Expression of serine protease SNC19/matriptase and its inhibitor hepatocyte growth factor activator inhibitor type 1 in normal and malignant tissues of gastrointestinal tract

AIM： To provide the expression profile of serine protease SNC19/matriptase and its inhibitor hepatocyte growth factor activator inhibitor type 1 （HAI-1） in normal and malignant tissues of gastrointestinal tract at mRNA level for further study on their correlations with tumor progression and metastasis. METHODS： Total RNAs were prepared from 37 samples of colorectal cancer tissues, 40 samples of gastric cancer tissues, and their adjacent normal tissues. The expression of SNC19/matriptase and HAI-1 in these samples was detected by real-time fluorescent quantitative PCR using glyceraldehyde-3-phosphate dehydrogenase as internal standard, and the clinical significance for the correlation with clinicopathological parameters was evaluated. RESULTS： In gastric cancer tissues the expression of HAI-1 and SNC19/matriptase was significantly lower than that in the corresponding adjacent normal tissues （Z = -3.280, P= 0.006; Z= -4.651, P= 0.000）. HAI-1：SNC19/matriptase ratio showed no difference between normal and malignant tissues （P〉0.05）. Analysis of clinicopathological parameters showed decreased expression of HAI-1 and HAI-1：SNC19/ matriptase ratio associated with stage Ⅲ/Ⅳ gastric tumors as compared to stage Ⅰ/Ⅱ ones （Z= -2.140, P= 0.031; Z = -2.155, P = 0.031）, and with lymph node-positive gastric cancer tissues as compared to lymph node-negative ones （Z = -2.081, P = 0.036; Z= -2.686, P = 0.006）. The expression of SNC19/matriptase had no relationship with stages and lymph node metastasis （P〉0.05）. The expression of HAI-1 and HAI-1：SNC19/matriptase ratio increased in well-differentiated gastric cancer tissues, but there was no statistical significance （P〉0.05）. The difference of SNC19/matriptase expression was not significant in gastric cancer tissues of different histological differentiation status （P〉0.05）. In colorectal cancer tissues, the expression of HAI-1 and SNC19/matriptase was also markedly lower than that in their adjacent normal tissues （Z= -3.100, P = 0.002; Z= -2.731, P = 0.006）, whereas HAI-1：SNC19/matriptase ratio showed no difference. Decreased expression of HAI-1 was associated with increased invasive depth and lymph node metastasis, but there was no statistical significance （P〉0.05）. The difference of SNC19/matriptase expression and HAI-1： SNC19/matriptase ratio was not significant in different stages and different lymph node metastasis status （P〉0.05）. The expression of SNC19/matriptase, HAI-1 or HAI-1： SNC19/matriptase ratio showed no difference in colorectal cancer tissues of different histological differentiation status （P〉0.05）. CONCLUSION： The expressions of SNC19/matriptase and its inhibitor HAI-1 are decreased in gastrointestinal cancer tissues compared to their normal counterparts, and the decreased expression of HAI-1 may correlate with invasion and lymph node metastasis. The possible mechanisms involved need to be further investigated.

Interference of Y-27632 on the signal transduction of transforming growth factor beta type 1 in ocular Tenon capsule fibroblasts

