First observation of 28O.

Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Z ratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10-21 s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z = 8 and N = 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called 'doubly magic' nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N = 20 shell structure.

[Genomic investigation of human Streptococcus suis infection in Shandong Province].

To investigate Streptococcus suis (S.suis) isolated from patients in Shandong province using genomic epidemiology and pathogenologic analysis. To provide the foundation to establish reasonable and accurate prevention and control measures of human S. suis infection. Molecular typing, whole genome phylogenetic tree, virulence gene typing, antibiotic resistance profile and mobile genetic elements carrying antibiotic resistance genes of isolated S. suis strains were investigated. The pathogenicity of isolated strains was also evaluated by comparing their capacity to induce pro-inflammatory cytokine production in vitro. S. suis infections in Shandong province were predominantly due to serotype 2 and sequence type 1 strains. The major symptoms were meningitis. The studied strains could be divided into five lineages. All strains belong to highly pathogenic type in Shandong province,Strains from lineage 2 possessed higher capacity to stimulate pro-inflammatory cytokine production than other strains did, even though other strains belong to highly pathogenic strains. In addition, multiple antibiotic resistance genes and corresponding mobile genetic elements werewidespread in S. suis strains from Shandong province, except strains from lineage 3. High diversities in genome, evolutionary path and pathogenicity of S. suis strains from Shandong province were revealed. It was necessary to surveillant the S. suis strain in genomic level.

Two-Neutron Halo is Unveiled in

We report the measurement of reaction cross sections (σ_{R}^{ex}) of ^{27,29}F with a carbon target at RIKEN. The unexpectedly large σ_{R}^{ex} and derived matter radius identify ^{29}F as the heaviest two-neutron Borromean halo to date. The halo is attributed to neutrons occupying the 2p_{3/2} orbital, thereby vanishing the shell closure associated with the neutron number N=20. The results are explained by state-of-the-art shell model calculations. Coupled-cluster computations based on effective field theories of the strong nuclear force describe the matter radius of ^{27}F but are challenged for ^{29}F.

Development and validation of a gene expression test to identify hard-to-heal chronic venous leg ulcers.

BACKGROUND: Chronic venous leg ulcers pose a significant burden to healthcare systems, and predicting wound healing is challenging. The aim of this study was to develop a genetic test to evaluate the propensity of a chronic ulcer to heal. METHODS: Sequential refinement and testing of a gene expression signature was conducted using three distinct cohorts of human wound tissue. The expression of candidate genes was screened using a cohort of acute and chronic wound tissue and normal skin with quantitative transcript analysis. Genes showing significant expression differences were combined and examined, using receiver operating characteristic (ROC) curve analysis, in a controlled prospective study of patients with venous leg ulcers. A refined gene signature was evaluated using a prospective, blinded study of consecutive patients with venous ulcers. RESULTS: The initial gene signature, comprising 25 genes, could identify the outcome (healing versus non-healing) of chronic venous leg ulcers (area under the curve (AUC) 0·84, 95 per cent c.i. 0·73 to 0·94). Subsequent refinement resulted in a final 14-gene signature (WD14), which performed equally well (AUC 0·88, 0·80 to 0·97). When examined in a prospective blinded study, the WD14 signature could also identify wounds likely to demonstrate signs of healing (AUC 0·73, 0·62 to 0·84). CONCLUSION: A gene signature can identify people with chronic venous leg ulcers that are unlikely to heal.

Critical Velocity in the Presence of Surface Bound States in Superfluid

A microelectromechanical oscillator with a gap of 1.25 µm was immersed in superfluid ^{3}He-B and cooled below 250 µK at various pressures. Mechanical resonances of its shear motion were measured at various levels of driving force. The oscillator enters into a nonlinear regime above a certain threshold velocity. The damping increases rapidly in the nonlinear region and eventually prevents the velocity of the oscillator from increasing beyond the critical velocity which is much lower than the Landau critical velocity. We propose that this peculiar nonlinear behavior stems from the escape of quasiparticles from the surface bound states into the bulk fluid.

