Search

T7 peptide is considered as an antiangiogenic polypeptide. The presents study aimed to further detect the antiangiogenic mechanisms of T7 peptide and determine whether combining T7 peptide and meloxicam (COX-2/PGE2 specific inhibitor) could offer a better therapy to combat hepatocellular carcinoma (HCC). T7 peptide suppressed the proliferation, migration, tube formation, and promoted the apoptosis of endothelial cells under both normoxic and hypoxic conditions via integrin α3β1 and αvβ3 pathways. Cell proliferation, migration, apoptosis, or tube formation ability were detected, and the expression of integrin-associated regulatory proteins was detected. The anti-tumor activity of T7 peptide, meloxicam, and their combination were evaluated in HCC tumor models established in mice. T7 peptide suppressed the proliferation, migration, tube formation, and promoted the apoptosis of endothelial cells under both normoxic and hypoxic conditions via integrin α3β1 and αvβ3 pathways. Meloxicam enhanced the activity of T7 peptide under hypoxic condition. T7 peptide partly inhibited COX-2 expression via integrin α3β1 not αvβ3-dependent pathways under hypoxic condition. T7 peptide regulated apoptosis associated protein through MAPK-dependent and -independent pathways under hypoxic condition. The MAPK pathway was activated by the COX-2/PGE2 axis under hypoxic condition. The combination of T7 and meloxicam showed a stronger anti-tumor effect against HCC tumors in mice. The data highlight that meloxicam enhanced the antiangiogenic activity of T7 peptide in vitro and in vivo.

Aiming at the lack of effective quantitative model to support the analysis of terrorist attacks, a multilayer depth Neural network (NN) Graph convolutional networks (GCN) model (NNGCN) was put forward to realize the classification and early warning of terrorist attacks. The proposed model optimized the traditional GCN with the help of complex NN. The concept of link index was introduced into the NNGCN model. It is combined with the important information between event nodes. The information includes the similarity of events and link probability. Compared with the original unoptimized model, the improved model increased the classification accuracy of terrorist attacks. Because the model uses the node's feature information and the link relationship of graph structure, it can also warn the sudden terrorist attacks effectively.

High pressure processing (HPP) exhibited different effect on polyphenol oxidase (PPO), but the conformational changes was not clear yet. In this study, molecular dynamics simulation combined with spectroscopic experiments were used to explore PPO conformational changes under high pressure at the molecular level. The simulation results showed that high pressure decreased volume and hydrogen bonds, induced changes in active center and movement of loop. Especially, the conformational changes under 200 and above 400 MPa were different. Under 200 MPa, the distance between His 61 and Cu decreased by 0.4 A, active pocket was exposed, substrate channel became larger. However, the distance increased by 6.1 A under 600 MPa, active pocket moved inward, substrate channel became narrower. Docking results of 200 and 600 MPa had the highest and lowest binding affinity, whose T-score was 4.657 and 4.130, respectively. These results were consistent with spectroscopic experiments of PPO after HHP.

Ionic liquids (ILs) and aqueous ionic liquid solutions have been investigated as excellent solvents or catalysts in a few multiphase systems. To optimize the reactor design and operation conditions, it is significant to study the suspended particles behaviors in ILs involved solid–liquid mixing processes. A novel on-line electrical sensing zone (ESZ) method is developed to achieve the measurement of local solids concentration in aqueous [Bmim]BF4 conductive solutions. The suspension degrees of solid particles stirred by different impellers at varied agitation speeds have been obtained. The mean fluid velocities and turbulent fluctuating velocities close to the bottom of the unbaffled tanks have been determined by stereoscopic particle image velocimetry (SPIV). The results showed that the aqueous [Bmim]BF4 solutions are more efficient on solids than normal saline solution. Radical flow impeller with wider blades at C/T = 0.2 presents its better performance on solids suspension. The variations of solids suspension curves are more consistent with that of mean radial velocities at axial height of z/H = 0.99. It indicated that the solids suspension in unbaffled stirred tanks is mainly related to the mean flow rather than to turbulent fluctuations.

