Nanoparticles are now emerging as a novel class of autophagy activators. Functionalized single-walled carbon nanotubes (f-SWCNTs) are valuable nanomaterials in many industries. This article is designed to assess the autophagic response for f-SWCNTs exposure in vitro and in vivo. A few types of f-SWCNTs were screened in human lung adenocarcinoma A549 cells for the autophagic response and related pathways in vitro. Formation of autophagosomes and LC3-II upregulation were confirmed on the basis of electron microscopy and LC3 western blotting for COOH-CNT, but not for PABS-CNT and PEG-CNT. MTT assay showed marked increase in cell viability, when COOH-CNT was added to cells in the presence of autophagy inhibitor 3MA, ATG6 or TSC2 siRNA. Consistent with the involvement of the Akt–TSC1/2–mTOR pathway, the phosphorylation levels of mTOR, mTOR's substrate S6 and Akt were shown significantly decreased in A549 cells on treatment with COOH-CNT using western blotting. What's more, autophagy inhibitor 3MA significantly reduced the lung edema in vivo. In a word, COOH-CNT induced autophagic cell death in A549 cells through the AKT–TSC2–mTOR pathway and caused acute lung injury in vivo. Inhibition of autophagy significantly reduced COOH-CNT-induced autophagic cell death and ameliorated acute lung injury in mice, suggesting a potential remedy to address the growing concerns on the safety of nanomaterials.

Matrix metalloproteinase (MMP)-2 plays critical roles in tumor development and in the metastasis of multiple cancers, including human oral cavity squamous cell carcinoma (OCSCC). One of the upstream regulators of MMP-2 is FOXM1, which is overexpressed in a microarray dataset of OCSCC. It is interesting that FLJ10540 exhibits similar gene expression profiles with MMP-2 and FOXM1, raising the possibility that these molecules might participate in MMP-2-elicited cancer progression and metastasis of OCSCC. To examine this connection, we first showed that FLJ10540 was significantly overexpressed in OCSCC. A strong FLJ10540 expression was significantly correlated with an advanced tumor node metastasis stage and the cumulative 5-year survival rate. Thus, an elevated FLJ10540 expression is an indicator of poor survival. Functionally, FLJ10540 had the abilities to stimulate cell migration and invasion in oral cancer cells through increased FOXM1 and MMP-2 expressions. Conversely, the depletion of the FLJ10540 expression by small interefering RNAs suppressed the FOXM1 and MMP-2 protein expressions. The suppression of either FLJ10540 or FOXM1 could cause significant inhibition on cell migratory and invasive ability in oral cancer cells. Finally, the immunohistochemical and western blotting analyses of human aggressive OCSCC specimens showed a significant positive correlation among FLJ10540, FOXM1 and MMP-2 expressions. These findings suggest that FLJ10540 is not only an important prognostic factor but also a new therapeutic target in the FLJ10540/FOXM1/MMP-2 pathway for OCSCC treatment.

Hepatocellular carcinoma (HCC) is one of the most malignant human tumours because of its high incidence of metastasis. The mechanisms underlying the metastasis of HCC, however, remain poorly understood. In this study, we performed cDNA microarray analysis to profile gene expression patterns in two subtypes of HCC, solitary large HCC (SLHCC) and nodular HCC (NHCC), which differ significantly in the incidence of metastasis. Among 668 genes that were differentially expressed, we focused on RhoC, whose expression was significantly decreased in SLHCC compared to NHCC. The expression of RhoC in HCC and pericarcinomatous liver tissues (PCLT) was analysed at both the mRNA and protein levels by reverse transcription -polymerase chain reaction (RT -PCR) and Western blotting. In addition, immunohistochemistry was also performed on 94 cases of HCC with follow-up information. Collectively, our data indicate that the expression of RhoC significantly increased in HCC compared to PCLT; extrahepatic metastatic lesions expressed significantly higher levels of RhoC than the corresponding intrahepatic HCC tissues. There is a highly significant correlation of the RhoC expression levels with tumour vein invasion, number of tumour nodes and the status of differentiation. Significantly, the HCC patients with RhoC-positive expression had shorter survival than those with RhoC-negative expression. Together, our findings suggest a strong correlation between the expression of RhoC and HCC metastasis, implicating RhoC as a potential prognosis marker and therapeutic target for HCC.

Using, for the first time, configuration-constrained potential-energy-surface calculations with the inclusion of β6 deformation, we find remarkable effects of the high order deformation on the high-K isomers in 254 No, the focus of recent spectroscopy experiments on superheavy nuclei. For shapes with multipolarity six, the isomers are more tightly bound and, microscopically, have enhanced deformed shell gaps at N = 152 and Z = 100. The inclusion of β6 deformation significantly improves the description of the very heavy high-K isomers.

Our pre-clinical studies demonstrated that intratumoral vaccination with a recombinant oncolytic type 2 adenovirus overexpressing the heat shock protein (HSP)70 protein, designated as H103, can inhibit primary and metastatic tumors through enhanced oncolytic activity and HSPmediated immune responses against shared and mutated tumor antigens. In the pre-clinical studies of local H103 administration, no significant toxicity was observed in the animal trials with mice, cavy or rhesus monkeys. A phase I clinical trial of intratumoral injection of H103 was conducted in the patients with advanced solid tumors. A total of 27 patients were injected intratumorally with H103 in a dose-escalation study from a dose of 2.5 Â 10 7 to 3.0 Â 10 12 viral particles (VPs). The maximum tolerated dose of H103 was not defined. Two patients developed dose-limiting toxicities of grade III fever at the dose of 1.5 Â 10 12 VP and transient grade IV thrombocytopenia at the dose of 3.0 Â 10 12 VP. The common adverse events were mainly mild to moderate (grade I/II) in nature, including fever, mild injection-site reaction, leucopenia, lymphopenia, thrombocytopenia and hypochromia. The objective response (complete response+partial response) to H103-injected tumors was 11.1% (3/27), and the clinical benefit rate (complete response+partial response+minor response+stable disease) was 48.1%. Interestingly, transient and partial regression of distant, uninjected tumors was observed in three patients. The numbers of immune cells (CD4 + and CD8 + T cells, and natural killer cells) were elevated after H103 administration, but without statistical significance. This phase I trial demonstrates that intratumoral administration of H103 can be safely applied to cancer patients and shows promising clinical antitumor activity, warranting a further clinical investigation.