AIM: To investigate the interfering effect of Y-27632, a ROCK-I selective inhibitor, on the signal transduction pathway of transforming growth factor-beta 1 (TGF-beta 1) in ocular Tenon capsule fibroblasts (OTFS) in vitro. METHODS: After OTFS from passages 4 to 6 47 vitro were induced by TGF-beta 1 and then treated by Y-27632, the changes of the OTFS cell cycles were analyzed via flow cytometry, and the proteins expression of the alpha -smooth muscular actin (alpha -SMA), connective tissue growth factor (CTGF), collagen I were calculated by Western blot. After OTFS treated by the different concentrations of Y-27632, the expression levels of the alpha -SMA, CTGF and collagen I mRNA were assayed by RT-PCR. RESULTS: Y-27632 had no markedly effect on the OTFS cell cycles. After treated by TGF-beta 1, OTFS in G1 period significantly increased. The cell cycles distribution by both TGF-beta 1 and Y-27632 had no remarkable difference from that in control group. Y-27632 significantly inhibited the proteins expressions of both alpha -SMA and CTGF, while to some extent inhibited that of collagen I. TGF-beta 1 significantly promoted the proteins expressions of alpha -SMA, CTGF and collagen I. After OTFS treated by both TGF-beta 1 and Y-27632, of alpha -SMA, the protein expression was similar with that in control group (P=0.066>0.05), but the protein expression of CTGF or collagen I, respectively, was significantly different from that in control group (P=0.000<0.01). The differences of expressions of the alpha -SMA, CTGF and collagen I mRNA in 30, 150, 750 mu mol/L Y-27632 group were statistically significant, compared with those in control group, respectively (alpha -SMA, P=0.002, 0.000, 0.000; CTGF, P=0.014, 0.002, 0.001; collagen I,P=0.003, 0.002, 0.000). CONCLUSION: Blocking the Rho/ROCK signaling pathway by using of Y-27632 could inhibit the cellular proliferation and the expression of both CTGF and alpha -SMA whatever OTFS induced by TGF-beta 1 or not. Y-27632 suppressed the expression of collagen I mRNA without induction.

Human epidermal growth factor receptor type 2 protein expression in Chinese metastatic prostate cancer patients correlates with cancer specific survival and increases after exposure to hormonal therapy

Aim： To investigate human epidermal growth factor receptor type 2 （HER2） protein expression and gene amplification in Chinese metastatic prostate cancer patients and their potential value as prognostic factors. Methods： Immunohistochemistry （IHC） was performed to investigate HER2 protein expression in prostate biopsy specimens from 104 Chinese metastatic prostate cancer patients. After 3-11 months of hormonal therapy, 12 patients underwent transurethral resection of the prostate （TURP）. HER2 protein expression of TURP specimens was compared with that of the original biopsy specimens. Of these, 10 biopsy and 4 TURP specimens with HER2 IHC staining scores ≥ 2＋ were investigated for HER2 gene amplification status by fluorescent in situ hybridization （FISH）. Results： Of the 104 prostate biopsy specimens, HER2 protein expression was 0, 1＋, 2＋ and 3＋ in 49 （47.1%）, 45 （43.3%）, 8 （7.7%） and 2 （1.9%） cases, respectively. There was a significant association between HER2 expression and Gleason score （P = 0.026）. HER2 protein expression of prostate cancer tissues increased in 33.3% of patients after hormonal therapy. None of the 14 specimens with HER2 IHC scores 〉 2＋ showed HER2 gene amplification. Patients with HER2 scores 〉 2＋ had a significantly higher chance of dying from prostate cancer than those with HER2 scores of 0 （P = 0.004） and 1＋ （P = 0.034）. Multivariate Cox regression analysis showed that HER2 protein expression intensity was an independent predictor of cancer-related death （P = 0.039）. Conclusion： An HER2 IHC score 〉 2＋ should be defined as HER2 protein overexpression in prostate cancer. Overexpression of HER2 protein in cancer tissue might suggest an increased risk of dying from prostate cancer. HER2 protein expression increases in some individual patients after hormonal therapy.

Understanding the Past,Present,and Future of China's Economic Development——Based on A Unified Framework of Growth Theories

Through exploring the limitation of the neoclassical theory of economic growth,which classifies growth as a homogenous process,this paper reconciles various theories of economic development and explains the rises and falls of economic growth under a unified framework,focusing on incentives of the accumulation of physical and human capital.This paper classifies instances of economic growth into four categories—the Malthusian poverty trap,the Lewis dual model of economic development,the Lewis turning point,and Solow neoclassical growth model.This paper conducts empirical analysis of these categories of economic development as they are relevant to Chinese economic growth and discusses policy implications therein.