A new multifunctional β-cyclodextrin-sodium xanthogenate (β-CDX) was successfully synthesized by a one-step process and applied to remove Pb(II) from aqueous solutions. The characteristics and chelation mechanisms of β-CDX were investigated by Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy, and the influences of various operating parameters such as pH (lime dosage), the order of the additions, β-CDX dosage, and the initial concentration of Pb(II) on the removal capacity of β-CDX and the characteristics of the products were systematically evaluated. The results demonstrated that the optimal removal effect for Pb(II) was achieved when β-CDX was used rather than using lime alone. In addition, it was more effective to add β-CDX to the working solutions prior to adding the lime than adding β-CDX after the lime. The use of 0.05 g/L of β-CDX was effective for the removal of Pb(II) according to the residual concentration when the initial concentration was 100 mg/L at different pH values. The maximum removal rate of the Pb(II) ions was 98% for all initial concentrations and the products were larger (size = 137.9 μm) and looser (Df = 1.73) at an optimum pH range from 9 to 12. The characterization results confirmed that the RC(S)SNa in the β-CDX was the main contributor to the chelation of the Pb(II). These properties of β-CDX make it a promising compound for the treatment of wastewater contaminated by hazardous metal ions.

Purpose: Systemic therapy has often been used for patients with advanced hepatocellular carcinoma (HCC). However, due to drug resistance, the use of cytotoxic chemotherapy in the treatment of patients with advanced HCC has typically demonstrated low response rates. Secretory clusterin (sCLU) is expressed in aggressive late-stage tumors and associated with resistance to chemotherapy, including that in HCC cases. The present research aimed to investigate the biological role of sCLU in HCC. Methods: sCLU expression in HCC and normal tissues was examined using immunohistochemical staining, followed by analysis of the correlation between sCLU expression and clinical indicators. In addition, the role and internal mechanism of sCLU in cell proliferation and apoptosis were investigated in HCC cells. Results: sCLU expression was significantly upregulated in HCC tissues; and was associated with histological grade and poor overall survival. The levels of sCLU were significantly increased in Bel7402, SMMC7721 and resistant HCC cells (Bel7404-OR). Inhibiting the activity of sCLU enhanced the chemosensitivity of Bel7402 and SMMC7721 cells. Downregulation of sCLU could increase the expression of Gadd45a in HCC cells. Overexpression of sCLU contributed to drug resistance in Bel7402, SMMC7721 and Bel7404-OR cells; whereas, overexpression of Gadd45a alone overcame drug resistance in the cells above. No significant expression changes of sCLU and Gadd45a were observed in HCC cells after the interference of a selective inhibitor of the PI3K/Akt signaling pathway. However, regulation of the expression of Gadd45a could influence the phosphorylation level of Akt; and further regulate the expression of Bcl-2 and Bax proteins involved in the mitochondrial apoptosis pathways. Conclusions: The results demonstrate that sCLU/Gadd45a/PI3K/Akt signaling represents a novel pathway that could regulate drug resistance in a one-way manner in HCC cells.

In2S3-decorated MoO3@MoS2 (In/MoO3@MoS2) composites were fabricated via the in-situ sulfurization of nonthermal plasma for the visible light driven photoreduction of CO2 to CH4 and CO. In2S3 can efficiently enhance the photocatalytic activity of In/MoO3@MoS2 in comparison to h-MoO3. The optimal 3-In/MoO3@MoS2 with a In content of 1.33% and the MoS2 thickness of around 10 nm presents the superior conversion efficiency of CO2, of which the yield of CH4 and CO are 29.4 and 35.6 μmol g−1 h−1, respectively. However, the long-term photo-corrosion induced to the declining yield of CH4 and CO after three cycle times. The introduction of In2S3 into MoO3@MoS2 as well as the nonthermal plasma induced S-rich sites and O vacancies is likely to provide the sufficient active sites for promoting CO2 activation and the efficient junction interface for achieving the transfer and separation of charge carriers.

