Efficient weakly supervised LIBS feature selection method in quantitative analysis of iron ore slurry.

On-stream analysis of the element content in ore slurry plays an important role in the control of the mineral flotation process. Therefore, our laboratory developed a LIBS-based slurry analyzer named LIBSlurry, which can monitor the iron content in slurries in real time. However, achieving high-precision quantitative analysis results of the slurries is challenging. In this paper, a weakly supervised feature selection method named spectral distance variable selection was proposed for the raw spectral data. This method utilizes the prior information that multiple spectra of the same slurry sample have the same reference concentration to assess the important weight of spectral features, and features selected by this prior can avoid over-fitting compared with a traditional wrapper method. The spectral data were collected on-stream of iron ore concentrate slurry samples during the mineral flotation process. The results show that the prediction accuracy is greatly improved compared with the full-spectrum input and other feature selection methods; the root mean square error of the prediction of iron content can be decreased to 0.75%, which helps to realize the successful application of the analyzer.

Adenovirus 7 Induces Interlukin-6 Expression in Human Airway Epithelial Cells via p38/NF-κB Signaling Pathway.

Human Adenovirus (AdV) infection is very common and usually has a significant impact on children. AdV-induced inflammation is believed to be one of the main causes of severe symptoms. However, an inflammatory response profile in the airway in AdV-infected children is still lacking, and the mechanism underlying AdV-induced inflammation in the airway is also poorly understood. In the current study, we determined the expression of a panel of inflammation cytokines in the airway samples from AdV 7 infected children and further investigated the molecular mechanism underlying AdV 7-induced cytokine expression. Our results showed that eight out of 13 tested inflammatory cytokines were significantly increased in nasal washes of AdV 7-infected children comparing to healthy control, with IL-6 showing the highest enhancement. AdV 7 infection of bronchial epithelial cell line and primary airway epithelial cells confirmed that AdV 7 increased IL-6 mRNA and protein expression in an infection dose-dependent manner. Promoter analysis revealed that AdV 7 infection transactivated IL-6 promoter and a NF-κB binding site in IL-6 promoter was involved in the transactivation. Further analysis showed that upon AdV 7 infection, NF-κB p65 was phosphorylated and translocated into nucleus and bound onto IL-6 promoter. Signaling pathway analysis revealed that p38/NF-κB pathway was involved in AdV 7 infection induced IL-6 elevation. Taken together, our study shows that AdV 7 infection triggers the expression of a range of inflammatory cytokines including IL-6 in the airway of infected children, and AdV 7 enhances IL-6 expression by transactivating IL-6 promoter via p38/NF-κB signaling pathway. Findings of our current study have provided more information toward a better understanding of AdV-induced airway inflammation, which might also benefit the development of intervention strategies.

The Promising Effects of Transplanted Umbilical Cord Mesenchymal Stem Cells on the Treatment in Traumatic Brain Injury.

Many studies have reported the recovery ability of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for neural diseases. In this study, the authors explored the roles of UC-MSCs to treat the traumatic brain injury. Umbilical cord-derived mesenchymal stem cells were isolated from healthy neonatal rat umbilical cord immediately after delivery. The traumatic brain injury (TBI) model was formed by the classical gravity method. The authors detected the behavior changes and measured the levels of inflammatory factors, such as interleukin-lß and tumor necrosis factor-α by enzyme linked immunosorbent assay (ELISA) at 1, 2, 3, 4 weeks after transplantation between TBI treated and untreated with UC-MSCs. Simultaneously, the expression of glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF) were measured by real-time-polymerase chain reaction and ELISA.The authors found that the group of transplantation UC-MSCs has a significant improvement than other group treated by phosphate buffered saline. In the behavioral test, the Neurological Severity Scores of UC-MSCs + TBI group were lower than TBI group (P < 0.05), but not obviously higher than control group at 2, 3, and 4week, respectively. The inflammatory factors are significantly reduced comparison with TBI group (P < 0.05), but both GDNF and BDNF were higher than TBI group (P < 0.05). The results indicated that UC-MSCs might play an important role in TBI recovery through inhibiting the release of inflammatory factors and increasing the expression of GDNF and BDNF.