KIT and platelet-derived growth factor receptor α wild-type gastrointestinal stromal tumor associated with neurofibromatosis type 1: Two case reports

BACKGROUND Gastrointestinal stromal tumors(GISTs) associated with neurofibromatosis are uncommon compared to their gastrointestinal counterparts. Patients with neurofibromatosis type 1(NF-1) have an increased risk of developing gastrointestinal tumors, including rare types such as GIST.CASE SUMMARY A 60-year-old male Chinese patient was diagnosed with NF-1 10 years ago and presented with upper abdominal discomfort and black stools. Endoscopic ultrasonography and an enhanced abdominal computed tomography scan revealed a mass located 4 cm from the muscular layer of the descending duodenum. A 59-year-old Chinese woman who was diagnosed with NF-1 25 years ago presented with sudden unconsciousness and black stools. Multiple masses in the duodenum were noted by echogastroscopy and an enhanced abdominal computed tomography scan. Both patients presented with cutaneous neurofibromas. The histologic examination of tumors from both patients revealed spindle cells and low mitotic activity. Immunohistochemically, the tumor cells showed strong positivity for KIT(CD117), DOG-1, CD34, and Dehydrogenase Complex Subunit B, and negativity for SMA, desmin, S-100, and β-catenin. None of the six tumors from two patients had KIT exon 9, 11, 13, or 17 or platelet-derived growth factor receptor α exon 12 or 18 mutation, which is a typical finding for sporadic GISTs. None of the six tumors from the two patients had a BRAFV600 E mutation. The patients were alive and well during the follow-up period(range:0.6-5 yr).CONCLUSION There have been only a few previous reports of GISTs associated with NF-1.Although GISTs associated with NF-1 have morphologic and immunohistochemical similarities with GISTs, the pathogenesis, incidence,genetic background, and prognosis are not completely known. A medical history of NF-1 in a patient who has gastrointestinal bleeding or anemia and an intraabdominal mass with nonspecific computed tomography features may help in diagnosing GIST by virtue of the well-known association of these two entities.Molecular genetic studies of cases indicated that GISTs in NF-1 patients have a different pathogenesis than sporadic GISTs.

Inhibition of Ubiquitin-specific Protease 4 Attenuates Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells via Transforming Growth Factor Beta Receptor Type Ⅰ

Objective Ubiquitin-specific protease 4(USP4)facilitates the development of transforming growth factor-beta 1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)in various cancer cells.Moreover,EMT of renal tubular epithelial cells(RTECs)is required for the progression of renal interstitial fibrosis.However,the role of USP4 in EMT of RTECs remains unknown.The present study aimed to explore the effect of USP4 on the EMT of RTECs as well as the involved mechanism.Methods In established unilateral ureteral obstruction(UUO)rats and NRK-52E cells,immunohistochemistry and Western blot assays were performed.Results USP4 expression was increased significantly with obstruction time.In NRK-52E cells stimulated by TGF-β1,USP4 expression was increased in a time-dependent manner.In addition,USP4 silencing with specific siRNA indicated that USP4 protein was suppressed effectively.Meanwhile,USP4 siRNA treatment restored E-cadherin and weakened alpha smooth muscle actin(α-SMA)expression,indicating that USP4 may promote EMT.After treatment with USP4 siRNA and TGF-β1 for 24 h,the expression of TGF-β1 receptor type I(TβRI)was decreased.Conclusion USP4 promotes the EMT of RTECs through upregulating TβRI,thereby facilitating renal interstitial fibrosis.These findings may provide a potential target of USP4 in the treatment of renal fibrosis.

Current and emerging therapies in unresectable and recurrent gastric cancer

Gastric cancer is one of the most lethal cancers worldwide despite many advances and options in therapy. As it is often diagnosed at an advanced stage, prognosis is poor with a median overall survival of less than twelve months. Chemotherapy remains the mainstay of treatment for these patients but it confersonly a moderate survival advantage. There remains a need for new targeted treatment options and a way to better define patient populations who will benefit from these agents. In the past few years, there has been a better understanding of the biology, molecular profiling, and heterogeneity of gastric cancer. Our increased knowledge has led to the identification of gastric cancer subtypes and to the development of new targeted therapeutic agents. There are now two new targeted agents, trastuzumab and ramucirumab, that have recently been approved for the treatment of advanced and metastatic gastric cancer. There are also many other actively investigated targets, including epidermal growth factor receptor, the phosphatadylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway, c-Met, poly ADP-ribose polymerase, and immune checkpoint inhibition. In this review, we discuss the current management of advanced gastric cancer as well as emerging targeted therapies and immunotherapy.