The characterization of soluble polyphenol oxidase (sPPO) and membrane-bound (mPPO) from ‘Lijiang snow’ peach was compared, and the inactivation effects by thermal treatment ranging from 45 to 85 °C and high-pressure processing at 550 MPa for 10–50 min were investigated. sPPO and mPPO both showed optimum activity at pH 7.0, while another optimum pH at 5.0 was observed for mPPO. The optimum temperatures for sPPO and mPPO were 30 °C and 50 °C, respectively. The optimum substrate of sPPO was caffeic acid, while mPPO showed the highest activity against 4-methylcatechol. All inhibitors showed poorer inhibitory effects on mPPO compared with sPPO. According to kinetic parameters, sPPO and mPPO were well described by the first-order model and the fractional-conversion model, respectively. The activity of sPPO was activated after HPP at 550 MPa for 20–50 min, while mPPO was more stable under the treatment conditions investigated.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies. The Yes-associated protein-1 (YAP) plays a critical role in cell proliferation, apoptosis and angiogenesis. Verteporfin is a photosensitizer used in photodynamic therapy and also a small molecular inhibitor of the Hippo-YAP pathway. However, little is known about whether verteporfin could inhibit YAP activity in PDAC cells. Our present results showed that verteporfin suppressed the proliferation of human PDAC PANC-1 and SW1990 cells by arresting cells at the G1 phase, and inducing apoptosis in dose- and time-dependent manners. Verteporfin also inhibited the tumor growth on the PDAC xenograft model. Treatment with verteporfin led to downregulation of cyclinD1 and cyclinE1, modulation of Bcl-2 family proteins and activation of PARP. In addition, verteporfin exhibited an inhibitory effect on angiogenesis and vasculogenic mimicry via suppressing Ang2, MMP2, VE-cadherin, and α-SMA expression in vitro and in vivo. Mechanism studies demonstrated that verteporfin impaired YAP and TEAD interaction to suppress the expression of targeted genes. Our results provide a foundation for repurposing verteporfin as a promising anti-tumor drug in the treatment of pancreatic cancer by targeting the Hippo pathway.

The P18 peptide is a functional fragment of pigment epithelial-derived factor (PEDF), which is an endogenic angiogenesis inhibitor. This study sought to determine the anti-angiogenic bioactivity of the P18 peptide in hepatocellular carcinoma (HCC) and to elucidate the underlying mechanism. Xenograft tumour growth assays demonstrated the P18 peptide suppressed angiogenesis of HCC in vivo. Wound healing, Transwell and Matrigel-culture assays indicated that the P18 peptide inhibited the cell migration and tube formation of endothelial cells (ECs) in vitro. Cell viability and apoptosis assessed by Cell Counting Kit-8 (CCK-8) and flow cytometry assays suggested that the P18 peptide inhibited angiogenesis by inducing apoptosis of ECs. Angiogenesis- and signal transduction-associated molecules analysed by western blot demonstrated that the P18 peptide targets vascular endothelial cell growth factor receptor 2 (VEGFR2) on ECs. In conclusion, by inhibiting the phosphorylation of VEGFR2, the P18 peptide modulates signalling transduction between VEGF/VEGFR2 and suppresses activation of the PI3K/Akt cascades, leading to an increase in mitochondrial-mediated apoptosis and anti-angiogenic activity. This bioactivity of the P18 peptide may represent a novel therapeutic strategy for the treatment of HCC.

Session-based recommendation is used to generate a session recommendation list for the current user according to the existing session information. Most of the existing session-based recommendation models with deep learning only focus on the session information of users, rarely consider the interaction recommendation between similar users, and ignore the user's interest orientation, so the accuracy of the session-based recommendation still has space to improve. To solve above problems, an application model of GNN in session recommendation was proposed. Firstly, take the item's number and order accessed by user session as the basis of clustering, k-means algorithm was used to cluster the sessions to generate k similar sessions clusters. Secondly, choose the appropriate atomic interest on the basis of session clustering to expand user's session length and strengthen user's interest orientation. Thirdly, train the enhanced user sessions by using graph neural network to obtain the latent vector of items, and predict the probability of item being clicked according to the items and the latent vector of the given session, and then generate session recommendation list. Finally, the proposed model is compared with other session recommendation models in YOOCHOOSE and DIGINETICA dataset. The experimental results show that the proposed model has higher recommendation accuracy.

