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Proteomic study was used to clarify the mechanism of hepatocellular carcinoma (HCC) immune escape concerning Dendritic cells (DCs’) dysfunction and their association with HCC invasion. Human peripheral blood mononuclear cells (PBMCs) derived DCs from healthy donors were pulsed with soluble cell lysates prepared from different metastatic potential human HCC cell lines. The total protein of these DCs was analyzed by two-dimensional electrophoresis and Electro-Spray Mass Spectrometry. The allostimulatoy capacity and phenotype of these DCs were also evaluated. The clinical significance of β-centractin, one of the largest quantitative changed spot, down-regulation in DCs was further evaluated in autologous PBMCs derived DCs pulsed with auto-tumor lysates in 26 HCC patients. The expression of β-centractin was found to be considerably lower either in DCs pulsed with HCCLM6 (high metastatic potential HCC cell line) lysates, accompanied by down-regulation of CD86 molecule and impaired allostimulatory capacity, than those of DCs pulsed with lysates from HCC cell lines with low or without metastatic potential or in DCs pulsed with lysates from HCC with invasiveness than those without invasiveness. The down-regulation of β-centractin in DCs pulsed with high metastatic potential HCC lysates might associate with DCs dysfunction and HCC invasiveness. [ABSTRACT FROM AUTHOR]

Focal nodular hyperplasia (FNH) is a rare benign hepatic lesion, which is usually asymptomatic and solitary. Complications such as rupture and bleeding are extremely rare and only five cases have existed since 1975. We report a case of a 26-year-old woman with spontaneous rupture and hemorrhage of huge FNH presenting as acute abdomen. Different to previously recorded cases, this case was concomitant with multiple hepatic adenomas, which was misdiagnosed as rupture of hepatocellular carcinoma (HCC) with multiple intrahepatic spreading in another hospital. Our case highlights thepossible association between the size of FNH and the risk of rupture, and emphasizes the need to consider this in making treatment decisions. Although a conservative approach for asymptomatic FNH is well established, the potential for surgical intervention should always be considered, especially for large FNH. We recommend surgical resection of large FNH (>5 cm), symptomatic or not, rather than observation. [ABSTRACT FROM AUTHOR]

Background/Aims: To study the impact of hepatitis B e antigen on tumor recurrence and patients’ survival after curative resection of hepatocellular carcinoma. Methods: Two hundred and three patients with small hepatocellular carcinomas (⩽3cm) who had undergone curative resection were divided into HBeAg-positive group and HBeAg-negative group. Clinicopathological factors and postoperative outcomes were compared between groups, and risk factors for survival and recurrence were studied. Results: The median follow-up time was 32.9months. Patients with negative HBeAg had higher 5-year overall survival rates (76% vs 53.9%, hazards ratio (HR): 2.363, 95% CI: 1.335–4.181, p =0.002) and 5-year disease-free survival rates (52.9% vs 37.4%, HR: 1.603, 95% CI: 1.00–2.561, p =0.046).There was no significant difference in operative morbidity and tumor factors between the two groups, but younger age, higher serum alanine aminotransferase levels, and more macronodular cirrhosis were found in the HBeAg-positive group. Multivariate analysis revealed that age >50years, HBeAg positivity and macronodular cirrhosis were independent factors for overall survival, and HBeAg positivity and multiple tumor nodules were independent factors for disease-free survival. Positive serum HBeAg was associated with a higher risk of early recurrence (within 1year). Conclusions: HBeAg is associated with a higher risk of early recurrence and poorer survival in patients after curative resection of small HCC. [Copyright &y& Elsevier]

This paper reports that the nonlinear refractive index of a novel organic optical storage film doped azo-diphenylamine polymer is measured by using the Z-scan technique. The nonlinear refractive index up to 3.7 × 10[?]6 cm2/W induced by thermo-optical effect is obtained. It indicates that the sample has excellent optical nonlinear properties. The physical mechanism of the great nonlinear optical effect is analysed and the optical conjugate characteristic is also discussed with degenerate four-wave-mixing. The phase conjugate wave diffracted from the formative refractive index grating in the sample is acquired and its equivalent reflectivity reaches about 22%. On this basis, the reflective wave phase-conjugated mirror system was designed, and the image aberration experienced in propagation in the storage experiment is corrected by using the system. [ABSTRACT FROM AUTHOR]

We perform a comparative study on the electroluminescence (EL) and photoluminescence (PL) of Si nanocrystal-doped SiO2 (nc-Si:SiO2) and SiO2, and clarify whether the contribution from Si nanocrystals in the EL of nc-Si:SiO2 truly exists. The results unambiguously indicate the presence of EL of Si nanocrystals. The difference of peak positions between the EL and PL spectra are discussed. It is found that the normal method of passivation to enhance the PL of Si nanocrystals is not equally effective for the EL, hence new methods need to be explored to promote the EL of Si nanocrystals. [ABSTRACT FROM AUTHOR]

Abstract: The evolution of Si nanostructures induced by Ar+ ion sputtering on Si(100) was studied with electrostatic force microscopy (EFM) as a function of post-annealing temperature (T =room temperature–800°C) and time (t =0–160min). The post-annealing of the nanostructure was conducted in vacuum. It was found that with T increasing, the EFM contrast degraded steadily and became nearly undetectable at T =800°C; with t increasing at T =800°C, the EFM contrast fell down steadily as well. However, the surface morphology and roughness were much less affected after annealing. The results suggest that the as-formed Si nanostructures may not be epitaxially grown on Si(100) substrate as claimed before. A plane capacitance model supported this conclusion. [Copyright &y& Elsevier]

Abstract: We report the evolution of photoluminescence (PL) of Si nanocrystals (nc-Si) embedded in a matrix of SiO2 during Ar+ ion bombardment. The integrated intensity of nc-Si PL falls down drastically before the Ar+ ion fluence of 1015 ionscm−2, and then decreases slowly with the increasing ion fluence. At the meantime, the PL peak position blueshifts steadily before the fluence of 1015 ionscm−2, and then changes in an oscillatory manner. Also it is found that the nc-Si PL of the Ar+-irradiated sample can be partly recovered after annealing at 800°C in nitrogen, but can be almost totally recovered after annealing in oxygen. The results confirm that the ion irradiation-induced defects are made up of oxygen vacancies, which absorb light strongly. The oscillatory peak shift of nc-Si can be related to a size-distance distribution of nc-Si in SiO2. [Copyright &y& Elsevier]

By using an Ar+ion laser, a tunable Rh 6 G dye laser (linewidth 0.5 cm?1) pumped by the second harmonic of a YAG:Nd laser and a Coherent 899-21 dye laser as light sources and using a monochromator, a phase-locking amplifier and a computer as the data detecting system, we detect the optical properties of Eu3+-doped Y2SiO5crystal. Persistent spectral hole burning (PSHB) are observed in the Eu3+ions spectral lines (5D0?7F0transition) in the crystal at the temperature of 16 K. For 15 mW dye laser burning the crystal for 0.1 s spectral holes with hole width about 80 MHz both at 579.62 nm and at 579.82 nm are detected and the holes can remain for a long time, more than 10 h. [ABSTRACT FROM AUTHOR]