Enhanced therapeutic effects for human pancreatic cancer by application K-ras and IGF-IR antisense oligodeoxynucleotides

AIM: To investigate the combined effects of K-ras antisense oligodeoxynucleotide (K-ras ASODN) specif ic to GTT point mutation at codon 12 and type Ⅰ insulin-like growth factor receptor (IGF-IR) antisense oligodeoxynucleotide (IGF-IR ASODN) on proliferation and apoptosis of human pancreatic cancer Patu8988 cells in vitro and in vivo. METHODS: K-ras gene point mutation and its style at codon 12 of human pancreatic cancer cell line Patu8988 were detected by using polymerase chain reaction with special sequence primers (PCR-SSP) and sequence analysis. According to the mutation style, K-ras mutation ASODN specifi c to K-ras point mutation at codon 12 was designed and composed. After K-ras ASODN and IGF-IR ASODN treated on Patu8988 cells respectively or cooperatively, the proliferation and morphological change of Patu8988 cells were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony forming assay andtransmission electron microscopy; the expression of K-ras and IGF-IR mRNA and protein in the treated cells was measured by reverse-transcript polymerase chain reaction (RT-PCR) and flow cytometry respectively; apoptosis was determined by flow cytometry. The combined antitumor activity of K-ras ASODN and IGF-IR ASODN was evaluated in BALB/c nude mice bearing human pancreatic cancer inoculated with Patu8988 cells. RESULTS: The results of PCR-SSP and sequence analysis showed that the human pancreatic cancer cell line Patu8988 had point mutation at codon 12, and the mutation style was GGT→GTT. 2-32 μg/mL K-ras ASODN and 2-32 μg/mL IGF-IR ASODN could inhibit Patu8988 cells' growth, induce apoptosis and decrease the expression of K-ras and IGF-IR mRNA and protein alone. However, there was much more effective inhibition of growth and induction of apoptosis by their combination than by each one alone. In tumor bearing mice, the combination of K-ras ASODN and IGF-IR ASODN showed a signif icant inhibitory effect on the growth of transplanted pancreatic cancer, resulting in a statistically signif icant difference compared with each alone. CONCLUSION: It has been found that K-ras ASODN combined with IGF-IR ASODN could cooperatively inhibit the growth of Patu8988 cells, and induce their apoptosis via reinforcing specific down regulation of K-ras and IGF-IR mRNA and protein expression.

Relationship between types of urban forest and PM_(2.5) capture at three growth stages of leaves

Particulate matter diameter ≤ 2.5 μm（PM2.5） causes direct harm to human health. Finding forms of urban forest systems that with the ability to reduce the amount of particulate matter in air effectively is the aim of this study. Five commonly cultivated kinds of urban forest types were studied in Beijing city at three stages of leaf growth. Results show that the urban forest system is capable of storing and capturing dust from the air. The types of shrubs and broadleaf trees that have the ability to capture PM2.5from the air are most effective when leaves have fully developed. In the leafless season, the conifer and mixed tree types are the most effective in removing dust from the air. For all kinds of forest types and stages of leaf growth, the PM2.5concentration is highest in the morning but lower in the afternoon and evening. Grassland cannot control particles suspended in the air,but can reduce dust pollution caused by dust from the ground blown by the wind back into the air.

Lapatinib-induced hepatitis: A case report

Lapatinib is an inhibitor of the tyrosine kinases of human epidermal growth factor receptor type 2 (HER2) and epidermal growth factor receptor type 1, with clinical activity in HER2-positive metastatic breast cancer. We present here a 60 year-old patient with metastatic breast cancer who presented with jaundice and increased serum aminotransferase levels and who had been treated with lapatinib for the previous 14 days. Laboratory tests excluded other causes of acute liver injury. Liver biopsy revealed lesions compatible with drug-induced hepatotoxicity. Bilirubin and liver enzymes returned to normal within three months of lapatinib discontinuation. Lapatinib should be included among the causes of druginduced hepatitis.