Tissue invasion and metastasis: Molecular, biological and clinical perspectives.

Cancer is a key health issue across the world, causing substantial patient morbidity and mortality. Patient prognosis is tightly linked with metastatic dissemination of the disease to distant sites, with metastatic diseases accounting for a vast percentage of cancer patient mortality. While advances in this area have been made, the process of cancer metastasis and the factors governing cancer spread and establishment at secondary locations is still poorly understood. The current article summarizes recent progress in this area of research, both in the understanding of the underlying biological processes and in the therapeutic strategies for the management of metastasis. This review lists the disruption of E-cadherin and tight junctions, key signaling pathways, including urokinase type plasminogen activator (uPA), phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene (PI3K/AKT), focal adhesion kinase (FAK), ß-catenin/zinc finger E-box binding homeobox 1 (ZEB-1) and transforming growth factor beta (TGF-ß), together with inactivation of activator protein-1 (AP-1) and suppression of matrix metalloproteinase-9 (MMP-9) activity as key targets and the use of phytochemicals, or natural products, such as those from Agaricus blazei, Albatrellus confluens, Cordyceps militaris, Ganoderma lucidum, Poria cocos and Silybum marianum, together with diet derived fatty acids gamma linolenic acid (GLA) and eicosapentanoic acid (EPA) and inhibitory compounds as useful approaches to target tissue invasion and metastasis as well as other hallmark areas of cancer. Together, these strategies could represent new, inexpensive, low toxicity strategies to aid in the management of cancer metastasis as well as having holistic effects against other cancer hallmarks.

Anomalous Damping of a Microelectromechanical Oscillator in Superfluid

The mechanical resonance properties of a microelectromechanical oscillator with a gap of 1.25 µm was studied in superfluid ^{3}He-B at various pressures. The oscillator was driven in the linear damping regime where the damping coefficient is independent of the oscillator velocity. The quality factor of the oscillator remains low (Q≈80) down to 0.1T_{c}, 4 orders of magnitude less than the intrinsic quality factor measured in vacuum at 4 K. In addition to the Boltzmann temperature dependent contribution to the damping, a damping proportional to temperature was found to dominate at low temperatures. We propose a multiple scattering mechanism of the surface Andreev bound states to be a possible cause for the anomalous damping.

[Curative effect analysis of posterior decompression and internal fixation for spinal metastases epidural spinal cord compression].

OBJECTIVE: To explore the effects of posterior decompression and internal fixation for spinal metastases epidural spinal cord compression (MESCC) and analyze the related factors of postoperative ambulation function. METHODS: Clinical data of 67 cases with MESCC who received thoracic posterior decompression and internal fixation in our department from January 2006 to December 2014 was retrospectively analyzed. Information about patients' age, gender, pathological type of primary tumor, Karnofsky performance status (KPS) score, pre-operative and postoperative visual analogue scale, preoperative Frankel grade, pre-operative and postoperative imaging characteristics (number of thoracic vertebrae metastases, location, compression fractures of vertebral bodies), time of movement dysfunction and survival was collected. RESULTS: At the end of the follow-up of 67 cases, 57 cases were dead, 10 cases were alive, and the median survival was 8.1 months (1.2-91.9 months).38 cases (67%) died within one year, 50 cases (88%) died within two years. Visual analogue scale of preoperative and postoperative dropped from (5.67±1.67) points to (2.11±1.39) points (P<0.001), 38 (53%) patients' Frankel grade improved at least one grade. Among the 34 cases who were unable to walk, 15 cases regained ability of ambulation after surgery. The patients with KPS scores greater than 80 points and/or had preoperative ambulation ability, tended to have better postoperative ambulatory function. CONCLUSIONS: Posterior decompression and internal fixation for MESCC is effective, and can effectively relieve pain and spinal cord compression, improve neurological function and the quality of life. The ambulatory functional outcomes after surgery are dependent on KPS scores, the occurrence time of neurological dysfunction, preoperative ambulatory status.