Abstract: Using a phage display approach, we identified AWYPLPP peptide as a specific peptide ligand that binds to the cell surface of highly metastatic human hepatocellular carcinoma (HCC). Moreover, the peptide was able to promote in vitro invasion of highly metastatic HCC cells by activating matrix metalloproteinase-9 and in vivo lung metastasis of HCC tumors. These results indicate that AWYPLPP peptide likely recognizes a novel receptor that is selectively expressed on the cell surface of highly metastatic HCC and mediates cellular activities associated with the invasive phenotype. Identification of the receptor for the AWYPLPP peptide may provide new insights into the molecular mechanism of HCC metastasis. [Copyright &y& Elsevier]

Abstract: The ion flux dependence of the self-organized Si nanodots induced by 1.5keV Ar+ ion sputter erosion has been studied. It shows that for the regime with ion flux >∼280μA/cm2, the currently adopted Bradley–Harper (BH) model, which is incorporated in a dynamic continuum equation holds valid. However, for ion flux <∼280μA/cm2, the measured dot size and surface roughness deviate drastically from the BH model. To interpret the data for this lower ion flux regime, the effect of the Ehrlich–Schwoebel (ES) step-edge barrier was introduced into the continuum equation. A consistency between the calculated and the experimental results was reached, furthermore, a reasonable trend was found, that is, the effective ES diffusion decreases steadily with the increasing ion flux, and at ∼280μA/cm2, it became negligibly small. [Copyright &y& Elsevier]

We aimed to evaluate the prognostic value of preoperative plasma osteopontin (OPN) levels in 101 patients with hepatocellular carcinoma (HCC) who underwent liver resection. Plasma OPN levels were detected by ELISA. The association of plasma OPN levels of patients with clinicopathological characteristics, tumor recurrence, and survival was analyzed. The median plasma OPN level of patients was 176.90 ng/ml (range 13.73–780.00 ng/ml), which was significantly higher than that of 24 healthy volunteers (63.74 ng/ml, range 12.20–122.32 ng/ml). Plasma OPN levels were significantly different in patients with different numbers of tumor nodules (168.18 and 217.11 ng/ml for single and multiple nodules, respectively; P = 0.002), different Edmondson’s grades (201.24, 168.36, and 503.58 ng/ml for grades I, II, and III/IV, respectively; P = 0.015), and different TNM stages (168.16, 167.54, and 216.18 ng/ml for stages I, II, and III/IV, respectively; P = 0.016). Significantly higher plasma OPN levels were found in patients with a recurrence of HCC after resection, compared with those without recurrence (213.55 versus 153.70 ng/ml; P = 0.0013). A higher plasma OPN level was a leading independent prognostic factor for both overall survival (OS) and disease-free survival (DFS) in univariate and multivariate Cox models. This suggests that the preoperative plasma OPN level can be used as a predictive marker for HCC recurrence and may be helpful to assess the prognosis of patients with HCC after surgery. [ABSTRACT FROM AUTHOR]

Abstract: We observed a synergetic effect between ion energy and sample temperature in the formation of distinct dot pattern on Si(110) by Ar+ ion sputtering. The ion flux was 20μA/cm2, a value smaller than those used in preceding reports by one or two orders of magnitude. In experiments, the ion energy was from 1 to 5keV, and the temperature from room temperature to 800°C. A phase diagram indicating the ranges of ion energy and temperature within which distinct dot patterns can be achieved has been obtained. Data analyses and simulation results reveal that the synergetic effect is consistent with the effect of the Ehrlich–Schwoebel step-edge barrier, rather than the Bradley–Harper model. [Copyright &y& Elsevier]

Summary: Hepatocellular carcinoma (HCC) is an aggressive malignancy mainly due to metastases or postsurgical recurrence. We postulate that metastases are influenced by the liver microenvironment. Here, we show that a unique inflammation/immune response-related signature is associated with noncancerous hepatic tissues from metastatic HCC patients. This signature is principally different from that of the tumor. A global Th1/Th2-like cytokine shift in the venous metastasis-associated liver microenvironment coincides with elevated expression of macrophage colony-stimulating factor (CSF1). Moreover, a refined 17 gene signature was validated as a superior predictor of HCC venous metastases in an independent cohort, when compared to other clinical prognostic parameters. We suggest that a predominant humoral cytokine profile occurs in the metastatic liver milieu and that a shift toward anti-inflammatory/immune-suppressive responses may promote HCC metastases. [Copyright &y& Elsevier]

Purpose: We demonstrated that chromosome 8p deletion is associated with metastasis of human hepatocellular carcinoma (HCC). This study assesses the value of circulating plasma DNA level and its allelic imbalance (AI) on chromosome 8p in the prediction of HCC prognosis. Methods: Blood samples were collected from 79 patients with HCC before operation, 20 patients with liver cirrhosis, and 20 healthy volunteers. The HCC and adjacent non-tumor liver tissues were obtained from surgical specimens. Plasma DNA was extracted and quantified. Two microsatellite markers on chromosome 8p, D8S258 and D8S264, were selected and used in the AI analysis. Results: The circulating plasma DNA level was found to closely associate with tumor size ( P=0.008) and TNM stage ( P=0.040), negatively associate with the 3-year disease-free survival (DFS) ( P=0.017) and overall survival (OS) ( P=0.001). AI at D8S258 in plasma DNA was significantly correlated with tumor differentiation ( P=0.050), TNM stage ( P=0.010), and vascular invasion ( P=0.023), negatively correlated with the 3-year DFS ( P=0.005) and OS ( P=0.036). However, AI at D8S264 was only closely associated with 3-year DFS ( P=0.014). Combined detection of AI at D8S258 and circulating plasma DNA level was independently associated with DFS ( P=0.018) and OS ( P=0.002) of patients with HCC. For patients with both AI at D8S258 and a higher level of plasma DNA, the 3-year DFS and 3-year OS rates were decreased remarkably ( P=0.014 and 0.044). Conclusion: Combination of circulating plasma DNA level and AI at D8S258 might be an independent predictor for prognosis of HCC patients. [ABSTRACT FROM AUTHOR]