The T7 peptide, an active fragment of full-length tumstatin [the non-collagenous 1 domain of the type IV collagen α3 chain, α3 (IV) NC1], has exhibited potential antitumor effects in several types of cancer cells. However, the mechanism underlying its action against human hepatocellular carcinoma (HCC) remains unclear. The present study aimed to investigate the role of autophagy in T7 peptide-induced cytotoxicity in HCC cells in vitro and in vivo. The results revealed that the T7 peptide significantly reduced cell viability and induced cell cycle arrest in HCC cells. The T7 peptide induced apoptosis in HCC cells through upregulation of Bax, Fas, and Fas ligand, and through upregulation of the anti-apoptotic protein Bcl-2. In addition, treatment with the T7 peptide induced protective autophagy in HCC cells. Blocking autophagy by 3-methyladenineor bafilomycin A1 enhanced T7 peptide-induced apoptosis. Furthermore, co-treatment with MK-2206 (an Akt specific inhibitor) or rapamycin (an inhibitor of mTOR) enhanced T7 peptide-induced autophagy, whereas co-treatment with insulin (an activator of the Akt/mTOR signaling pathway) alleviated T7 peptide-induced autophagy, which suggested that the T7 peptide may induce autophagy activation via inhibition of the Akt/mTOR signaling pathway. Taken together, the present results demonstrated that suppression of autophagy potentiated the cytotoxic effects of the T7 peptide, and suggested that the T7 peptide may serve as a potential alternative compound for HCC therapy.

Online microparticle detection is of utmost importance for industrial production. This paper proposes a signal processing and feature identification strategy to achieve particle size statistics for online measurement in a three-phase stirred tank reactor based on the electrical sensing zone (ESZ) method. Signal denoising and de-interference are achieved using the wavelet soft threshold method combined with mathematical morphological filtering. Pulse selection is implemented using pulse width limiting conditions. The key features that distinguish the pulse waveforms are defined based on the differences in the motion characteristics of the different types of particles through the aperture. Finally, the unsupervised classification algorithm balanced iterative reducing and clustering using hierarchies clustering is employed to distinguish the pulsed features between hard particles and bubbles. The results show that the particle size distribution identified by this strategy agrees with offline measurements indicating the effectiveness of the scheme. The effects of electromagnetic noise and the interference of small bubbles that approximate the particle size in solution in the online, in-situ measurement task are solved. This study scheme has a guiding and facilitating role in applying the ESZ principle to the industrial online measurement environment.

Recurrence and metastasis are the two leading causes of poor prognosis of hepatocellular carcinoma (HCC) patients. Cyclooxygenase (COX)-2 is overexpressed in many types of cancers including HCC and promotes its metastasis. Meloxicam is a selective COX-2 inhibitor that has been reported to exert an anti-proliferation and invasion/migration response in various tumors. In this study, we examined the role of meloxicam on HCC cell proliferation and migration and explored the molecular mechanisms underlying this effect. We found that meloxicam inhibited HCC cell proliferation and had a cell cycle arrest effect in human HCC cells. Furthermore, meloxicam suppressed the ability of HCC cells expressing higher levels of COX-2 and prostaglandin E2 (PGE2) to migration via potentiating expression of E-cadherin and alleviating expression of matrix metalloproteinase (MMP)-2 and -9. COX-2/PGE2 has been considered to activate the β-catenin signaling pathway which promotes cancer cell migration. We found that treatment with PGE2 significantly enhanced nuclear accumulation of β-catenin and the activation of GSK3β which could be reversed by meloxicam in HCC cells. We also observed that HCC cell migration and upregulation of the level of MMP-2/9 and downregulation of E-cadherin induced by PGE2 were suppressed by FH535, an inhibitor of β-catenin. Taken together, these findings provide a new treatment strategy against HCC proliferation and migration.

CeO2-modified Mg-Al layered double oxide (CeO2/Mg-Al LDO) nanosheets were prepared via a one-pot hydrothermal route for visible-light induced photocatalytic reduction of Cr(VI). The addition of CeO2 can enhance the visible light harvesting capacity and the separation of charge carriers of CeO2/Mg-Al composites due to the surface-defect structures of Ce(III)/Ce(IV) couple and oxygen vacancies. The photocatalytic activity of CeO2/Mg-Al is affected by CeO2 content, Cr(VI) concentration, co-existing inorganic ions, and initial pH value. Among these obtained composites, CeO2/Mg-Al-2 with a nominal Mg/Al molar ratio of 2:1 and CeO2 content of 6.0 wt% presents the best photocatalytic efficiency and stability. The removal efficiency of Cr(VI) in the CeO2/Mg-Al-2-assisted photocatalytic system is varied from 96.76% to 92.87% after five cycle times. The quenching behaviors of active species and the possible photocatalytic mechanism of CeO2/Mg-Al-2 were proposed for the conversion of Cr(VI) into Cr(III) in the visible light region.