Anti-fibrotic effect of rosmarinic acid on inhibition of pterygium epithelial cells

AIM： To investigate the anti-fibrosis effect of rosmarinic acid（RA） in pterygium epithelial cells（PECs） to determine if RA is a potent agent for treating pterygium.METHODS： The PECs（1×10-4 cells/mL） were treated with 100 μmol/L of RA for 1, 3 and 6h. After RA treatment, the cell viability was determined by staining with acridine orange/DAPI and analysis via a NucleoC ounter NC-3000. The protein expression levels of type I collagen, transforming growth factor beta-1（TGF-β1）, TGF-β type Ⅱ receptor（TGF-βRⅡ）, p-Smad1/5, p-Smad2, p-Smad3, and Smad4 of the cell lysates were measured by Western blot analysis.RESULTS： The cell viability of PECs was significantly decreased after RA treatment（P〈0.01）. As the result, RA reduced the protein expression of typeⅠcollagen and TGF-β1 of PECs. Additionally, RA also inhibited TGF-β1/Smad signaling by decreasing the protein expressions of TGF-βRII, p-Smad1/5, p-Smad2, p-Smad3, and Smad4.CONCLUSION： This study demonstrate that RA could inhibit fibrosis of PECs by down-regulating type I collagen expression and TGF-β1/Smad signaling. Therefore, RA is a potent therapeutic agent for the treatment of pterygium.

Bamboo as a Genetic Resource and Its Utilization from the World Wide View Point

The latest effective utilization of bamboo resources is changing from domestic industry to mechanical industry. This fact will be required a lot of raw material from a large scale factory, therefore, what kind of bamboo should be selected for a material. So, this study discussed on this matter through investigation and experiment. Results of this study are as follows： 1） Characteristics of bamboo different from trees and grass; 2） Environmental factors： a） annual mean temperature in 10-15 ℃ shows good growth of culm in temperate area and more than 20 ℃ also shows in tropical area, b） Rainfall： more than 1,000 mm year-1 is necessary for growth of culm in temperate and tropical area, and still more in addition to two times of 100 mm month-1 in temperate area, and three times of 200 mm month-l in tropical area, c） Soil and topography： brown colored soil and flat or gentle slope show better growth in temperate area, but red colored soil and slope are not suitable in tropical area, d） Geographical distribution of bamboo related with growth type shown in Figs. 1-3. Productivity of bamboo： annual productivity of bamboo is the biggest compared with other type of vegetation; 4） Selection of two growth type of bamboo： many big bamboos are growing in tropical area; 5） Furthermore items discussed in this report.

EFFECTS OF TGF-β_1 ON THE EXPRESSION OF PLASMINOGEN ACTIVATOR INHIBITOR TYPE 1 IN CULTURED HUMAN RENAL INTERSTITIAL FIBROBLASTS

Objective To investigate the effects of transforming growth factor-β1 (TGF-β1 ) on the expression of plasminogen activator inhibitor type 1 (PAI-1 ) mRNA in renal interstitial fibrosis in vitro. Methods Human renal interstitial fibroblasts were isolated and cultured in vitro. The cells wers stimulated by TGF-β1 with different concentration (0 to 10ng/ml ) at different time (0 to 48h). The expression of PAI-1 mRNA was assayed by RT-PCR. Results TGF-β1, had dose-dependent and time-dependent effects on the expression of PAI-1 mRNA in renal interstitial fibroblasts. Conclusion TGF-β1 may partic- ipate in renal fibrosis with inducing the expression of PAI-1 mRNA in renal fibroblasts and affecting the synthesis and degradation of extracellular matrix (ECM).

Exploring complex urban growth and land use efficiency in China's developed regions:implications for territorial spatial planning

Developed regions in China have experienced rapid urban expansion and have consequently induced a series of challenging environmental issues since its economic reform and opening-up.Taking Zhejiang as a case study area,the present paper explores the complex types of urban growth over the last four decades as well as land use efficiency.Moreover,it discusses the implications of the aforementioned on China national territorial spatial planning(TSP).The acquired results have shown that:1)urban expansion has slowed down,exhibiting a three-stage trend of"slight increase(1980-1990)—dramatic growth(1990-2010)—slow growth(after 2010)";2)the complex types of urban growth reveal that the urban diffusion has been gradually controlled and the urban form tends to be more condensed;and 3)the mean values for pure technical efficiency(PTE)and scale efficiency(SE)of urban land use are 0.83 and 0.95 respectively,indicating PTE as the main factor restricting the improvement of urban land use.Based on these results,some beneficial policy implications and suggestions for TSP are provided.First,it is suggested that"Inventory Planning"will be the main direction of TSP other than"Incremental Planning".Secondly,we should pay more attention to the protection of cultivated land and ecological resources.Lastly,TSP should guide the economic growth away from simply relying on resource inputs and steer it toward technology and capital investment.