Detection of K-ras gene mutations in feces by magnetic nanoprobe in patients with pancreatic cancer: A preliminary study.

The present study aimed to investigate the feasibility and effectiveness of detecting K-ras mutation by using magnetic nanoparticles in fecal samples of patients with pancreatic cancer at different stages. The novel methodology of K-ras mutation detection was compared to the existing methodology of cancer antigen (CA)19-9 examination. Patients with pancreatic cancer (n=88), pancreatic benign diseases who displayed chronic pancreatitis (n=35), pancreatic mucinous cyst neoplasms (n=10) and pancreatic serous cyst (n=9) admitted to the Department of Surgery, Jiaxing Second Hospital were enrolled in the present study. Fecal samples were collected from all patients, DNA was extracted and magnetic nanoprobe was then used to detect K-ras mutation. The results obtained using the novel magnetic nanoprobe detection technique showed a K-ras mutation rate of 81.8% (72/88) in the patients with pancreatic cancer and 18.5% (10/54) in patients with pancreatic benign diseases. In patients with pancreatic cancer, the K-ras mutation rate was comparable in stages I + IIA and IIB + III + IV (78.9 vs. 84.0%; P>0.05). The sensitivity and specificity of K-ras mutation for detection of pancreatic cancer was 81.8 and 81.5%, respectively. Sixty-eight pancreatic cancer patients had >37 U/ml CA99 with a sensitivity and specificity for pancreatic cancer detection of 77.3 and 77.8%, which was not significantly lower than detection by the fecal K-ras mutations (P>0.05). Combinational detection of fecal K-ras mutations and serum CA19-9 significantly increased the sensitivity regarding pancreatic cancer detection to 97.7% (P<0.05), while the specificity was not enhanced (80.9%; P>0.05) compared with fecal K-ras mutations or CA19-9 alone. The findings showed that the magnetic nanoprobe is able to detect fecal K-ras mutations in different stages of pancreatic cancer, with comparable sensitivity and specificity to CA19-9 examination for differentiating pancreatic cancer. Furthermore, combined detection of CA19-9 and K-ras mutations has enhanced sensitivity compared with CA19-9 alone.

Photo-controlled aptamers delivery by dual surface gold-magnetic nanoparticles for targeted cancer therapy.

Dual surfaced dumbbell-like gold magnetic nanoparticles (Au-Fe3O4) were synthesized for targeted aptamers delivery. Their unique biological properties were characterized as a smart photo-controlled drug carrier. DNA aptamers targeting vascular endothelial growth factor (VEGF) were assembled onto the surface of Au-Fe3O4 by electrostatic absorption. The binding capacity of the nanoparticles with VEGF aptamers was confirmed by gel electrophoresis. The targeted recognization of ovarian cancer cells by the aptamers-functionalized Au-Fe3O4 nanoparticles (Apt-Au-Fe3O4 NPs) was observed by confocal microscopy. Apt-Au-Fe3O4 was found to bind with SKOV-3 ovarian cancer cells specifically, leading to marked intracellular release of aptamers upon plasmon-resonant light (605nm) radiation, and to enhance the in vitro inhibition against tumor cell proliferation. The results show high potential of Apt-Au-Fe3O4as a targeted cancer hyperthermia carrier by remote control with high spatial/temporal resolution.

Targeted chimera delivery to ovarian cancer cells by heterogeneous gold magnetic nanoparticle.

Efficient delivery of small interfering RNAs (siRNAs) to the targeted cells has remained a significant challenge in clinical applications. In the present study, we developed a novel aptamer-siRNA chimera delivery system mediated by cationic Au-Fe3O4 nanoparticles (NPs). The chimera constructed by VEGF RNA aptamer and Notch3 siRNA was bonded with heterogeneous Au-Fe3O4 nanoparticles by electrostatic interaction. The obtained complex exhibited much higher silencing efficiency against Notch3 gene compared with chimera alone and lipofectamine-siRNA complex, and improved the antitumor effects of the loaded chimera. Moreover, the efficient delivery of the chimera by Au-Fe3O4 NPs could reverse multi-drug resistance (MDR) of ovarian cancer cells against the chemotherapeutic drug cisplatin, indicating its potential capability for future targeted cancer therapy while overcoming MDR.