Aim: To elucidate the relationship between local immunocompetent cells and prognosis of human hepatocellular carcinoma (HCC) after resection. Methods: HE staining and immunohistochemical study were carried out on specimens from patients underwent surgical resection. Local immunocompetent cells, such as dendritic cells (DCs), memory T cells, CD3+ T lymphocytes and CD8+ T lymphocytes, were counted and their relationships with tumor-free survival rate were analyzed by grouping DCs with the T lymphocytes retrospectively. Results: The number grade of infiltrating immunocompetent cells in HCC nodules and pericancerous tissues under HE staining had no significant correlation with tumor-free survival time ( P=0.054, 0.071, respectively). DCs were mainly among tumor cells, encircling tumor cells with their pseudopodia and were in contact with T lymphocytes. A certain number of DCs in HCC nodules (≥25/10HPF) statistically correlated to tumor-free survival time ( P=0.005), while a certain number of DCs in pericancerous tissues (≥28/10HPF) had no correlation with tumor-free survival time ( P=0.329). The number of memory T cells, CD3+ T lymphocytes and CD8+ T lymphocytes in HCC nodules strongly correlated to tumor-free survival time ( P=0.003, 0.005, 0.037, respectively). The tumor-free survival rate curves revealed that the more DCs or together with memory T cells/CD3+ T lymphocytes or that the more CD8+ T lymphocytes were detected in HCC nodules, the better the prognosis would be. Conclusions: Marked infiltration of DCs in HCC nodules was closely related to the prognosis of HCC after surgical resection and can be served as a predictive index for recurrence and metastasis of HCC. [ABSTRACT FROM AUTHOR]

Purpose: A comparative proteomic approach was used to identify and analyze proteins related to metastasis of hepatocellular carcinoma (HCC). Methods: Proteins extracted from 12 HCC tissue specimens (six with metastases and six without) were separated by two-dimensional gel electrophoresis (2-DE). The protein spots exhibiting statistical alternations between the two groups through computerized image analysis were then identified by mass spectrometry. In addition immunohistochemistry (IHC), Western blotting and RT-PCR were performed to verify the expression of certain candidate proteins. Results: 16 proteins including HSP27, S100A11, CK18 were annotated by mass spectrometry, relevant to chaperone function, cell mobility, cytoskeletal architecture, respectively. Most were previously unconnected with metastasis of HCC. Of these HSP27 was found overexpressed consistently in 2-DE patterns of all metastatic HCC tissues compared with nonmetastatic ones. IHC and Western blotting of HCC tissues confirmed this difference while RT-PCR did not. Conclusion: There are various proteins joined together in HCC metastasis. The overexpression of HSP27 may serve as a biomarker for early detection and therapeutic targets unique to the metastatic phenotype of HCC. [ABSTRACT FROM AUTHOR]

A prophylactic abdominal drainage catheter is routinely inserted by many surgeons in patients after hepatic resection. Between January 2002 and September 2004, 462 consecutive patients who had undergone hepatic resection using a clamp crushing method by the same surgical team were retrospectively divided into the drainage group (n = 357) and the nondrainage group (n = 105). There was no difference in hospital mortality between the two groups of patients (drainage group, 0.6% vs. nondrainage group, 0%; P = 1.0). However, there was a greater incidence of surgical complications in the drainage group (31.4% vs. 8.6%, P < 0.001), and greater incidence of wound complications and subphrenic complications in the drainage group compared to the nondrainage group (24.4% vs. 4.8%, P < 0.001). In addition, the mean (± SEM) postoperative hospital stay of the drainage group was 13 ± 6.5 days, which was significantly longer than that of the nondrainage group (9.7 ± 3.3 days, P = 0.001). On multivariate analysis, abdominal drainage and intraoperative bleeding were the independent risk factors that were significantly associated with the incidence of drainage-related complications. The results suggested that routine abdominal drainage is unnecessary after hepatic resection when the conventional clamp crushing method is used during parenchyma transection. [Copyright &y& Elsevier]

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

Abstract: The HCCLM3 cell line was established at the authors'' institute from the lung metastatic lesions of BALB/c nude mice bearing human hepatocellular carcinoma (HCC) from the metastatic HCC cell line MHCC97-H. It has been shown to have a high potential for lung metastases and extensive metastases when the cells are inoculated subcutaneously or orthotopically in athymic nude mice. In the present study, the molecular cytogenetic characteristics of this cell line were evaluated with conventional G-banding, comparative genomic hybridization, and multiplex fluorescence in situ hybridization. A hyperdiploid karyotype of 53–58 chromosomes with 10 marker chromosomes was identified. The chromosomal aberrations such as i(X)(q10), der(Y)t(Y;18)(q12;p11), der(3)t(3;20) (p25;q13), der(4)t(4;8)(q31;q22)5, der(9)t(9;13)(p21;q22), der(14)t(14;22)(p13;q13), and der(15) t(15;21)(q11;q22) were described for the first time in human HCC cells. The analysis of this cell line through a combination of molecular cytogenetic techniques provides information on the possible molecular mechanisms involved in the metastatic process of HCC. [Copyright &y& Elsevier]

An earlier report demonstrated that interferon alpha (IFN-a) inhibited tumor growth and recurrence in an MHCC97 xenograft model in nude mice by suppressing tumor angiogenesis rather than by inhibiting tumor cell proliferation. However, the underlying molecular mechanism was not fully elucidated. In this study, we demonstrated that IFN-a 2a could downregulate VEGF expression both in mRNA and in protein levels, as well as downregulating HIF-1a mRNA expression in MHCC97 cells in vitro. A cDNA micro array analysis followed by Northern and Western blot analysis revealed that PI3 kinase and MAP kinase signaling pathways might be inhibited by IFN-a 2a. Blocking the function of IFN-a receptor with a specific peptide could eliminate the inhibitory effects of IFN-a 2a on VEGF expression. In addition, wortmannin and PD098059, respective inhibitors of the PI3 kinase and the MAP kinase signaling pathways, when used independently or in combination, could also downregulate the VEGF synthesis and secretion in a similar pattern of IFN-a 2a. These observations may lead to the conclusion that IFN-a 2a could suppress VEGF synthesis and secretion by downregulating HIF-1a expression, via inhibition of the PI3 kinase and/or the MAP kinase signaling pathways. [ABSTRACT FROM AUTHOR]