The timely and effective treatment for severe acute pancreatitis (SAP) is favorable to prognosis. Decompression of the bile duct might be a feasible way to decrease the progression of SAP. The present study investigated the effects of sustained bile external drainage on organs injury caused by SAP in Sprague-Dawley (SD) rats and the mechanisms involved. A total of 72 female SD rats weighting 190-230 g were randomly divided into four groups (n=18): Sham operation group (SOG), SOG + bile drainage group (BDG), SAP group, and SAP + BDG. Sodium taurocholate solution (4%; 1 mg/kg body weight) was used to set up SAP model via injection of retrograde puncture of biliopancreatic duct through the duodenum. A cannula was inserted into the bile duct and fixed externally to establish BDG model. At each time points (t=3, 6, 12; n=6), tissues from the liver, lung, and pancreas, and blood samples were collected. Serum amylase (AMY) was analyzed in all the samples. The levels of tumor necrosis factor-α (TNF-α), heme oxygenase-1 (HO-1), interleukin-10 (IL-10) and high mobility group box 1 (HMGB1) were detected by ELISA. Hematoxylin-eosin staining was performed to observe the histopathological changes, and nuclear transcription factor (NF)-κB-p65 levels in the pancreas were analyzed by western blotting. The data indicated that BDG alleviated the SAP progression and multiple organs injuries. Meanwhile, the histopathological changes of the pancreas, liver, and lungs were improved by BDG. BDG decreased the pathological scores of pancreas significantly (P

Pancreatic ductal adenocarcinoma is one of the most lethal cancers. The Hippo pathway is involved in tumorigenesis and remodeling of tumor microenvironments. Hypoxia exists in the microenvironment of solid tumors, including pancreatic ductal adenocarcinoma and plays a vital role in tumor progression and metastasis. However, it remains unclear how hypoxia interacts with the Hippo pathway to regulate these events. In this study, expressions of yes-associated protein 1 and hypoxia-inducible factor-1α were found to be elevated in pancreatic ductal adenocarcinoma samples compared with those in matched adjacent non-tumor samples. Moreover, hypoxia-inducible factor-1α expression was positively correlated with yes-associated protein 1 level in pancreatic ductal adenocarcinoma tissues. The higher expression of nuclear yes-associated protein 1 was associated with poor histological grade and prognosis for pancreatic ductal adenocarcinoma patients. In vitro, yes-associated protein 1 was highly expressed in pancreatic ductal adenocarcinoma cells. Depletion of yes-associated protein 1 inhibited the invasion of pancreatic ductal adenocarcinoma cells via downregulation of Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-13, and upregulation of E-cadherin. In addition, hypoxia promoted the invasion of pancreatic ductal adenocarcinoma cells via regulating the targeted genes. Hypoxia also deactivated the Hippo pathway and induced yes-associated protein 1 nuclear translocation. Furthermore, depletion of yes-associated protein 1 or hypoxia-inducible factor-1α suppressed the invasion of pancreatic ductal adenocarcinoma cells under hypoxia. Mechanism studies showed that nuclear yes-associated protein 1 interacted with hypoxia-inducible factor-1α and activated Snail transcription to participate in epithelial–mesenchymal transition–mediated and matrix metalloproteinase–mediated remodeling of tumor microenvironments. Collectively, yes-associated protein 1 is an independent prognostic predictor that interacts with hypoxia-inducible factor-1α to enhance the invasion of pancreatic cancer cells and remodeling of tumor microenvironments. Therefore, yes-associated protein 1 may serve as a novel promising target to enhance therapeutic effects for treating pancreatic cancer.