Aptamer Functionalized Cisplatin-Albumin Nanoparticles for Targeted Delivery to Epidermal Growth Factor Receptor Positive Cervical Cancer.

Targeted nanocarriers may offer a new approach to improve the efficacy and tolerability of cisplatin, which are commonly used to treat cancers as a first line chemotherapy for most types of cancer. In the present study, we have developed EGFR-targeted albumin-cisplatin nanoparticles for tumor targeted delivery of cisplatin. The cisplatin NPs were conjugated with EGFR aptamer, which binded to Hela cells specifically, then taken up by tumor cells through receptor mediated endocytosis. The aptamers accumulate in the tumor and interact with the receptor on the surface of Hela cells, successfully blocked EGF-induced EGFR phosphorylation, exerting its targeting and therapy function. Here we demonstrate that the EGFR aptamer functioned NPs enhanced in vitro antitumor effects and markedly improved its tolerability and in vivo efficacy when compared with free cisplatin and other single treatment. Furthermore, the Apt-Pt NPs treatment resulted in reduced systemic and nephrotoxicity, validated by decreased biodistribution of platinum in the major organs as quantified by ICP-MS. The Apt-Pt NPs provides a remarkable improvement in the drug therapeutic efficacy and tolerability in vivo, and will be generalized as a principle for development of novel nanocarriers for targeted tumor therapy.

[In-Situ Analysis of Solid Steel Samples with Remote Double-Pulse Laser-Induced Breakdown Spectroscopy System].

In order to realize real-time, online monitoring of the component of steel and other metal smelting process, we designed a remote double-pulse laser-induced breakdown spectroscopy (LIBS) analysis system which can realize non-contact remote measurement and component analysis for long distance sample. The paper first tests the system on solid standard steel samples, which provides basis for online monitoring the component of molten steel. The experimental results show：laser focal spot is about 1mm in long distance; double-pulse ablation depth is deeper than single pulse's; the optimum delay of double-pulse is non-consistent in different distances; the enhancement effect of double- pulse in 3.1 m is better than that in 2.1 m，and the maximum enhancement is 5.19 of Ti(Ⅰ) 319.99 nm; the calibration curve of R2 is about 0.99, RSD being less than 5%, RMSE being less than 0.021%, LOD being less than 500 ppm for most elements in 2.1 m, which is better than that in 3.1 m.

Highly efficient Gab2 siRNA delivery to ovarian cancer cells mediated by chitosan-polyethyleneimine nanoparticles.

Malignant bowel obstruction (MBO) is a serious complication which causes high death rate and low quality of life (QOL) for patients diagnosed at an advanced stage of ovarian cancer. RNA interference (RNAi) could be a promising method for the treatment of ovarian cancer and could decrease the morbidity of MBO. Gab2 gene is overexpressed in ovarian cancer compared with normal ovarian tissue, and regulates the migratory behaviors and E-cadherin expression via activation of the PI3K pathway in ovarian cancer cells. Here, chitosan-polyethyleneimine (PEI, Mw 1800) copolymer nanoparticles were synthesized as nanocarriers to deliver Gab2 siRNA into SKOV3 cells. The silencing effects against the Gab2 gene and the antitumor effects by the chitosan-PEI-Gab2 siRNA nanoparticles (chitosan-PEI-Gab2 NPs) were studied. Results showed that highly efficient silencing effects against Gab2 expression and its downstream effector, AKT protein, at more than 90% deregulation were obtained by chitosan-PEI NP mediated Gab2 siRNA delivery, so as to exhibit obvious antitumor effects against SKOV3 cells with low cytotoxicity, and induce cell apoptosis in early and late stages. The study will provide novel strategies to overcome MBO in ovarian cancer by the efficient knockdown of Gab2 expression.

Effect of platelet-derived growth factor-B on renal cell carcinoma growth and progression.