Purpose: Cell-matrix adhesive interaction has an important role in the invasive process of tumor cells, and integrins are the major receptors mediating cell-matrix adhesion. The current study is to investigate the modulation of basement membrane (BM) proteins, especially collagen IV (C IV), laminin (LN), and fibronectin (FN) in the invasive processes of human hepatocellular carcinoma (HCC) cells in vitro, and to reveal the roles of β1 integrins and RGD-containing oligopeptide in the cell-matrix interaction. Methods: Static adhesion assay was performed to study the rates of adhesion of MHCC97-H cells, treated or untreated with anti-β1 (2 μg ml-1) and GRGDS, to C IV (50 μg ml-1), LN (50 μg ml-1) or FN (50 μg ml-1). Gelatin zymography was used to detect the secretion of MMPs in the conditioned medium of MHCC97-H cells incubated 24 h by C IV, LN or FN, and interactions with anti-β1 and GRGDS. Transwell chamber assay was used to investigate the influence of C IV, LN or FN, interacting with anti-β1 and GRGDS, on the cellular mobility of MHCC97-H cells. Results: Compared with blank control group, MHCC97-H cells showed significantly higher rates of adhesion to C IV, LN, and FN. Pretreatment with anti-β1 could suppress adhesion to C IV, LN or FN, but GRGDS inhibited adhesion to FN (P<0.05) only. LN and FN could stimulate the secretion of MMPs by MHCC97-H cells cultured in vitro, especially MMP-9 and its activated type. Treatment with anti-β1 could partly counteract the effects of LN and FN. GRGDS could prominently induce the secretion of MMPs, but the effect could be inhibited by pretreatment of anti-β1. The results of Transwell chamber assay showed that LN, FN, and GRGDS could increase the number of tumor cells penetrating the microporous membrane, but the data of C IV did not reach significance. The effects were partly counteracted by anti-β1. Conclusion: BM proteins play an active role in the invasive process of human hepatocellular carcinoma cells. Integrin β1 is an important molecule which mediates the cell-matrix adhesive interaction of tumor cells. RGD-containing peptides competitively combine with the binding site of integrin β1, and the effects of FN are RGD sequence-dependent. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the function of the KIAA0008 gene, one of the leading genes in the signature associated with hepatocellular carcinoma (HCC) metastasis selected by cDNA microarray, and especially its possible roles in invasion and metastasis of hepato-cellular carcinoma. Methods: Expression levels of KIAA0008 in 27 primary tumors and 23 matched non-tumor liver tissues from HCC patients, and four HCC cell lines with different metastatic potentials were detected by semi-quantitative RT-PCR and real-time RT-PCR. Recombinant expression plasmid vectors of the KIAA0008 gene were constructed and transfected into I-ICC cells. The subcellular localization of the KIAA0008 gene product and in vitro effects of KIAA0008 overexpression on proliferation and invasion of HCC cell line were also investigated. Results: Expression levels of KIAA0008 in HCC tissues were statistically higher than those of paired non-tumorous liver tissues (P < 0.001, paired Wilcoxon test), and in HCCs with high invasiveness these were statistically higher than those with low invasiveness (P= 0.002, Mann-Whitney test). In the four HCC cell lines with an identical genetic background and stepwise higher invasiveness potentials, its expression was consistent with their invasiveness potential. The KIAA0008 gene product was concentrated on the nucleus and cell membrane of HCC cells, without any distribution in the cytoplasm. Overexpression of KIAA0008 in the MHCC97L cell line resulted in increased cell proliferation, colony formation, and invasion. Conclusions: KIAA0008 expression is associated with invasiveness of HCC; overexpression of KIAA0008 leads to a more invasive phenotype of HCC cell lines. [ABSTRACT FROM AUTHOR]

Objectives: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in China and, due to the limited efficacy of currently available therapies, is responsible for a large number of deaths. IFN-α therapy has shown promise in the treatment of various forms of human cancer and is considered in the treatment of HCC. Previous results from our group showed that high doses of IFN-α exert a significant antiproliferative effect on MHCC97 human xenografts in nude mice, but not on MHCC97 cells when tested in vitro. Here we present experiments designed to characterize the molecular mechanism underlying the defective response of MHCC97 cells to IFN-α. Elucidation of the mechanism underlying the defective response of MHCC97 to IFN-α may help to explain and possibly to overcome clinical failures of this form of tumor therapy. Methods: IFN-α2a was administered between 3,000 and 10,000 IU/ml, a range strongly inhibiting proliferation in other cell lines. Gene expression profiles of MHCC97 cells were obtained before and after treatment with IFN-α2a using cDNA microarray analysis. The transcriptional activity of relevant genes responding to IFN-α2a in the cDNA microarray experiments was confirmed by RT-PCR and Northern blot analysis. Transient transfection with an expression vector was used to restore p48-ISGFγ (IRF9) protein levels. Cell proliferation was evaluated using the MTT assay. Results: Although IFN-α treatment caused the activation of several signal transduction pathways in MHCC97 cells, the lack of an antiproliferative effect was found to mainly derive from a defect in the activation of the transcription factor ISGF3 required for Jak/STATS signaling. We show that the defect in ISGF3 activation is mainly caused by the absence of one of its essential components, the protein p48-ISGFγ from MHCC97 cells. Indeed, transient expression of p48-ISGFγ restores sensitivity to IFN-α2a. Although the mRNA levels of p48-ISGFγ were normal in MHCC97 cells, mutations could be detected in the gene coding for the protein. We hypothesize, therefore, that these mutations alter the message or protein stability, leading to the reduced protein levels observed. Conclusion: Our results confirm the important role of Jak/STATS signaling in the antiproliferative effects of IFN-α in tumor cells and indicate that defects in ISGF3 can cause resistance to IFN-α2a treatment. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: The comparative study of differentially expression of protein profiles of hepatocellular carcinoma cell lines with various metastasic potential and screening key molecules related to hepatocellular carcinoma metastasis and recurrence. Methods: Using two-dimensional electrophoresis and liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS), we analyzed differentially displayed proteomics of human hepatocellular carcinoma cell lines Hep3B, MHCC97L, MHCC97H with different metastasic potential. Results: Approximate 1,000 protein spots were detected on silver-stained gel by ImageMaster (977± 113 spots in Hep3B, 1092±40 in MHCC97L, and 889± 14 in MHCC97H). Fifty distinct different protein spots were analyzed with online LC- ESI-MS/MS. Only 26 protein spots had a positive result, including annexin1, S100A4, and so on. In comparison with nonmetastasis Hep3B cell lines, there were 16 proteins overexpressed in MHCC97H and MHCC97L, 10 proteins underexpressed in MHCC97H and MHCC97L. Applying cell immunohistochemistry and RT-PCR, we further validated two interesting and dif- ferent proteins, annexinl and S100A4. Conclusion: The protein profile of metastatic hepatocellular carcinoma cell lines displayed obvious differences compared with non-metastatic liver cancer cell lines. The results imply that various different proteins may lead to HCC metastasis together. [ABSTRACT FROM AUTHOR]

Purpose. To establish a “stepwise metastatic human hepatocellular carcinoma (HCC) cell model system” for in-depth study of the underlying mechanisms of HCC metastasis. Methods. Using MHCC97— a metastatic human hepatocellular carcinoma (HCC) cell line reported in 1999—as the parent cells, we subsequently established three cell lines (MHCC97-L, HMCC97-H, and HCCLM3) with increasing spontaneous metastatic potential. Now, the fourth cell line with unique multiple metastatic characteristics has been established by six rounds of in vivo selection. Results. This cell line, designated as HCCLM6, is a polygonal epithelial cell with hypotriploid karyotype, the modal chromosomes are 55-58, and marker chromosomal abnormalities include i(1) (q10), i(8)(q10), der (4) t(4;8)(q31;q22), i(X)(q10). The cell population doubling time was 32 h. Fluorescent PCR showed HBV DNA integration in the cellular genome. Thirty-five days after HCCLM6 was injected subcutaneously into BALB/c nude mice, prominent lung metastases occurred in 100% of the recipient animals. When tumor tissue was orthotopically implanted into the liver of nude mouse, widespread loco-regional and pulmonary metastases occurred. Inoculation of this cell into the footpad of nude mice also produced 75% regional lymph node metastasis. Compared with MHCC97-L which was not metastastatic via subcutaneous or footpad inoculation and 40% metastatic via orthotopic inoculation, HCCLM6 had increased expression of matrix metalloproteinase (MMP-2 and MMP-9) and cytokeratin 19 (CK19), and decreased expression of Rb2/p130. The establishment of this new cell line has completed our stepwise metastatic HCC cell mode system, which was characterized by a similar genetic background but with significant differences in spontaneous metastasis behavior. Conclusions. The study supports the theory that cancer metastasis is a highly selective dynamic process and the cell model system could be a useful platform for the study of HCC metastasis. [ABSTRACT FROM AUTHOR]