Effects of angiotensin Ⅱ receptor antagonist on expression of collagen Ⅲ,collagen Ⅴ,and transforming growth factor β_1 in the airway walls of sensitized rats

Background Repeated attacks of bronchial asthma lead to different degrees of airway remodeling,the mechanism of which is not yet clear. Some evidences indicate that it is related to the excessive expression of some growth promotion factors. Angiotensin Ⅱ is a polypeptide that may be involved in airway remodeling. To evaluate its role in airway remodeling in asthma,we observed the effects of an angiotensin Ⅱ type 1 receptor antagonist (valsartan) on the expression of collagen Ⅲ,collagen Ⅴ,and transforming growth factor β_1 (TGF-β_1) mRNA and protein in the airway walls of sensitized rats.Methods Forty Wistar rats were randomly divided into 5 groups: control group,sensitized group,and valsartan groups 1,2,and 3. The rats in the sensitized group and in valsartan groups 1,2,and 3 were sensitized and challenged with ovalbumin. Rats in control group were sensitized and challenged with 0.9% NaCl. Rats from valsartan groups 1,2,and 3 were drenched with valsartan (10 μg, 20 μg,or 30 μg,respectively) at the time of the ovalbumin challenges. The expression of collagen Ⅲ,collagen Ⅴ,and TGF-β_1 protein were detected using immunohistochemical method in combination with image analysis methods. The expression of TGF-β_1 mRNA was detected by in situ hybridization. Results The expression in the airways of collagen Ⅲ and collagen Ⅴ was significantly higher in rats from the sensitized group (7.73±0.81, 1.34±0.28) and from valsartan groups 1,2,and 3 (5.73±0.64, 1.13±0.15; 4.96±0.51, 0.98±0.08; 4.43±0.35, 0.93±0.06,respectively) than those in the control group (2.65±0.38, 0.67±0.08,P <0.05). In addition,collagen levels were significantly lower in valsartan groups 1,2,and 3 than those from the sensitized group ( P <0.05). The expression of TGF-β_1 mRNA and protein in the airways was significantly higher in rats from the sensitized group (20.49%±3.46%,29.73%±3.25%) and from valsartan groups 1,2,and 3 (16.47%±1.94%, 19.41%±1.87%; 14.38%±1.58%, 18.29%±1.43%; 12.96%±1.73%, 18.63%±1.11%,respectively) than that from the control group (7.84%±1.61%, 5.63%±1.07%,P <0.05). TGF-β_1 mRNA and protein levels were significantly lower in valsartan groups 1,2,and 3 than that in the sensitized group ( P <0.05). Conclusions Angiotensin Ⅱ receptor antagonist valsartan can suppress synthesis of collagen Ⅲ and collagen Ⅴ by downregulating TGF-β_1 mRNA and protein expression. Valsartan can decrease airway remodeling and could play a role in asthma therapy.

Angiotensin Ⅱ type 1 receptor antagonist inhibits growth of human bladder cancer xenograft

AngiotensinⅡis known as a key biologically active peptide in rennin-angiotensin system, which regulates blood pressure, and angiotensinⅡtype 1 receptor (AT1R) antagonists are widely used as antihypertensive drugs. Since several human cancers have been reported to express AT1R, it is worthwhile to test whether AT1R antagonists

Cancer stem cells and HER2 positive breast cancer:The story so far

Human Epidermal Growth Factor Receptor type 2(HER2)gene amplification and/or protein overexpression is observed in patients suffering from HER2t breast cancer.This subtype of breast cancer has improved prognosis due to availability of anti-HER2 therapy.However,drug resistance and tumor recurrence still remains a major concern.Cancer Stem Cells(CSCs)are believed to constitute the subset of cell population that is resistant to drug treatment and possesses characteristics of stem cells.CSCs enable the tumors to thrive despite major insults.This review provides a comprehensive idea about the concept of CSCs in context of HER2t breast cancer by providing the description of the markers that are used for the identification of CSCs and by elucidating the signaling pathways that are associated with HER2t breast CSCs.Furthermore,the review also describes the interaction of HER2 with those signaling pathways and the future of targeting CSCs in HER2t breast cancer.