[Comparison of curative effect and prognosis analysis of patients with spinal metastases treated by percutaneous vertebroplasty combined with postoperative radiotherapy and radiotherapy alone].

Objective: To evaluate the efficacy of percutaneous vertebroplasty(PVP) combined with postoperative radiotherapy and radiotherapy alone in the treatment of spinal metastatic tumors and to evaluate the prognostic factors for survival. Methods: From December 2011 to December 2015, according to the choice of treatment, patients in group A(60 cases) were treated with PVP combined with postoperative radiotherapy and those in group B(50 cases) underwent radiotherapy alone, age, sex, primary tumor type , and other basic characteristics were analyzed in both groups in department of orthopedics and radiotherapy department, 307 Hospital of the People's Liberation Army. The pain visual analogue scale(visual analogue scale, VAS), tumors of the spine instability score(the spinal instability neoplastic score and sins), physical status score(Karnofsky performance score and KPS) were used to evaluate pain, spinal stability improvement and physical condition. Kaplan-Meier was used to analyze the survival rates of two groups of patients and the influence of primary tumor types on the survival of patients; Cox proportional hazard model was used to calculate the correlations between survival and visceral metastases, system medical treatment, vertebral number before treatment and physical condition. Results: There was no significant difference in baseline data between the two groups(P>0.05). The VAS in the group A was significantly lower than the scores in the group B at 1 month, 3 months, 6 months, and 12 months after surgery. The SINS score dropped from(7.8±1.2) to(6.3±0.9)(1 month), (6.1±0.8)(3 months) in patients with PVP combined with postoperative radiotherapy(P<0.05), the SINS score of radiotherapy patients simply dropped from(7.6±0.9) to(7.4±0.7)(1 month), (7.3±0.6)(3 months), and there was no statistically significant difference(P=0.12). The survival rates of 6 months, 1 years, and 3 years were similar between two groups(P>0.05). The influence of different types of primary tumors on the survival time of the patients was statistically significant(P<0.05). Multiple analysis showed that the internal organs metastasis, systemic medical treatment, the number of vertebral bodies and the physical condition were the important prognostic factors of the survival in patients with spinal metastases. Conclusion: PVP combined with postoperative radiotherapy for spinal metastases is better than radiotherapy alone in the treatment of relieving pain, maintaining the stability of vertebral body and improving the quality of life of patients. Survival prognosis was similar in two groups. The types of primary tumors, visceral metastasis, systemic medical treatment, the number of vertebral bodies and the physical condition are important prognostic factors in the survival of patients with spinal metastases.

Multivariate analysis of molecular markers in peripheral blood associated with recurrence and metastasis of hepatocellular carcinoma.

Invasion, metastasis, and recurrence are the most common causes of death in patients with hepatocellular carcinoma (HCC) and are therefore critical factors for both therapy and prognosis. Current methods for diagnosis of HCC rely mainly on serological markers such as alpha-fetoprotein and liver enzymes, together with physical assessment and imaging techniques. The availability of more accurate serum markers may facilitate screening and early diagnosis, which will improve prognosis. This retrospective cohort analysis included 50 consecutive patients with cirrhosis and single or multifocal HCC and 40 control subjects with no liver disease or risk factors for viral hepatitis. Expression of epidermal growth factor-like domain 7 (EGFL7), osteopontin (OPN), and prostaglandin E2 (PGE2) were detected using an enzyme-linked immunosorbent assay. The mean serum levels of EGFL7, OPN, and PGE2 in the HCC group were 132.11 pg/mL, 11.77 ng/mL, and 179.37 pg/mL, respectively, which were all significantly higher than the levels in the control group (23.03 pg/mL, 2.31 ng/mL, and 47.36 pg/mL, respectively; P < 0.001). Serum levels of EGFL7, OPN, and PGE2 levels may thus be useful for screening and surveillance of HCC among high-risk populations, and have the potential to improve prognosis of these patients.

Death-associated protein-3, DAP-3, correlates with preoperative chemotherapy effectiveness and prognosis of gastric cancer patients following perioperative chemotherapy and radical gastrectomy.