Purpose. To establish stable green fluorescent protein (GFP)-expressing metastatic human hepatocellular carcinoma (HCC) cell lines with different metastatic potential for long-term in vivo studies of metastasis and angiogenesis. Methods. The pIRES2-EGFP vector, which contains an enhanced GFP gene, was transfected into MHCC97-H and MHCC97-L, HCC cell lines with different metastatic potential. The stability of GFP expression, basic biological characteristics, invasion abilities in vitro, and spontaneous metastasis in vivo of the new cell lines (MHCC97-HG and MHCC97-LG) were studied. Microvessel density (MVD) of orthotopic implanted tumors was compared by anti-CD31 immunohistochemical staining, and real-time angiogenesis and metastasis of GFP-transfected tumors were detected by intravital fluorescent microscope. Results. The GFP-transfected cell lines stably expressed green fluorescence in the absence of G418 over a 36-day period. Compared with the parental cell lines, they exhibited no distinct differences in biological characteristics. MHCC97-HG showed more aggressive invasion and spontaneous metastatic behavior than MHCC97-LG, and even its parental cell line, MHCC97-H (P<0.01). MVD levels induced by MHCC97-HG orthotopic implanted tumors were significantly higher than MHCC97-LG (P<0.01). Real-time angiogenesis and sequential steps of metastasis could be detected clearly under intravital fluorescent microscope. Conclusions. These two stable GFP-expressing HCC cell lines with the same genetic background and different metastatic potential were established, which could be useful models for monitoring metastasis and angiogenesis of HCC. [ABSTRACT FROM AUTHOR]

Purpose. The MHCC97 cell line contains two clones with high (MHCC97-H) and low (MHCC97-L) metastatic potentials, for which the pulmonary metastatic rate was 100% vs 40% between the two human hepatocellular carcinoma (HCC) clones. In an effort to elucidate the mechanism of organ-specific metastasis, we studied the effect of lung extracts from C57BL/6 mice on migration and invasion using the MHCC97 cell line. Methods. Determination of migration and invasion induced by lung extracts to MHCC97 cell lines was examined by chemoinvasion assay. The organization of cytoskeleton was tested using filamentous actin (F-actin) polymerization assay and flow cytometry. The activity of matrix metalloproteinase (MMPs) was analyzed by zymogram. Fluorescence double staining was employed for MMPs and F-actin colocalization in MHCC97-H cells induced by lung extracts. Results. The number of cells in response to extracts of lung, liver, kidney, and spleen in MHCC97-H cells was 64±10, 6±2, 22±4, and 3±1, respectively. Of the extracts, lung extracts showed significant differences to promote the migratory and invasive ability for MHCC97-H cells(p<0.001). The number of cells in response to lung extracts was threefold higher in MHCC97-H than that of cells in MHCC97-L (p<0.001). Confocal laser scan microscope of MHCC97-H cells and MHCC97-L cells stimulated with lung extracts revealed pseudopodia formation around the cell front at the indicated time point. With the time increasing, the pseudopodia formation became increasingly more obvious and distinct. Compared with unstimulated cells, analysis of FACS showed a transient 1.9-fold and 1.7-fold increase in F-actin within 30 s in MHCC97-H cells and MHCC97-L cells, respectively. Confocal laser scan microscopy of MHCC97-H cells stimulated in suspension with lung extracts revealed intense F-actin staining in the periphery of the cells and redistribution of F-actin towards a leading edge. After the cells were incubated with lung extracts, not only expressions of active and latent form of MMP-9 were upregulated, but that of latent form of MMP-2 was increased in the MHCC97-H cells and MHCC97-L cells. The levels of latent and active form of MMP-9(18.8±1.2, 100.1±1.1), and latent form of MMP-2(22.4±1.3) were much higher in MHCC97-H cells than those of MHCC97-L cells, which were 7.8±0.3, 40.8±2.2, and 8.2±0.4, respectively. MMP-9 was mainly localized perinuclear pool when the MHCC97-H cells were incubated with serum-free medium. After the cells were stimulated with lung extracts, MMP-9 were expressed and colocalized with F-actin at the front of extending pseudopodia. Conclusions. Our results indicate that the expression of matrix metalloproteinase and the pseudopodia formation in MHCC97-H cells may correlate to the metastatic potential; thus, the host environment may contribute to the preferential metastasis of HCC cells to the lung depending on the high level of MMP-9 and migratory ability. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the mechanism of interferon alpha (IFN-α) on inhibition of metastasis and recurrence of hepatocellular carcinoma (HCC). Nude mice bearing human HCC xenografts with high metastatic potential (LCI-D20) underwent curative resection of tumors on postimplant day 11. IFN-α was begun the next day at different dosages given subcutaneously for 35 consecutive days; normal saline solution was injected into the control mice. The mice were killed 48 hours after the final treatment, and the parameters were evaluated. The HCC intrahepatic recurrence rate, the size of the recurrent lesions, the rate of lung metastasis, the serum vascular endothelial growth factor level, and the microvessel density (immunohistochemistry) were as follows: 100%, 2136±794 mm3(mean±standard deviation), 100%, 265.7±154.7 pg/ml, and 144±37/HP, respectively, in the control mice, whereas these same values were 62.5%, 89±45 mm3, 12.5%, 53.3±9.9 pg/ml, and 86±25/HP, respectively, in the IFN-α 1.5×107U/kg treatment group (P<0.05) and 26.7%, 46±21 mm3, 0%, 65.2±17.9 pg/ml, and 39±14/HP in the IFN-α 3×107U/kg treatment group, respectively (P<0.05). However, a significant difference was not found in the serum levels of basic fibroblast growth factor among the control and IFN-α treatment groups. IFN-α inhibits metastasis and recurrence of human HCC after curative resection in nude mice mediated by antiangiogenesis through downregulating expression of vascular endothelial growth factor but not basic fibroblast growth factor. [Copyright &y& Elsevier]