Sorafenib (SOR) is a promising treatment for advanced hepatocellular carcinoma (HCC). However, the precise mechanisms of toxicity and drug resistance have not been fully explored and new strategies are urgently needed for HCC therapy. Meloxicam (MEL) is a selective cyclooxygenase-2 (COX-2) inhibitor which elicits antitumor effects in human HCC cells. In the present study, we investigated the interaction between MEL and SOR in human SMMC‑7721 cells and the role endoplasmic reticulum (ER) stress exerts in the combination of SOR with MEL treatment-induced cytotoxicity. Our results revealed that the combination treatment synergistically inhibited cell proliferation and enhanced apoptosis. Furthermore, the combination treatment enhanced ER stress-related molecules which involved in SMMC-7721 cell apoptosis. GRP78 knockdown by siRNA or co-treatment with MG132 significantly increased this combination treatment-induced apoptosis. In addition, we found that the combination treatment suppressed tumor growth by way of activation of ER stress in in vivo models. We concluded that the combination of SOR with MEL treatment-induced ER stress, and eventually apoptosis in human SMMC-7721 cells. Knockdown of GRP78 using siRNA or proteosome inhibitor enhanced the cytotoxicity of the combination of SOR with MEL-treatment in SMMC-7721 cells. These findings provided a new potential treatment strategy against HCC.

Objectives Meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated to exert anti-tumour effects against various malignancies. However, up to now, mechanisms involved in meloxicam anti-hepatocellular carcinoma effects have remained unclear. Materials and methods Cell viability and apoptosis were assessed by CCK-8 and flow cytometry. Endoplasmic reticulum (ER) stress and autophagy-associated molecules were analysed by western blotting and immunofluorescence assay. GRP78 and Atg5 knock-down by siRNA or chemical inhibition was used to investigate cytotoxic effects of meloxicam treatment on HCC cells. Results We found that meloxicam led to apoptosis and autophagy in HepG2 and Bel-7402 cells via a mechanism that involved ER stress. Up-regulation of GRP78 signalling pathway from meloxicam-induced ER stress was critical for activation of autophagy. Furthermore, autophagy activation attenuated ER stress-related cell death. Blocking autophagy by 3-methyladenine (3-MA) or Atg5 siRNA knock-down enhanced meloxicam lethality for HCC by activation of ER stress-related apoptosis. In addition, GRP78 seemed to lead to autophagic activation via the AMPK–mTOR signalling pathway. Blocking AMPK with a chemical inhibitor inhibited autophagy suggesting that meloxicam-regulated autophagy requires activation of AMPK. Conclusions Our results revealed that both ER stress and autophagy were involved in cell death evoked by meloxicam in HCC cells. This inhibition of autophagy to enhance meloxicam lethality, suggests a novel therapeutic strategy against HCC.

Disrupting tumor angiogenesis serves as an important strategy for cancer therapy. Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has exhibited potent anti-angiogenic activity. However, the molecular mechanisms underlying this effect have not been fully understood. The present study aimed to investigate the role of DHA on endothelial cell proliferation, the essential process in angiogenesis. Human umbilical vein endothelial cells (HUVECs) treated with DHA were examined for proliferation, apoptosis and activation of the extracellular signal-regulated kinase (ERK) signaling pathway. Proliferation of HUVECs was inhibited by 20 µM DHA without induction of apoptosis. DHA also reduced the phosphorylation of ERK1/2, and downregulated the mRNA and protein expression of ERK1/2 in HUVECs. In addition, DHA suppressed the transcription and protein expression of ERK1/2 downstream effectors c-Fos and c-Myc. Electrical cell-substrate impedance sensing real-time analysis demonstrated that ERK signaling inhibitor PD98059 comprises the anti-proliferative effects of DHA. Thus, DHA inhibits endothelial cell proliferation by suppressing the ERK signaling pathway. The present study strengthened the potential of DHA as an angiogenesis inhibitor for cancer treatment.

