less than 0.01). On subgroup analysis, the numbers of ligation session were 2.6+/-0.7, 3.2+/-0.9 and 4.3+/-1.1 in A, B and C bleeding subgroup (F = 39.3, P value is less than 0.01) and 2.0+/-0.6, 2.7+/-0.6, and 2.9+/-0.4 in A, B and C non-bleeding subgroup, respectively (F = 17.0, P value is less than 0.01). ALT, AST, Platelet count and leucocyte count reduced significantly, spleen thickness increased remarkably in bleeding subgroup after ligation. CONCLUSION: The efficacy of EVL was significantly negatively correlated with liver function and prior to pericardial devascularization procedure. EVL had no effect on liver function but might increase spleen thickness and aggravate hypersplenism. EVL was recommended especially for the bleeding liver cirrhosis patients with Child B and C scores.

Using physical features of protein core packing to distinguish real proteins from decoys.

The ability to consistently distinguish real protein structures from computationally generated model decoys is not yet a solved problem. One route to distinguish real protein structures from decoys is to delineate the important physical features that specify a real protein. For example, it has long been appreciated that the hydrophobic cores of proteins contribute significantly to their stability. We used two sources to obtain datasets of decoys to compare with real protein structures: submissions to the biennial Critical Assessment of protein Structure Prediction competition, in which researchers attempt to predict the structure of a protein only knowing its amino acid sequence, and also decoys generated by 3DRobot, which have user-specified global root-mean-squared deviations from experimentally determined structures. Our analysis revealed that both sets of decoys possess cores that do not recapitulate the key features that define real protein cores. In particular, the model structures appear more densely packed (because of energetically unfavorable atomic overlaps), contain too few residues in the core, and have improper distributions of hydrophobic residues throughout the structure. Based on these observations, we developed a feed-forward neural network, which incorporates key physical features of protein cores, to predict how well a computational model recapitulates the real protein structure without knowledge of the structure of the target sequence. By identifying the important features of protein structure, our method is able to rank decoy structures with similar accuracy to that obtained by state-of-the-art methods that incorporate many additional features. The small number of physical features makes our model interpretable, emphasizing the importance of protein packing and hydrophobicity in protein structure prediction.

Angiotensin-converting enzyme inhibitors improve hepatic steatosis by modulating expression of tumour necrosis factor-alpha, interleukin-6 and adiponectin receptor-2 in rats with type 2 diabetes.

1. Angiotensin-converting enzyme inhibitors (ACEI) are hypotensive drugs that have been shown to prevent Type 2 diabetes mellitus (T2DM) in high-risk individuals. However, in T2DM, the effects of ACEI on hepatic steatosis are not known. The aim of the present study was to examine the effects of ACEI on changes in liver histology and hepatic mRNA expression of adipokines in rats with T2DM. 2. Thirty-six rats were divided into a normal control group, a T2DM group and a fosinopril-treated group. After six weeks of treatment with 5 mg/kg per day fosinopril, an ACEI, changes in liver histology, serum fasting glucose (FG), insulin, triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, adiponectin were evaluated, as was hepatic TNF-alpha, IL-6 and adiponectin receptor-2 (adipoR2) mRNA expression. 3. The degree of hepatic steatosis and inflammation, serum FG, insulin, TG, TC, ALT, TNF-alpha and IL-6 concentrations and hepatic TNF-alpha and IL-6 mRNA expression were significantly higher in rats with T2DM than in normal controls. Serum adiponectin concentrations and hepatic adipoR2 mRNA expression in rats with T2DM were significantly lower than in normal controls. Fosinopril significantly reduced the degree of hepatic steatosis, serum FG, insulin, ALT, TNF-alpha and IL-6 concentrations and hepatic TNF-alpha and IL-6 mRNA expression. Fosinopril significantly increased serum adiponectin concentrations and hepatic adipoR2 mRNA expression. 4. In conclusion, the ACEI improved insulin sensitivity and hepatic steatosis in rats with T2DM by increasing circulating adiponectin and hepatic adipoR2 levels, in addition to reducing pro-inflammatory cytokine levels in the circulation and liver.

Prevalence and related factors of falls among the elderly in an urban community of Beijing.