Purpose. Two hepatocellular carcinoma (HCC) cell clones named MHCC97-H and MHCC97-L with different metastatic potential have recently been established from the same parent cell line MHCC97 in our institute. The cytogenetic alterations of these two clones were investigated in this study to explore the possible clues to the mechanism involved in HCC metastasis. Methods. Their chromosomal aberrations were analyzed with comparative genomic hybridization (CGH), chromosome-specific painting, and two-color fluorescence in situ hybridization (FISH). Results. The aberrations were found in a total of 17 chromosomes, and six kinds of the aberrations including gains of 1q, 7q, 8q, 20, and the losses of 8p23, 21q were found both in the two cell clones and their parent cell line MHCC97. Using modified CGH, with the DNA of MHCC97-L as control to test the MHCC97-H clone, the loss of 8p23 and the gain of 1q31–32, 8q21.3–22, 13q22, 17q22 were highlighted, and the most significant finding was on chromosome 8. Dual color FISH combining a pericentromeric probe and a BAC probe mapping at 8q23.1 was then performed to verify this result, and the signal ratios of the BAC to centromere were 1.43 in MHCC97-H and 1.45 in MHCC97-L, confirming the over-representations at 8q in both cells. Another interesting finding in the dual-color metaphase FISH was the intrachromosomal translocation of 8q to 8p (looked like an isochromosome 8) and non-reciprocal translocation of part of 8q to 4q, which was further clarified and proved by the FISH with whole chromosome 8 painting probe. Conclusions. The high copies amplification on 8q, the formation of isochromosome 8, non-reciprocal translocation of partial 8q to 4q, and loss of 8p occurred at the same time and are the characteristic chromosomal aberrations of the two cell clones. The chromosome 8p, especially 8p23, might harbor some novel genes related to the HCC metastasis. [ABSTRACT FROM AUTHOR]

To understand the molecular mechanisms of metastasis in hepatocellular carcinoma (HCC), it is necessary to identify the accumulating genetic alterations during its progression as well as those responsible for the acquisition of metastatic potential in cancer cells. In our previous study, using comparative genomic hybridization (CGH), we found that loss on chromosome 8p is more frequent in metastatic lesions than in matched primary tumors of HCC. Thus, 8p deletion might contribute to HCC metastasis. To narrow the location of metastasis-related alteration regions, we analyzed 22 primary and matched metastatic lesions of HCC by genome-wide microsatellite analysis. Common regions with high levels of allelic imbalance (AI) were identified on 17p, 8p11-cen, 8p21-23, 4q32-qter, 4q13-23, 16q, and 1p33. Regions with increased AI in metastatic lesions were 8p23.3, 8p11.2, 17p11.2-13.3, 4q21-22, 4q32-qter, 8q24.1, 9p11, 9q31, 11q23.1, 13q14.1-31, 13q32-qter, 16p13.3, 16q13, 16q22, and 19p13.1, and these were considered to be related to the metastasis phenotype. Among them, loss on 8p was again proved to be related to progression and metastasis of HCC, and 8p23.3 and 8p11.2 were two likely regions harboring metastasis-related genes. It was also shown for the first time in HCC that AI of 19p13.1 might also be related to metastatic potential. These results provide some candidate regions for further study to identify putative genes suppressing metastasis of HCC. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies. Its high mortality rate is mainly a result of intra-hepatic metastases. We analyzed the expression profiles of HCC samples without or with intra-hepatic metastases. Using a supervised machine-learning algorithm, we generated for the first time a molecular signature that can classify metastatic HCC patients and identified genes that were relevant to metastasis and patient survival. We found that the gene expression signature of primary HCCs with accompanying metastasis was very similar to that of their corresponding metastases, implying that genes favoring metastasis progression were initiated in the primary tumors. Osteopontin, which was identified as a lead gene in the signature, was over-expressed in metastatic HCC; an osteopontin-specific antibody effectively blocked HCC cell invasion in vitro and inhibited pulmonary metastasis of HCC cells in nude mice. Thus, osteopontin acts as both a diagnostic marker and a potential therapeutic target for metastatic HCC. [ABSTRACT FROM AUTHOR]

Among various immunotherapeutic approaches, interleukin-12 (IL-12) is particularly appealing because of its superior antitumor effects, which have been demonstrated in preclinical as well as clinical studies. However, IL-12 therapy was often accompanied by severe side effects due mainly to the supranormal induction of interferon-γ. To optimize the therapeutic efficacy and lower the side effects of IL-12, we have investigated the antitumor activity of combined IL-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene therapy in a highly malignant and poorly immunogenic murine hepatocellular carcinoma model. Using a versatile hydrodynamics-based DNA delivery method, we showed that the combined gene delivery of IL-12 and GM-CSF induced very strong antitumor cellular immunity and achieved significant therapeutic efficacy, whereas each cytokine gene alone yielded appreciable but less effects. We also observed that the combined therapy induced lower levels of interferon -γ than did IL-12 alone. These results suggest that combined IL-12 and GM-CSF therapy can render a stronger antitumor effect as well as lowering potential side effects. [ABSTRACT FROM AUTHOR]

Based on the hydrodynamics, the airflow exciting-vibration force of control stage of steam turbine is studied by using the momentum theorem. A formulation for calculating the air exciting-vibration force of the control stage of steam turbine is deduced first by using theoretical analysis method and taking all the design factors of vane and nozzles into consideration. Moreover, the exciting-vibration forces in different load cases are discussed respectively. [ABSTRACT FROM AUTHOR]

Studies the effect of TT virus (TTV) infection on hepatocellular carcinoma development. Prevalence of viral infections in a Euro-Asian series of hepatocellular carcinoma samples; Detection of DNA viruses; Characterization of TTV infection.

One new pyrrole alkaloid 2-[2-formyl-5-(methoxymethyl)-1 H-pyrrol-1-yl]acetic acid ( 1), together with two known ones, 4-[2-formyl-5-(methoxymethyl)-1 H-pyrrol-1-yl]butanoic acid ( 2) and 4-[2-formyl-5- (hydroxymethyl)-1 H-pyrrol-1-yl]butanoic acid ( 3), were isolated from the fruiting bodies of Leccinum extremiorientale for the first time. Their structures were identified on the basis of 1D and 2D NMR spectroscopy as well as MS. [ABSTRACT FROM AUTHOR]

The repair of the alveolar epithelial barrier is essential for the restoration of normal gas exchange function and homeostasis after lung injury. The normal alveolar epithelium is composed of two types of cells: flat type I cells comprising ∼95% of the gas-exchange surface, and cuboidal type II cells, which secrete surfactant. Upon alveolar injury, some or all of the type II cells proliferate and trans-differentiate into type I cells, thus repairing the epithelial barrier. However, molecular mechanisms of this process are unknown. Here, we utilized a mouse model of lung injury caused by it. Pseudomonas aeruginosa (PA) infection. We observed that the expression of FoxM1, a forkhead transcription factor regulating epithelial cell proliferation, was increased 3-fold specifically in type II cells at 72h post infection, coincident with the cell proliferation phase and preceding the re-annealing of alveolar barrier. To investigate the role of FoxM1, we utilized an alveolar type II cell specific FoxM1 knock-out mouse line. We observed decreased cell proliferation as well as defective alveolar epithelial barrier repair after PA challenge of mice with the mutant background. These findings suggest a critical role of transcription factor FoxM1 in alveolar epithelial barrier repair and mediating the transition from type II to type I cells required for barrier re-annealing. [ABSTRACT FROM AUTHOR]