A comparative study of spatiotemporal patterns of urban expansion in six major cities of the Yangtze River Delta from 1980 to 2015

Introduction:China has been experiencing dramatic urbanization in parallel with its eco-nomic boom over the past three to four decades.The Yangtze River Delta(YRD),as the most important engine in the Chinese economy,has pioneered in the rapid urbanization road of China since the late 19705.We quantifed and compared the spatiotemporal patterns of urban expansion in six major cities in the YRD urban agglomeration between 1980 and 2015.Outcomes:We found that Sha nghai,Nanjing,Hangzhou,Wuxi,Suzhou and Ningbo expanded by an annual rate of 5.4%,5.9%,9.6%,7.4%,6.3%and 8.1%from 1980 to 2015,suggesting larger cities generally possess lower growth rates.Spatiotemporal patterns of urban expansion are defined by multiple forces including physical conditions and urban planning and policy.The urbanization processes in Shanghai,Nanjing and Hangzhou gen-erally conformed with the difusion-coales cence theory as the number of patches(NP)and patch density(PD)of urbanized land peaked and the proportion of leapfrogging urban growth type began to decrease around 2005,which separating their urbanization processes into difusion phase before and coalescence phase after.In contrast,Suzhou,Wuxi and Ningbo is either in the diffusion or in the transition phase from diffusion to coalescence,not showing temporal dynamics of diffusion-coalescence phase across the study period,which might be related to the fact that the urban areas in these three cities were more dispersive in space than that of other cities.Conclusions:These spatially explicit findings are the fundamental cornerstone to understand the characteristics,drivers and consequences of urban expansion in the urban agglomera-tions,and then detect the feasibility of general urbanization theories and further advance in-depth theoretical understanding to support a sustainable urban future.

Biological parameters and feeding behaviour of invasive whelk Rapana venosa Valenciennes,1846 in the south-eastern Black Sea of Turkey

Objective:To determine length-weight relationships,growth type and feeding behavior of the benthic predator Rapa whelk at the coast of Camburnu,south-eastern Black Sea.Methods:Rapa whelk was monthly collected by dredge sampling on the south-eastern Black Sea at 20 m depth.The relationships between morphometric parameters of Rapa whelk were described by linear and exponential models.The allometric growth of each variable relative to shell length(SL)was calculated from the function Y=aSL^(b) or logY=loga_(+)blogSL.The functional regression b values were tested by t-test at the 0.05 significance level if it was significantly different from isometric growth.The total time spent on feeding either on mussel tissue or live mussels was recorded for each individual under controlled conditions in laboratory.Results:The length-weight relationships showed positive allometric growth and no inter-sex variability.Body size in the male population was significantly higher than in the individuals of the female.All characters in males and females showed a trend towards allometry rather than isometry.While the total time spent feeding increased with increasing prey size the total time that Rapana venosa spent feeding decreased with increasing Rapa whelk size.The total average feeding time needed by Rapa whelks was 160 min.But they took 310 min on live mussels in 27-28℃ in the laboratory conditions.Conclusions:Length and weight relationships,growth type,total time spent feeding of this species were explained in details for this region.It would be useful to sustainable management in the south-eastern Black Sea of Turkey.The results about the feeding behaviour of this species will contribute to the understanding of the role of this species within the ecosystem.

The World Economy is Deeply Affected by the Negative Impact Of Di-Globalization

In the year 2019, all the main economies in the world are relaxing monetary policy. The sluggish growth of the world economy presents a general slowdown in the growth of all types of economies. The International Monetary Fund predicts that the global economic growth rate will be about 3% in 2019, 0.6% lower than that in 2018, the lowest level since the international financial crisis in 2008.