BACKGROUND: Platelet-derived growth factor-B (PDGF-B) expression promotes the proliferation of mural cells surrounding the blood vessels during angiogenesis. The effect of PDGF-B involved in angiogenesis on tumor growth and progression in clear cell renal cell carcinoma (ccRCC) is unknown. METHODS: We examined the expression of PDGF-B and its receptor PDGFR-ß in 174 patients with ccRCC by microarray analysis. Cancer-specific survival was estimated using the Kaplan-Meier method. PDGF-B-transfected and mock-transfected ACHN cells were implanted into mice to induce tumor formation and tumor growth, respectively, and progression in mice models was assessed using immunohistochemistry and histomorphology. The role of PDGF-B during angiogenesis in vitro was evaluated by flow cytometry analysis, cell migration, and tube formation assay. RESULTS: High expression of PDGF-B was associated with significantly decreased risk of cancer-specific mortality (P ≤ 0.001). The data indicated significant inhibition of tumor growth (P ≤ 0.05) and a reduction in proliferating tumor cells (P = 0.019) in vivo. PDGF-B also inhibits tumor metastasis and invasion events in tumor-bearing mice models. In vitro studies revealed that the tube formation capability of vascular smooth muscle cells (VSMCs), which are believed to be the precursors to pericytes in vivo, significantly induced by PDGF-B. The PDGF-B overexpression also results in a tendency to reside in S and G2/M phases of the cell cycle (P = 0.001) and increasing migration capability of VSMCs (P ≤ 0.001). CONCLUSION: Our results demonstrated that PDGF-B, which increased VSMCs proliferation and migration capability during angiogenesis, limited tumor growth and progression in ccRCC. Therefore, PDGF-B may be a novel and promising prognostic marker.

[Quantitative analysis of alloy steel based on laser induced breakdown spectroscopy with partial least squares method].

In the present paper both the partial least squares (PLS) method and the calibration curve (CC) method are used to quantitatively analyze the laser induced breakdown spectroscopy data obtained from the standard alloy steel samples. Both the major and trace elements were quantitatively analyzed. By comparing the results of two different calibration methods some useful results were obtained: for major elements, the PLS method is better than the CC method in quantitative analysis; more importantly, for the trace elements, the CC method can not give the quantitative results due to the extremely weak characteristic spectral lines, but the PLS method still has a good ability of quantitative analysis. And the regression coefficient of PLS method is compared with the original spectral data with background interference to explain the advantage of the PLS method in the LIBS quantitative analysis. Results proved that the PLS method used in laser induced breakdown spectroscopy is suitable for quantitative analysis of trace elements such as C in the metallurgical industry.

Baicalein ameliorated the upregulation of striatal glutamatergic transmission in the mice model of Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder, which is characterized by a loss of projecting dopaminergic neurons in the substantia nigra and diminished dopamine level in the striatum. Dopaminergic deficit consequently leads to the alterations of striatal basal glutamatergic synaptic transmission and plasticity in the medium spiny neurons. The cytokines and neurotoxins released from the reactive immune cells induced the loss of the projecting dopaminergic neurons in the substantia nigra, which triggering the pathogenesis of PD. The present study investigated the effect of treatment with baicalein (5,6,7-trihydroxyflavone) on the central cytokine synthesis, striatal glutamatergic transmission, and behavioral performance in the rotarod task in the mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Treatment with baicalein significantly attenuated the upregulation of striatal basal glutamatergic strength by decreasing the presynaptic glutamate release and recovering the insertion of postsynaptic glutamate receptor subunit GluR1 induced by MPTP. It also significantly improved the behavioral performance in the rotarod task in the mice injected with MPTP. Treatment with baicalein decreased the upregulation of cytokines (tumor necrosis factor-α and interleukin-1ß) in the substantia nigra and striatum in the mice injected with MPTP. These results indicated that baicalein might serve as novel approach for the treatment of the patients with PD.

Potential study perspectives on mechanisms and correlations between adiposity and malignancy.