Patchouli is a tropical medicinal and spice crop with high economic value, and the endophytic microorganism is also one of its important components and can provide new active compounds with medicinal use. In the present study, four new biphenyl compounds named 3- O -demethylaltenuisol (1), (−)-dialtenuisol (5) and (+)-dialtenuisol (6), and altertoxin VII (9), as well as six known related compounds, were isolated from the patchouli (Pogostemon cablin) endophytic fungus Alternaria sp. PfuH1. The structures of the new compounds were elucidated from spectroscopic data, ECD spectra analysis, and ECD calculations. Compounds 5 and 6 are a pair of dimeric axially chiral enantiomers. Compounds 2 , 4 , and 9 showed antibacterial activities against S. agalactiae with MIC values of 9.3, 85.3, and 17.3 μg/mL, respectively, and compound 4 also showed weak antibacterial activity against E. coli with MIC value of 128 μg/mL. Unlabelled Image [ABSTRACT FROM AUTHOR]

The metabolites of the genus Marasmius are diverse, showing good research prospects for finding new bioactive molecules. In order to explore the active metabolites of the fungi Marasmius berteroi, the deep chemical investigation on the bioactive compounds from its cultures was undertaken, which led to the isolation of three new naphthalene compounds dipolynaphthalenes A–B (1,2) and naphthone C (3), as well as 12 known compounds (4–15). Compounds 1, 2, and 4 are dimeric naphthalene compounds. Their structures were elucidated by MS, 1D and 2D NMR spectroscopic data, as well as ECD calculations. Compounds 2–4 and 7 exhibited acetylcholinesterase (AChE) inhibitory activities at the concentration of 50 μg/mL with inhibition ratios of 42.74%, 44.63%, 39.50% and 51.49%, respectively. Compounds 5 and 7,8 showed weak inhibitory activities towards two tumor cell lines, with IC50 of 0.10, 0.076 and 0.058 mM (K562) and 0.13, 0.18, and 0.15 mM (SGC-7901), respectively. [ABSTRACT FROM AUTHOR]

A new benzophenone sesquiterpene dobiniside A ( 1), together with two known compounds, 4′,6-dihydroxy-2,3′,4-trimethoxybenzophenone ( 2) and mangiferin ( 3), were isolated from the root of Dobinea delavayi. The structure of the new compound was determined on the basis of spectroscopic analysis, including 1D, 2D NMR, and FAB-MS techniques as well as by comparison of the spectral data with those of related compounds reported in the literature. Compounds 1-3 were screened for antitumor activity in vitro, and compound 3 was shown to possess antitumor activity with IC value of 7.4 × 10 μM for A-549. [ABSTRACT FROM AUTHOR]

Abstract: Natural inhibitors of fatty acid synthase (FAS) are emerging as potential therapeutic agents to treat cancer and obesity. The bioassay-guided chemical investigation of the hulls of Garcinia mangostana led to the isolation of 13 phenolic compounds (1–13) mainly including xanthone and benzophenone, in which compounds 7, 8, 9, 10, and 11 were isolated from this plant for the first time and compound 9 was a new natural product. These isolates possess strong inhibitory activity of FAS with the IC50 values ranging from 1.24 to 91.07μM. The study indicates that two types of natural products, xanthones and benzophenones, could be considered as promising FAS inhibitors. [Copyright &y& Elsevier]

Abstract: Volvalerenone A (1), a new type of mononorsesquiterpenoid with an unprecedented 5/6/6 tricyclic ring system, was isolated from the roots of Valeriana officinalis, the official species of valerian used in Europe. The structure of volvalerenone A was elucidated based on its spectroscopic and single-crystal X-ray crystallography data. The absolute configuration was assigned by the computational method. A possible biosynthetic pathway of volvalerenone A was also proposed. Preliminary biological studies showed that volvalerenone A had weak inhibitory activity on acetylcholine esterase (AChE), and no enhancing activity on nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells was observed at 50μM. [Copyright &y& Elsevier]

The nonlinear photoinduced anisotropy with large birefringence in a bacteriorhodopsin/polymer composite (bR/PC) film was observed. The contrast ratio, a ratio of the maximum to the minimum intensity of transmitted probe light through the bR/PC film within the linear gray scale range could reach ∼350:1. An all-optical image display in different colors was performed. The intensity of the transmitted signal could be modulated by adjusting the multibeam polarization states and intensities. Therefore, the positive image, negative image, and image erasure in display were demonstrated. [ABSTRACT FROM AUTHOR]

A high adsorption capacity (1172.25 mg/g) and fast uptake (98.9% removal within 3 min) of Ag(I) as well as acid resistance (pH = 0.4) were established using sea-urchin-like Bi 2 S 3 hollow microspheres, which make the adsorbent promising for actual applications in water (especially highly acidic) treatment. • 98.9% of Ag ions can be removed within 3 min. • The maximum adsorption capacity of Ag(I) can reach up to 1177.50 mg/g. • The effective removal of Ag(I) were carried out over a broad pH range (from 0.4 to 6). • High-quality Bi 2 S 3 hollow microspheres were prepared on large scale. In this study, we report that the high-quality sea-urchin-like Bi 2 S 3 hollow microspheres (denoted as SUBHM), prepared on a large scale by a simple hard-templated engaged polyol process, were used to remove silver ions under extreme pH conditions. The adsorption of silver ions (Ag(I)) as a function of time, solution pH, temperature and initial Ag(I) concentration was studied by batch experiments. Various characterization tools, such as X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and UV–Vis absorption spectrophotometry, were applied to confirm the structural and compositional changes of the adsorbents during the removal process. The kinetic studies showed that the adsorption process exhibited a fast adsorption rate (98.9% removal within 3 min and 99.8% removal within 10 min, with a 500 ppm initial concentration), which was described well by pseudo-second-order kinetics. The maximum adsorption capacity of Ag(I) was fitted perfectly by the Langmuir adsorption isotherm method at 298 K and pH 1.22. In addition, SUBHM showed an excellent chemical stability under extreme pH conditions, which led to the effective removal of Ag(I) over a broad pH range (from 0.4 to 6). [ABSTRACT FROM AUTHOR]

The course, tempo and mode of chloroplast genome evolution remain largely unknown, resulting in limited knowledge about how plant plastome gene and genome evolve during the process of recent plant speciation. Here, we report the complete plastomes of 22 closely related Oryza species in chronologically ordered stages and generate the first precise map of genomic structural variation, to our knowledge. The occurrence rapidity was estimated on average to be ~7 insertions and ~15 deletions per Myr. Relatively fewer deletions than insertions result in an increased repeat density that causes the observed growth of Oryza chloroplast genome sizes. Genome-wide scanning identified 14 positively selected genes that are relevant to photosynthesis system, eight of which were found independently in shade-tolerant or sun-loving rice species. psaA seemed positively selected in both shade-tolerant and sun-loving rice species. The results show that adaptive evolution of chloroplast genes makes rice species adapt to diverse ecological habitats related to sunlight preferences. Gao, Liu, Zhang, Li et al. report the complete plastid genome assemblies for 22 closely related species of rice, generating a map of genomic structural variation. They show that plastid gene evolution has helped rice evolve to diverse habitats with different levels of sunlight. [ABSTRACT FROM AUTHOR]

