Previously, we and others showed that HIF-1α transcriptional upregulated Aurora-A was required for disease progression in several tumors. Here, we addressed the clinicopathologic value of Aurora-A and HIF-1α in locally advanced nasopharyngeal carcinoma (NPC). Aurora-A and HIF-1α expression was semi-quantitative evaluated by immunohistochemistry staining in 144 cases from a randomized controlled trial. Among which, 69 patients received neoadjuvant chemotherapy plus concurrent chemoradiotherapy were acted as training set, and 75 cases treated with neoadjuvant chemotherapy plus radiotherapy were utilized as testing set to validate the prognostic effect of Aurora-A and HIF-1α. We found that Aurora-A and HIF-1α were highly expressed in NPC, whereas were deficiency in normal adjacent epithelia. In testing set, Aurora-A overexpression predicted a shortened 5-year overall survival (OS, 59.1% VS 82.5%, P=0.024), progression-free survival (PFS, 44.8% VS 79.8%, P=0.004) and distant metastasis-free survival (DMFS, 43.0% VS 17.3%, P=0.016). Multivariate regression analysis confirmed that Aurora-A was indeed an independent prognostic factor for death, recurrence, and distant metastasis both in testing set and overall patients. Moreover, a positive correlation between Aurora-A and HIF-1α was detected (P=0.037). Importantly, though HIF-1α didn't show any prognostic effect for patient outcome, the subset with Aurora-A and HIF-1α co-overexpression had the poorest OS, PFS and DMFS (all P<0.05). Our results confirmed that Aurora-A was an independent prognostic factor for NPC. Combined Aurora-A with HIF-1α refined the risk definition of patient subset, thus potentially directing locally advanced NPC patients for more selective therapy.

Two new daphnane diterpenoids (1 and 2), together with four known analogues (3-6) were isolated from Trigonostemon xyphophylloides. Their structures were elucidated by spectroscopic analysis. Compounds 1 and 2 were evaluated for in vitro cytotoxic activities against the SPCA-1 (human lung cancer) and BEL-7402 (human hepatocellular carcinoma) cancer cell lines. Trigoxyphin I (2) showed modest cytotoxicity against two tumor cell lines.

We have developed glucose-responsive implantable microdevices for closed-loop delivery of insulin and conducted in vivo testing of these devices in diabetic rats. The microdevices consist of an albumin-based bioinorganic membrane that utilizes glucose oxidase (GOx), catalase (CAT) and manganese dioxide (MnO(2)) nanoparticles to convert a change in the environmental glucose level to a pH stimulus, which regulates the volume of pH-sensitive hydrogel nanoparticles and thereby the permeability of the membrane. The membrane is integrated with microfabricated PDMS (polydimethylsiloxane) structures to form compact, stand-alone microdevices, which do not require tethering wires or tubes. During in vitro testing, the microdevices showed glucose-responsive insulin release over multiple cycles at clinically relevant glucose concentrations. In vivo, the microdevices were able to counter hyperglycemia in diabetic rats over a one-week period. The in vitro and in vivo testing results demonstrated the efficacy of closed-loop biosensing and rapid response of the 'smart' insulin delivery devices.

Various studies on lymphoma microenvironment have demonstrated the prognostic impact of tumor-associated macrophages (TAMs) in patients with B-cell lymphoma. Little is known about the correlation between TAMs and treatment outcome in mature T- and natural killer (NK) cell lymphomas. We analyzed the prognostic relevance of CD68+ TAMs by immunohistochemical analysis in 64 Chinese patients with mature T- and NK-cell lymphomas. Higher number of infiltrated TAMs was significantly related to B symptoms and extranodal involvement (p < 0.05). The TAMs content did not differ significantly between pathological subtypes. Using the mean value of TAMs per high-power field (hpf) as the cutoff point (87/hpf), 36 cases (56.2 %) were categorized as low level of TAMs content and 28 cases (43.8%) as high level. Patients with high level of TAMs content had a worse 5-year overall survival compared to those with low level (28.1 vs. 44.3 %, p = 0.039). In multivariate analysis, TAMs content remained an independent biological variable for survival distinct from the International Prognostic Index (Cox multivariate model, p = 0.009). High TAMs content indicated an adverse overall outcome in mature T- and NK-cell lymphomas. Our results show that expression of stromal TAMs may become a useful marker for prognosis of mature T- and NK-cell lymphomas.

BACKGROUND Accurate prognostication of locally advanced nasopharyngeal carcinoma (NPC) will benefit patients for tailored therapy. Here, we addressed this issue by developing a mathematical algorithm based on support vector machine (SVM) through integrating the expression levels of multi-biomarkers. METHODOLOGY/PRINCIPAL FINDINGS Ninety-seven locally advanced NPC patients in a randomized controlled trial (RCT), consisting of 48 cases serving as training set and 49 cases as testing set of SVM models, with 5-year follow-up were studied. We designed SVM models by selecting the variables from 38 tissue molecular biomarkers, which represent 6 tumorigenesis signaling pathways, and 3 EBV-related serological biomarkers. We designed 3 SVM models to refine prognosis of NPC with 5-year follow-up. The SVM1 displayed highly predictive sensitivity (sensitivity, specificity were 88.0% and 81.9%, respectively) by integrating the expression of 7 molecular biomarkers. The SVM2 model showed highly predictive specificity (sensitivity, specificity were 84.0% and 94.5%, respectively) by grouping the expression level of 12 molecular biomarkers and 3 EBV-related serological biomarkers. The SVM3 model, constructed by combination SVM1 with SVM2, displayed a high predictive capacity (sensitivity, specificity were 88.0% and 90.3%, respectively). We found that 3 SVM models had strong power in classification of prognosis. Moreover, Cox multivariate regression analysis confirmed these 3 SVM models were all the significant independent prognostic model for overall survival in testing set and overall patients. CONCLUSIONS/SIGNIFICANCE Our SVM prognostic models designed in the RCT displayed strong power in refining patient prognosis for locally advanced NPC, potentially directing future target therapy against the related signaling pathways.