BACKGROUND: DAP3 is a member of the death-associated protein (DAP) family and is characterised by proapoptotic function. It is involved in both exogenous and endogenous apoptotic pathways. In our previous studies, apoptotic level was found to be correlated with the effectiveness of preoperative chemotherapy. The effectiveness of preoperative chemotherapy was also associated with the overall effectiveness of the combined therapy and prognosis. The present study aimed to investigate the role of DAP3 in the evaluation of preoperative chemotherapy effectiveness and its ability to predict prognosis in gastric cancer. METHODS: Quantitative PCR and immunohistochemistry staining were performed in 87 patients who received combined therapy. Knockdown of DAP3 was conducted in gastric cancer cell lines to investigate its impact on cell growth, migration, adhesion and invasion. Tolerance to chemotherapy agents was determined by assessing apoptosis and caspase-3. RESULTS: Higher DAP3 expression in gastric tumours was correlated with better prognosis. Knockdown of DAP3 expression promoted cell migration and enhanced resistance to chemotherapy by inhibiting apoptosis. CONCLUSION: DAP3 is a potential molecular marker for response to preoperative chemotherapy and for predicting prognosis in gastric cancer patients treated with neoadjuvant chemotherapy and gastrectomy.

AR mRNA stability is increased with AR-antagonist resistance via 3'UTR variants.

Advanced prostate cancer is often treated with AR antagonists which target the androgen receptor (AR) on which the growth of the tumour depends. Prostate cancer often develops AR-antagonist resistance via a plethora of mechanisms, many of which are as yet unknown, but it is thought that AR upregulation or AR ligand-binding site mutations, may be responsible. Here we describe the production of cell lines based on LNCaP and VCaP, with acquired resistance to the clinically relevant AR antagonists, bicalutamide and enzalutamide. In these resistant cells, we observed, via RNA-seq, that new variants in the 3'UTR of the AR mRNA were detectable and that the levels were increased both with AR-antagonist treatment and with hormonal starvation. Around 20% of AR transcripts showed a 3 kb deletion within the 6.7 kb 3'UTR sequence. Actinomycin D and luciferase fusion studies indicated that this shorter mRNA variant was inherently more stable in anti-androgen-resistant cell lines. Of additional interest was that the AR UTR variant could be detected in the sera of prostate cancer patients in a cohort of serum samples collected from patients of Gleason grades 6-10, with an increasing level correlated to increasing grade. We hypothesise that the shorter AR UTR variant is a survival adaptation to low hormone levels and/or AR-antagonist treatment in these cells, where a more stable mRNA may allow higher levels of AR expression under these conditions.

The mRNA expression of SETD2 in human breast cancer: correlation with clinico-pathological parameters.

BACKGROUND: SET domain containing protein 2 (SETD2) is a histone methyltransferase that is involved in transcriptional elongation. There is evidence that SETD2 interacts with p53 and selectively regulates its downstream genes. Therefore, it could be implicated in the process of carcinogenesis. Furthermore, this gene is located on the short arm of chromosome 3p and we previously demonstrated that the 3p21.31 region of chromosome 3 was associated with permanent growth arrest of breast cancer cells. This region includes closely related genes namely: MYL3, CCDC12, KIF9, KLHL18 and SETD2. Based on the biological function of these genes, SETD2 is the most likely gene to play a tumour suppressor role and explain our previous findings. Our objective was to determine, using quantitative PCR, whether the mRNA expression levels of SETD2 were consistent with a tumour suppressive function in breast cancer. This is the first study in the literature to examine the direct relationship between SETD2 and breast cancer. METHODS: A total of 153 samples were analysed. The levels of transcription of SETD2 were determined using quantitative PCR and normalized against (CK19). Transcript levels within breast cancer specimens were compared to normal background tissues and analyzed against conventional pathological parameters and clinical outcome over a 10 year follow-up period. RESULTS: The levels of SETD2 mRNA were significantly lower in malignant samples (p = 0.0345) and decreased with increasing tumour stage. SETD2 expression levels were significantly lower in samples from patients who developed metastasis, local recurrence, or died of breast cancer when compared to those who were disease free for > 10 years (p = 0.041). CONCLUSION: This study demonstrates a compelling trend for SETD2 transcription levels to be lower in cancerous tissues and in patients who developed progressive disease. These findings are consistent with a possible tumour suppressor function of this gene in breast cancer.