Sorafenib is a type of multikinase inhibitor that exhibits antiangiogenic and antiproliferative effects; in addition, sorafenib is a unique first-line drug recommended for the treatment of advanced hepatocellular carcinoma (HCC). However, the effectiveness of HCC treatment remains poor due to acquired drug resistance. It has been suggested that hypoxia, induced as a results of the antiangiogenic effects of sustained sorafenib treatment, may be an important factor in sorafenib resistance. The transcription factor hypoxia-inducible factor (HIF)-2α has been reported to be associated with cell proliferation under hypoxic conditions; therefore, it was hypothesized that hypoxia may enhance tumor cell proliferation via this mechanism. The present study aimed to evaluate whether the knock-down of HIF-2α was able to enhance the therapeutic efficacy of sorafenib in order to effectively treat HCC. The results demonstrated that hypoxia protected HCC cells against sorafenib; however, short hairpin RNA-HIF-2α transfection in combination with sorafenib treatment exhibited a significantly synergistic effect against HCC cell proliferation. In addition, HCC cells acquired increased β-catenin/C-Myc expression, which enhanced proliferation under hypoxic conditions; however, targeted knock-down of HIF-2α or C-Myc markedly decreased cell proliferation in HCC cells. In conclusion, the results of the present study indicated that the targeted knock-down of HIF-2α in combination with sorafenib may be a promising strategy for the treatment of HCC.

Angiogenesis is required for the invasion, metastasis and chemoresistance of tumor cells. In addition to vascular endothelial cell growth factor (VEGF), angiopoietin-2 (Ang2) is considered to be a promising target for anti-angiogenic therapy. The T7 peptide, an active fragment of full-length tumstatin [the noncollagenous 1 domain of the type IV collagen α3 chain, α3(IV)NC1], has equivalent anti-angiogenic activity to that of full-length tumstatin. This study aimed to explore the mechanisms of the T7 peptide in the regulation of Ang2 expression in endothelial cells (ECs) as well as inhibition of angiogenesis and invasion of hepatocellular carcinoma cells. We also examined the role of autophagy in angiogenesis. Human umbilical vein endothelial cells (HUVECs) were incubated with endothelial cell medium (ECM)-2 in a hypoxia chamber to mimic hypoxic conditions. The recombinant T7 peptide inhibited the cell viability, tube formation and induced apoptosis of the HUVECs. The T7 peptide downregulated the protein expression of Ang2 by inhibiting phosphorylation of AKT under hypoxic conditions. The migration of HUVECs and invasion of HepG2 cells were inhibited by the T7 peptide via inhibition of Ang2 expression. EC autophagy was induced by the T7 peptide. Inhibition of autophagy enhanced the anti‑angiogenic activity of the T7 peptide by increasing EC apoptosis. In vivo, immunohistochemistry of VE-cadherin and CD31 showed that angiogenesis was decreased significantly by the T7 peptide in a nude mouse xenogeneic tumor model. In conclusion, the T7 peptide inhibited angiogenesis and exerted its antitumor effects by inhibition of Ang2, phosphorylation of AKT and matrix metalloproteinase-2 (MMP-2) regulated by Ang2. Furthermore, inhibition of autophagy may significantly enhance the anti-angiogenic activity of the T7 peptide.

A method for the detection of dichloromethane (DCM) in waste water was developed by using head-space gas chromatography with FID detection. The calibration curve was linear in three orders of magnitude range of DCM levels and the linear correlation coefficient was 0.9995. The limit of detection was 0.004 mg/l and the limit of quantitation was 0.01 mg/l. The system and method precision were both accord with the requirement. The method, practiced in the quantitative determination of DCM in waste water, solved many problems as such and high water content in sample. Many impurities which impacted the detection of DCM were separated visibly.

Let E be a real uniformly smooth Banach space and A : D(A) ⊆ E → 2E be a m-accretive mapping which satisfies a linear growth condition of the form ||u|| ≤ C (1 + ||x||) for some constant C ≫ 0 and for all x ∈ E and u ∈ Ax, z ∈ D(A) be an arbitrary element. Suppose A−1 0 ≠ o. The sequence {x n } ⊂ D(A) is generated from arbitrary x 0 ∈ D (A) by x n +l ∈ x n -λ n (u n + θ n (x n - z)), u n ∈ Ax n , n ≥ 0, where {λ n } and {θ n { are acceptably paired, then {x n { converges strongly to x* ∈ A−(0). As its application, we have deduced a strong convergence theorem for the iterative algorithm of fixed points for continuous pseudocontractions.