In the present study, the complete mitochondrial DNA (mtDNA) sequences of the pig nodule worm Oesophagostomum quadrispinulatum were determined for the first time, and the mt genome of Oesophagostomum dentatum from China was also sequenced for comparative analysis of their gene contents and genome organizations. The mtDNA sequences of O. dentatum China isolate and O. quadrispinulatum were 13,752 and 13,681bp in size, respectively. Each of the two mt genomes comprises 36 genes, including 12 protein-coding genes, two ribosomal RNA and 22 transfer RNA genes, but lacks the ATP synthetase subunit eight genes. All genes are transcribed in the same direction and have a nucleotide composition high in A and T. The contents of A+T are 75.79% and 77.52% for the mt genomes of O. dentatum and O. quadrispinulatum, respectively. Phylogenetic analyses using concatenated amino acid sequences of the 12 protein-coding genes, with three different computational algorithms (maximum likelihood, maximum parsimony and Bayesian inference), all revealed that O. dentatum and O. quadrispinulatum represent distinct but closely-related species. These data provide novel and useful markers for studying the systematics, population genetics and molecular diagnosis of the two pig nodule worms.

In order to obtain the additional benefit of anti-diabetic activity and protective effects of liver injury for diabetes, the anti-diabetic effect and acute oral toxicity of a combination of chromium(III) malate complex (Cr(2)(LMA)(3)) and propolis were assessed. The anti-diabetic activity of the combination of the Cr(2)LMA(3) and propolis was compared with Cr(2)(LMA)(3) and propolis alone in alloxan-induced diabetic mice by daily oral gavage for a period of 2 weeks. Acute oral toxicity of the combination of the Cr(2)LMA(3) and propolis was tested using ICR mice at the dose of 1.0-5.0 g/kg body mass by a single oral gavage and observed for a period of 2 weeks. The results of the anti-diabetic activity of the combination from the aspects of blood glucose level, liver glycogen level, and the activities of aspartate transaminase, alanine transaminase, and alkaline phosphatase indicated that the increased anti-diabetic activity and the protective efficacy of liver injury for diabetes were observed. In acute toxicity study, LD(50)(median lethal dose) value for the combination was greater than 5.0 g/kg body mass. The combination of Cr(2)LMA(3) and propolis might represent the nutritional supplement with potential therapeutic value to control blood glucose and exhibit protective efficacy of liver injury for diabetes and non-toxicity in acute toxicity.

Multitendoned extrinsic muscles of the human hand can be divided into several neuromuscular compartments (NMCs), each of which contributes to the ability of human finger to produce independent finger movements or force. The aim of this study was to investigate the changes in the spatial activation of flexor digitorum superficialis (FDS) during the fingertip force production with non-invasive multichannel surface electromyography (sEMG) technique. 7 healthy Subjects were instructed to match the target force level for 5s using individual index finger (I), individual middle finger (M) and the combination of the index and middle finger (IM) respectively. Simultaneously, a 2 × 6 electrode array was employed to record multichannel sEMG from FDS as finger force was produced. The entropy and center of gravity of the sEMG root mean square (RMS) map were computed to assess the spatial inhomogeneity in muscle activation and the change in spatial distribution of EMG amplitude related to the force generation of specific task finger. The results showed that the area and intensity of high amplitude region increased with force production, and the entropy increased with force level under the same task finger. The findings indicate that the change of spatial distribution of multitendoned extrinsic hand muscle activation is correlated to specific biomechanical functions.

PURPOSE In our previous work, it has been shown that intraperitoneal injection of L-DOPA can inhibit the development of occlusion myopia in guinea pigs, and increase levels of retinal dopamine. The aim of this study was to investigate whether exogenous L-DOPA can be converted into dopamine in cultured retina of guinea pig eyes subjected to visual deprivation, and to evaluate whether müller cells are involved in the processing of retinal dopamine induced by L-DOPA. METHODS Fifty-eight guinea pigs were randomly divided into 2 groups at the age of 4 weeks: normal control and visual deprivation. Form deprivation was induced with translucent eye shields over the right eye, and lasted for ten days. Corneal curvature, refraction and axial length were measured in all animals. In vitro, neuro-retina and müller cell were cultured, and L-DOPA was added to the culture medium at three concentrations: 1цM, 10цM and 100цM. Subsequently, dopamine content was evaluated by high-performance liquid chromatography, and apoptotic cells were identified by TUNEL staining. RESULTS Ten days of occlusion caused the affected eyes to elongate and become myopic in guinea pigs. Compared with the deprivation group, 10цM L-DOPA treament significantly raised dopamine content in cultured retina and müller cells (P<0.05). However, 1цM and 100цM L-DOPA treatment caused no increase in dopamine levels (P>0.05). Apoptotic nuclei were detected in the ganglion cell layer (92.5%±8.3%) and inner nuclear layer (46.8%±9.1%) of cultured retina treated with 100 цM L-DOPA. Moreover, 100 цM L-DOPA also caused apoptosis of retinal müller cells, at a mean rate of 59.4 ±11.3%. CONCLUSION Our results suggest that exogenous L-DOPA can cause an increase in retinal dopamine in form-deprived guinea pig eyes in vitro, and that müller cells are involved in the increase in retinal dopamine.