OBJECTIVE: To understand the prevalence, consequences and risk factors of falls among urban community-dwelling elderly in Beijing. METHODS: A cross-sectional study was conducted in Longtan Community, Beijing. A total of 1512 individuals aged 60 years or over were selected by stratified cluster sampling. Data regarding the frequency of falls in the previous year, as well as circumstances, consequence and related factors of falls were collected from the elderly through face-to-face interviews with questionnaires in their home. RESULTS: The prevalence of falls was 18.0% on the average among 1512 participants, higher in women (20.1%) than in men (14.9%) (P = 0.006), and increased with age (chi2(for trend) = 10.37, P = 0.001). The total rate of falls-induced injuries among the fallers was 37.7%. Falls usually resulted in soft-tissues bruises (58.7%), fear of repeated episodes of falls (58.8%), loss of independence and confidence in movement (35.7%) and even in hip fracture. In addition to the burden of medical care, falls also generated a big economic burden. Occurrence of falls was significantly associated with both intrinsic and extrinsic factors. The related factors of falls in the elderly included age > or = 60-70 years, femininity, less physical activities, fear of future falls, living alone, severely impaired vision, health problem-impacted activities of daily living, chronic diseases (diabetes, hypertension, postural hypotension, stroke sequela, cataract, arthritis, dementia and depression), medications (psychoactive, anti-diabetic), gait imbalance, high bed and faintly-lighted stairway. CONCLUSION: The prevalence of falls among urban community-dwelling elderly in Beijing is closely associated with significant associated with intrinsic and extrinsic factors. Efforts to prevent falls in the elderly should be made at community level.

Void distributions reveal structural link between jammed packings and protein cores.

Dense packing of hydrophobic residues in the cores of globular proteins determines their stability. Recently, we have shown that protein cores possess packing fraction ϕ≈0.56, which is the same as dense, random packing of amino-acid-shaped particles. In this article, we compare the structural properties of protein cores and jammed packings of amino-acid-shaped particles in much greater depth by measuring their local and connected void regions. We find that the distributions of surface Voronoi cell volumes and local porosities obey similar statistics in both systems. We also measure the probability that accessible, connected void regions percolate as a function of the size of a spherical probe particle and show that both systems possess the same critical probe size. We measure the critical exponent τ that characterizes the size distribution of connected void clusters at the onset of percolation. We find that the cluster size statistics are similar for void percolation in packings of amino-acid-shaped particles and randomly placed spheres, but different from that for void percolation in jammed sphere packings. We propose that the connected void regions are a defining structural feature of proteins and can be used to differentiate experimentally observed proteins from decoy structures that are generated using computational protein design software. This work emphasizes that jammed packings of amino-acid-shaped particles can serve as structural and mechanical analogs of protein cores, and could therefore be useful in modeling the response of protein cores to cavity-expanding and -reducing mutations.

[The effectiveness of endoscopic variceal ligation in patients with different grades of liver function].

OBJECTIVE: To evaluate the effectiveness of endoscopic variceal ligation (EVL) in patients with different grades of liver function. METHODS: MELD scores were determined for 156 patients before their EVL operations. After the EVL these patients were followed-up and their survival rates were analyzed. RESULTS: Fifty percent of the patients whose MELDs were less than or equal to 7 survived longer than 45 months after the EVL; in those with MELDs between 7 and 9, 50% of the patients survived 47.34 months; however, the figure for those whose MELD were more than 9 survived only 24.89 months. In the first two groups, 50% of the patient' survival duration was significantly longer than that of the third group. The difference was statistically significant. CONCLUSION: EVL becomes an effective clinical way to treat hemorrhage of esophagus varicose veins. The survival rate for this procedure is directly correlated with the liver function of the patient before the EVL.

Efficacy and safety of transarterial chemoembolization plus sorafenib for early or intermediate stage hepatocellular carcinoma: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: The efficacy and safety of transarterial chemoembolization (TACE) plus sorafenib for patients with hepatocellular carcinoma (HCC) have been explored by many studies, but the results were controversial. Therefore, we performed this meta-analysis of high-quality randomized controlled trials to evaluate the efficacy and safety of TACE plus sorafenib versus TACE monotherapy in the early or intermediate stage HCC. METHODS: Multi-databases were systematically searched to identify all eligible literatures. The hazard ratio (HR) or risk ratio (RR) with 95% confidence intervals (95%CIs) for time to progression (TTP), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and the incidence of treatment-related adverse events (AEs) were pooled using a fixed or random effect model in STATA 12.0. RESULTS: Four randomized controlled trials, including a total of 887 patients with early or intermediate stage HCC, were included in this meta-analysis. The pooled results showed that TACE plus sorafenib significantly improved TTP (HR=0.77, 95% CI: 0.64-0.92; P=0.005). Nevertheless, the OS (HR=0.97, 95% CI: 0.72-1.29; P=0.828), ORR (RR=1.20, 95% CI: 0.88-1.64; P=0.257) and DCR (RR=1.04, 95% CI: 0.90-1.02; P=0.568) were not improved. The incidence of treatment-related AEs was higher in the TACE plus sorafenib. CONCLUSIONS: Evidences from the meta-analysis of high-quality randomized controlled trials indicate that TACE plus sorafenib can significantly improve TTP but not OS, ORR and DCR in early or intermediate stage HCC. In addition, the combination therapy increases the adverse events which usually disturb the treatment progress and should be increased attention.