Previous studies have suggested that men and women process emotional stimuli differently. In this study, we examined if there would be any consistency in regions of activation in men and women when processing stimuli portraying happy or sad emotions presented in the form of facial expressions, scenes, and words. A blocked design BOLD functional magnetic resonance imaging paradigm was employed to monitor the neural activities of male and female healthy volunteers while they were presented with the experimental stimuli. The imaging data revealed that the right insula and left thalamus were consistently activated for men, but not women, during emotion recognition of all forms of stimuli studied. To further understand the imaging data acquired, we conducted the protocol analysis method to identify the cognitive processes engaged while the men and women were viewing the emotional stimuli and deciding whether they were happy or sad. The findings suggest that men rely on the recall of past emotional experiences to evaluate current emotional experiences. This may explain why the insula, a structure important for self-induced or internally generated recalled emotions, was consistently activated in men while processing emotional stimuli. Our findings suggest possible gender-related neural responses to emotional stimuli. Keywords: emotion; gender; functional magnetic resonance imaging; neuroscience; neuropsychology; emotion recognition It is a common belief that women are more emotional than men. Do men and women, then, process emotional stimuli differently? Sex differences in brain anatomy 1,2 and cognition 3,4 have been increasingly documented. For example, Gur et al 5 observed that women have larger orbital frontal cortices than men and speculated that women have greater tissue volume available for modulating amygdala input leading to gender differences in emotional behavior, particularly aggression. However, studies addressing sex differences in neural activity associated with processing emotional stimuli remain scarce.Kesler/West et al 6 used fMRI to investigate explicit processing of facial emotions including happiness and sadness. They observed that men showed greater left hemispheric activation when observing sad faces than when observing happy faces. No such differences between the emotions in either hemisphere existed among women. Lane et al 7 used PET to study the neural correlates of pleasant and unpleasant emotions, and observed both common and unique components of the neural networks mediating the emotions in healthy women. Canli et al 8 studied sex differences in the neural basis of emotional memories and observed that women had significantly more brain regions than men in which greater activation correlated with both emotional-intensity ratings and better recognition memory for the most emotionally intense picture selected from the International Affective Picture Series (IAPS) 9 and by successful encoding of that experience into long-term memory. In a prior study, Lee et al 10 examined the effect of sex on ...

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We investigate the influence of deformation on the possible occurrence of long-lived K isomers in Hf isotopes around N = 116, using configuration-constrained calculations of potential-energy surfaces. Despite having reduced shape elongation, the multi-quasiparticle states in 186,188 Hf remain moderately robust against triaxial distortion, supporting the long expected occurrence of exceptionally long-lived isomers. The calculations are compared with available experimental data.PACS numbers: 23.20.Lv, 23.35.+g Atomic nuclei have special stability at some proton or neutron numbers named magic numbers. Analogously, there exist some K-magic (K is the total angular momentum projection onto the symmetry axis of a deformed nucleus) numbers associated with exceptionally long-lived high-K isomers [1,2]. Such isomers are formed through broken-pair or multi-quasiparticle (multi-qp) excitations. The long half-life usually originates from a combination of relatively-low excitation energy, high K value and welldeformed axially-symmetric shape. These factors favor the conservation of the K quantum number and hence the hindrance of decay to low-K states. The best known K-magic number is probably Z = 72 where K π = 8 − isomers with the configuration π 2 {7/2 + [404] ⊗ 9/2 − [514]} systematically occur in 170−184 Hf, with half-lives ranging from nanoseconds to hours [3,4]. The neutron number N = 106 is another well-known K-magic number. Here T 1/2 >1-µs K π = 8 − isomers with the configuration ν 2 {7/2 − [514] ⊗ 9/2 + [624]} are observed from 174 Er to 188 Pb [5]. These scarce long chains of isomers provide unique opportunities for systematic study. The doubly K-magic nucleus 178 Hf manifests itself with the occurrence of a 31-yr K π = 16 + isomer based on the coupling ν 2 8 − ⊗ π 2 8 − . The possible stimulated release of the stored energy (2.4 MeV) in the isomer has been associated with proposals for a clean reservoir of nuclear energy and γ-ray lasers [1, 2, 6].Exceptionally long-lived isomers have been predicted to also occur in neutron-rich Hf isotopes due to favorable conditions, i.e., low energy and high K value [2,7,8] However, another important factor, deformation, for the emergence of K isomers could be much different between 178 Hf and the nuclei around 188 Hf. With neutron number N = 106 at the mid-shell between spherical magic numbers 82 and 126, 178 Hf is well deformed, having a shape that favors the formation of long-lived isomers. In contrast, a reduced shape elongation is expected in 188 Hf because the neutron number N = 116 is far away from the mid-shell. Generally, a smaller β 2 deformation is more susceptible to shape fluctuation towards triaxiality that induces K mixing. It is still an open question to what extent the deformation influences the occurrence of exceptionally long-lived K-isomers in neutron-rich Hf isotopes. In the present work, we investigate these high-K isomeric states using configuration-constrained calculations of potential-energy surfaces (PES) [11,12], a model that properly treats the ...