Background: With the development of indirect three-dimensional (3D) printing technology, it is possible to customise individual scaffolds to be used in bone transplantation and regeneration. In addition, materials previously limited to the 3D printing (3DP) process due to their own characteristics can also be used well in indirect 3DP. In this study, customised β-TCP/chitosan scaffolds with the shape of rabbit radial head were produced by indirect 3D printing technology. Methods: Swelling ability, porosity, mechanical characterisation, and degradation rate analysis were performed, and in vitro studies were also implemented to evaluate the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs) on the scaffolds. CCK8 cell proliferation assay kit and alkaline phosphatase (ALP) staining solution were used to study cell proliferation and early ALP content at the scaffold surface. Moreover, the osteogenic differentiation of MSCs on scaffolds was also evaluated through the scanning electron microscopy analysis. Results: β-TCP/chitosan scaffold has good performance and degradation rate, and in vitro cell experiments also confirm that the scaffold has adequate cytocompatibility and bioactivity. Conclusion: This study provides a promising new strategy for the design of customised scaffolds for the repair of complex damaged tissues. [ABSTRACT FROM AUTHOR]

Background: Although the proximal humeral fractures (PHFs) treated with locking plate have been well applied, there are few studies concerning on the serial HSA changes after locking plate placement. The purpose of this retrospective study was to explored the clinical significance of serial HSA changes after surgery.Methods: We retrospectively analyzed the clinical data of 122 patients between January 2012 to December 2016 in our hospital. The serial change of the HSA and Neer's score of 122 patients were recorded and analyzed. Then, we evaluated the HSA changes affected functional recovery in conjunction with medial support (MS). Moreover, multivariable linear regression analysis was performed to identify any potential confounding factors that may influence functional recovery.Results: Of 146 patients, 122 (50 males and 72 females) patients were finally enrolled in our study. Our preliminary data suggested that the most decrease of HSA occurred in the period of 1 to 3 months (p < 0.001) postoperatively, and functional recovery was significantly related with the change of HSA (R2 = 0.647, p < 0.001). The presence of MS plays an important role in maintaining postoperative HSA and restoring function. Moreover, Neer type 4 fracture, the difference between the postoperative HSA (on the injured side) and that of the uninjured side (the ΔHSA), and the HSA change to the end of follow-up were all significantly associated with functional recovery.Conclusions: Serial HSA changes were evident in PHF patients in whom locking plates had been inserted; it is essential to maintain reduction for 1-3 months postoperatively. MS is important in this context and surgeons must maximally restore MS. Furthermore, the functional outcome tended to improve when the HSA of the injured side was restored to a value close to that of the uninjured side. [ABSTRACT FROM AUTHOR]

Sepsis patients that exhibit lung vascular injury and high mortality often suffer from severe pulmonary thrombosis (e.g. disseminated intravascular coagulation), but the beneficial impact of anti-coagulants in clinical trials of these patients is modest or absent. Although the regulation of sepsis-induced thrombosis has been intensely investigated, the converse impact of thrombosis on post-sepsis vascular injury is incompletely understood. The main aims of this study were to reveal the impact of varying severities of pulmonary thrombosis on sepsis-induced lung injury, and to determine whether hypoxia-inducible factor (HIF) 1α in endothelial and myeloid cells moderates inflammatory lung injury following thrombotic insult. We employed a mouse model of lung thrombosis in which different numbers of polystyrene microbeads are intra-venously seeded into the lung microvasculature, before or after i.p. lipopolysaccharide challenge. In microbead-free mice challenged with lipopolysaccharide, platelet depletion resulted in reduced pulmonary thrombosis and enhanced lung injury and inflammation. Administration of i.v. polystyrene microbeads, however, restored the level of pulmonary thrombosis to that found in platelet-replete mice, and protected against depletion-induced lung injury and inflammation. We then showed in wild type mice, that while severe increases in the level of pulmonary micro-occlusion worsened post-sepsis lung injury and inflammation, induction of a mild level of pulmonary micro-occlusion instead improved post-sepsis lung injury and inflammation. We also showed that the beneficial impact of this mild level of pulmonary thrombosis on post-sepsis lung injury and inflammation is dependent upon HIF1α. Furthermore, the same mild level of pulmonary thrombosis could even be induced after sepsis challenge to accelerate the resolution of lung inflammation, while induction of severe levels of pulmonary thrombosis after sepsis challenge delayed lung recovery. The experimental models used in our study enable for the quantitative control of thrombosis in the lung, while the administration of i.v. microbeads represents a unique strategy for the induction of a beneficial level of micro-occlusion to stabilize HIF1α in the lung vasculature and reduce inflammatory lung injury. In summary, our study provides evidence that the induction of a mild level of thrombotic occlusion protects against inflammatory lung injury, a finding that could help to explain the unconvincing efficacy of anti-coagulation in sepsis patients. [ABSTRACT FROM AUTHOR]

Six new phragmalin limonoids, named moluccensin Z1 (1), moluccensin Z2 (2), carapanolide Y (3), tabulalin N (4), chukvelutilide A1 (5), and velutinasin J (6), as well as two known compounds, chukvelutilide A (7) and velutinasin D (8) were isolated from the stems of Chukrasia tabularis A. Juss. The structures of the new compounds 1–6 were confirmed by spectroscopic methods, including IR and HRESIMS, as well as 1D and 2D NMR, and by comparisons with the data of known analogues. All compounds were tested for α-glucosidase and acetylcholinesterase inhibitory activities. However, none of the compounds was active against α-glucosidase and acetylcholinesterase in vitro. [ABSTRACT FROM AUTHOR]

Daphnauranins C–E (compounds 1–3), two sesquiterpenoids and one monoterpenoid were isolated from the roots of Daphne aurantiaca Diels. Daphnauranin C is a 9-O-13 etherified and hydroperoxy-substituted guaiane sesquiterpenoid, daphnauranin D is a guaiane sesquiterpenoid ketal, and daphnauranin E is a monoterpenoid lactone. Their structures were elucidated by comprehensive analyses of MS, 1D NMR, and 2D NMR spectroscopic data. In an anti-feeding activities test, daphnauranins C–E showed activity against male fruit fly with anti-feeding indexes (AI) up to 39.1, 39.2, and 27.8% respectively, at 1 mM. [ABSTRACT FROM AUTHOR]

The original article [1] contains an error in Fig. 5a whereby the Western blot bands representing CyclinD1 have mistakenly been duplicated over the Western blot bands intended to represent SGK. [ABSTRACT FROM AUTHOR]