Expression and clinical significance of aquaglyceroporins in human hepatocellular carcinoma.

Aquaglyceroporins (AQPs) are a subset of the aquaporin family, and are permeable to water and glycerol. The aim of the present study was to determine the expression and clinical significance of three AQPs, AQP3, 7 and 9 in hepatocellular carcinoma (HCC). Fresh HCC and adjacent non­tumorous liver tissues were collected from 68 patients diagnosed with HCC. The expression levels of AQP3, 7 and 9 were detected by reverse transcription­quantitative polymerase chain reaction, western blotting and immunohistochemical analysis. The association between the expression of AQPs and clinicopathological parameters of HCC were investigated. Compared with non­tumorous liver tissue, HCC tissues exhibited a significant (P<0.05) increase in the expression of AQP3 and a concomitant reduction in the expression levels of AQP7 and AQP9, at both the mRNA and protein levels. Immunohistochemistry revealed that AQP9 was dominantly localized on the plasma membrane of hepatocytes, while AQP3 and AQP7 exhibited a predominantly cytoplasmic and nuclear distribution. High expression of AQP3 was significantly (P<0.05) associated with low expression levels of AQP7 and AQP9. High expression of AQP3 was correlated with tumor grade (P=0.017), tumor stage (P=0.010) and lymphatic metastasis (P=0.031). Low expression of AQP7 was correlated with tumor grade (P=0.043). AQP3 was upregulated, and AQP7 and AQP9 were downregulated in HCC. A high expression of AQP3 and low expression of AQP7 was significantly associated with the aggressive features of HCC.

Aquaporin 9 is down-regulated in hepatocellular carcinoma and its over-expression suppresses hepatoma cell invasion through inhibiting epithelial-to-mesenchymal transition.

Aquaporin 9 (AQP9) is the main aquaglyceroporin in the liver. Few studies have been performed regarding the role of AQP9 in hepatocellular carcinoma (HCC). Here, we report the expression and function of AQP9 in HCC tissues and cell lines. We found that AQP9 mRNA and protein levels were down-regulated in HCC tissues and human hepatoma cell lines compared to the para-cancer normal liver tissues and normal hepatocyte line, respectively. In a human HCC SMMC-7721 cell line, over-expression of AQP9 suppressed cell invasion in vitro and xenograft tumor growth in vivo. AQP9 over-expression increased the expression of E-cadherin and decreased the expression of N-cadherin in SMMC-7721 cells and xenografted tumors, which was correlated with decreased levels of phosphoinositide 3-kinase (PI3K) and p-Akt. Conversely, using siRNA to knock down AQP9 over-expression could reverse the phenotype caused by AQP9 over-expression. Our findings suggest that AQP9 is down-regulated in hepatocellular carcinoma and its over-expression suppresses hepatoma cell invasion through inhibiting epithelial-to-mesenchymal transition.

Aquaporin 9 inhibits hepatocellular carcinoma through up-regulating FOXO1 expression.

Aquaporin 9 (AQP9) is the main aquaglyceroporin in the liver. Few studies have been performed regarding the role of AQP9 in liver cancer. Here we report AQP9 expression and function in liver cancer. We found that AQP9 mRNA and protein levels were reduced in human hepatocellular cancer compared to the para-tumor normal liver tissues. Human hepatoma cell line SMMC7721 expressed low basal levels of AQP9. When AQP9 was overexpressed in SMMC7721 cell line, cell proliferation was inhibited due to cell cycle arrest at G1 phase and increased apoptosis. At the molecular level, AQP9 overexpression decreased the protein levels of phosphatidylinositol-3-kinase (PI3K), leading to reduced phosphorylation of Akt. Subsequently, the protein levels of forkhead box protein O1 (FOXO1) were increased, resulting in down-regulation of proliferating cell nuclear antigen (PCNA) expression and up-regulation of caspase-3 expression. AQP9 overexpression inhibited growth of subcutaneously xenografted liver tumors in nude mice. These findings suggest that AQP9 expression is down-regulated in liver cancer compared to the normal liver tissue and restoration of AQP9 expression can inhibit development of liver cancer.