BDNF activates TrkB/PLCγ1 signaling pathway to promote proliferation and invasion of ovarian cancer cells through inhibition of apoptosis.

OBJECTIVE: Abnormal expression and activation of tropomyosin-related kinase receptor B (TrkB) are observed in many pathological conditions, including many types of cancer. We try to explore the relationship between ovarian cancer and Brain-derived neurotrophic factor (BDNF), a ligand of TrkB. MATERIALS AND METHODS: Human ovarian cancer cell line SKOV-3 was used in this study. qPCR, immunohistochemistry, and immunoblot were used to assay BDNF and TrkB expression level. Scratch assay was used to test the cell motility, and transwell assay was used to test the cell migration ability. RESULTS: We found that BDNF promotes the proliferation and invasion of human ovarian cancer SKOV-3 cells depend on the activation of TrkB. To illuminate the downstream pathway of BDNF/TrkB, we silenced AKT1 and PLCγ1 by siRNA. The functional assay showed that activated PLCγ1 signaling pathway is necessary for the proliferation and invasion of cancer cells other than the AKT pathway. Further study showed that PLCγ1 could inhibit the apoptosis of cancer cells. CONCLUSIONS: BDNF triggers TrkB/PLCγ1 signaling pathway to promote proliferation and invasion of ovarian cancer cells through inhibition of apoptosis.

Expression of the WASP verprolin-homologues (WAVE members) in human breast cancer.

BACKGROUND: The WASP family proteins have been indicated to play a vital role in the formation of membrane protrusions required for cell locomotion. WAVE proteins are an important subfamily that also plays a crucial role in actin polymerisation, which is vital to cell migration. However, not much is known about the clinical significance of this subfamily in cancers. We report, for the first time, the expression of the WAVE molecules, at protein and mRNA levels, in human breast cancer. MATERIALS AND METHODS: The expression of the 3 WAVE molecules at the mRNA and protein levels in a cohort of 122 human breast cancers and 32 normal breast tissues were analysed and correlated with the patients' pathological and clinical information as well as outcome (120 months follow-up). RESULTS: All 3 WAVE molecules were detected in mammary tissues. WAVE2 transcripts were expressed in high levels in all breast tumours. Over-expression of WAVE2 was seen in node-positive cases as well as in moderately and poorly differentiated tumours. Also, high levels of WAVE2 expression were associated with death due to disease (p = 0.02) at follow-up. No distinct associations were found between the WAVE1 and WAVE3 transcripts and the breast cancer cells.

Evidence for a tumour suppressive function of IGF1-binding proteins in human breast cancer.

UNLABELLED: The role of the insulin like growth factor (IGF) system in various human malignancies has been well established. The aim of this study was to determine the levels of mRNA expression of insulin-like growth factor-binding protein (IGFBP)-1, -3 and -7 genes in benign and malignant breast tissue and explore their relationship with various prognostic parameters. MATERIALS AND METHODS: Breast cancer tissue (n=127) and normal background tissue (n-33) were prospectively collected and analysed for levels of IGFBP-1, -3 and -7 mRNA using real-time Q-PCR. mRNA levels were then analysed against tumour grade, nodal status, Nottingham prognostic index (NPI)/TNM stage and tumour type. RESULTS: For IGFBP-1 and -3, mRNA expression was higher in normal tissue. This was significant for IGFBP-1 when comparing NPI 3 with NPI 1 (p=0.050) and the normal group (p=0.040). With respect to TNM analysis, there was less IGFBP-1 mRNA when comparing TNM 3 with normal (p=0.017), TNM 1 (p=0.047) and TNM 2 (p=0.019) tumours. This was also found when comparing TNM 4 samples with normal tissue (p=0.017), TNM 1 (p=0.046) and TNM 2 (p=0.019). For IGFBP-3 mRNA, there was less mRNA when comparing TNM 3 with TNM 1 (p= 0.017) and TNM 2 (p=0.050), and also less mRNA expression when comparing TNM 4 with TNM 1 (p=0.030). For IGFBP-7 mRNA, both TNM 1 (p=0.0077) and TNM 2 (p=0.015) had significantly more expression than TNM 3 samples. CONCLUSION: This study supports the role of IGFBP-1, -3 and -7 as potential tumour suppressor genes in human breast cancer.

Prostate-specific PTen deletion in mice activates inflammatory microRNA expression pathways in the epithelium early in hyperplasia development.

PTen loss is one of the most frequent events in prostate cancer both at the initiation stage and during late stage metastatic development. The mouse model of prostate-specific probasin-mediated Pten deletion leads to prostate intraepithelial neoplasia (PIN) leading to adenocarcinoma. Using this model, we analysed the miR and mRNA transcriptome profile of Pten -/- PIN versus wild type age-matched prostate tissues and analysed the effects of Pten loss on miR expression in the early neoplastic process. At the PIN stage, Pten loss significantly changed the expression of over 20 miRNAs and over 4000 genes. The observed miR expression indicated a strong immunological cohort, which is seen in many human and mouse cancers and is thought to derive from infiltrating B and T immune cells. However, upon in situ hybridisation, these immunologically related miRs did not correlate with immune cell location, and emanated from the prostate epithelium itself and not from the associated immune cells present. Growing Pten -/- prostate cells in culture showed that the overexpressed miRNAs seen in Pten -/- were directly in response to the overactive PI3 kinase pathway and were in part responsible in reducing target gene expression levels. Inhibition of PI3 kinase downstream regulators, or re-introducing wild type Pten cDNA reduced miR overexpression resulting in increased miR target gene expression. MiR inhibitors also showed this pattern, and synergised with an mTORC1 inhibitor. Overall, Pten deletion in the prostate epithelium activated a cohort of inflammation-related miRs usually associated with immune responses from B and T cells. These oncomiRs may then accelerate carcinogenesis.

PDZK1 inhibits the development and progression of renal cell carcinoma by suppression of SHP-1 phosphorylation.

Renal cell carcinoma (RCC) is one of the most aggressive urologic cancers, however, the mechanism on supporting RCC carcinogenesis is still not clear. By using gene expression profile analysis and functional clustering, PDZ domain-containing 1 (PDZK1) was revealed to be downregulated in human clear cell renal cell carcinoma (ccRCC) samples, which was also verified in several independent public ccRCC data sets. Using PDZK1 overexpression and knockdown models in ccRCC cell lines, we demonstrated that PDZK1 inhibited cell proliferation, cell cycle G1/S phase transition, cell migration and invasion, indicating a tumor-suppressor role in the development and progression of ccRCC. Our study further demonstrated that PDZK1 inhibited cell proliferation and migration of ccRCC via targeting SHP-1. PDZK1 was further identified to suppress cell proliferation by blocking SHP-1 phosphorylation at Tyr536 via inhibition of the association between SHP-1 and PLCß3, and then retarding Akt phosphorylation and promoting STAT5 phosphorylation in ccRCC cells. Moreover, the inhibitive effects of PDZK1 on SHP-1 phosphorylation and the tumor growth were verified in vivo by xenograft tumor studies. Accordingly, PDZK1 expression was negatively correlated with SHP-1 activation and phosphorylation, advanced pathologic stage, tumor weight and size, and prognosis of ccRCC patients. These findings have provided first lines of evidences that PDZK1 expression is negatively correlated with SHP-1 activation and poor clinical outcomes in ccRCC. PDZK1 was identified as a novel tumor suppressor in ccRCC by negating SHP-1 activity.