Adiposity is a well-recognized risk factor of type 2 diabetes and cardiovascular disease, and recently there is increasing evidence that excess body weight is an avoidable cause of cancer, including gastrointestinal, endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal malignancies. The mechanisms whereby adiposity is associated with tumor development remains not well understood. There are some most studied hypothesized mechanisms such as, high levels of insulin and free levels of insulin-like growth factors, sex hormones, adipocytokines, and inflammatory cytokines, adiposity-induced hypoxia, and so on. The potential mechanisms and conclusions in adiposity associated with increased risk for developing malignancy, and the underlying cellular and molecular mechanisms will be studied very well in the near future.

Expression of CX3CR1 associates with cellular migration, metastasis, and prognosis in human clear cell renal cell carcinoma.

OBJECTIVES: The identification of critical proteins regulating cancer cell metastasis, in clear cell renal cell carcinoma (CCRCC), is important for prediction of prognosis, prevention of metastasis, and treatment of this lethal malignancy. In the present study, we evaluated the role of CX3CR1 in cellular adhesion, migration, and metastasis in CCRCC. We further investigated the downstream molecular signaling mechanism of fractalkine (FKN)-CX3CR1-induced migration and metastasis. MATERIALS AND METHODS: The expression and localization of CX3CR1 in RCC cell lines were assessed by immunofluorescence analysis. The migration of cancer cells was examined by wound healing and transwell migration assay. The expression level of CX3CR1 and FKN in 78 CCRCC individual samples, 16 normal kidney cortex tissue samples, and 16 cases of metastatic lesions of CCRCC were evaluated using immunohistochemical analysis on tissue microarray. The signal pathway of functional FKN was analyzed by the use of the western-blotting method and inhibitory migration assay. RESULTS: CX3CR1 was expressed in human RCC cell lines, and only membrane positive cells were responsible for FKN-induced cell migration. Extracellular signal-related kinases (ERK1/2) and phosphatidyl-inositide 3 kinase/Akt (PI3K/Akt) were each activated upon soluble FKN stimulation in a time-dependent manner, whereas blockades of MEK, PI3K, and G proteins prevented FKN-mediated cellular migration. Furthermore, CCRCC tissue microarray immunohistochemistry data revealed a clear association of strong CX3CR1 expression with tumor metastasis and poor prognosis. CONCLUSIONS: CX3CR1 expression is associated with the process of cellular migration in vitro and tumor metastasis of CCRCC in vivo. Both clinical and molecular cellular evidence suggest that CX3CR1 is a potential marker and therapeutic target for CCRCC prognostic prediction and treatment.

Inhibition of glioma proliferation and migration by magnetic nanoparticle mediated JAM-2 silencing.

Brain invasion is a biological hallmark of glioma that leads to its aggressiveness and prognosis. Junctional adhesion molecule-2 (JAM-2) was found to be overexpressed in human glioma. In this study, the effects of JAM-2 silencing mediated by cell-penetrating magnetic nanoparticles were investigated on glioma cell proliferation and migration in vitro and in vivo. The results showed that the deregulation of JAM-2 in glioma cell lines could cause a dramatic decrease in cell proliferation and migration in vitro. The expression level of cytoskeleton remodeling and migration associated protein genes appeared to be a downstream factor of JAM-2. Furthermore, silencing of JAM-2 expression in implanted glioma cells was found to impair in vivo tumor growth significantly. These data provide new evidence for the role of JAM-2 in the progression of glioma and show its great potential in human glioma gene therapeutics.

[Detection and clinical significance of platelet derived growth factor-BB and microvessel density in clear cell renal cell carcinoma].

OBJECTIVE: To investigate the expression of platelet derived growth factor-BB (PDGF-BB) and microvessel density (MVD) marked with CD34 in clear cell renal cell carcinoma (CCRCC) and explore their relevance to clinicopathologic features and prognoses of patients. METHODS: Expressions of PDGF-BB and CD34 in the tissue samples of 100 clear cell renal cell carcinomas were detected by immunohistochemical (IHC) SP staining. The microvessel density (MVD) was counted using Weidner's method. For PDGF-BB assessment, the staining intensity and the proportion of positive tumor cells were analyzed. Staining was considered immunoreactive when brown granules were identified in the cytoplasm or nuclei of tumor cells. Staining intensity and the proportion of positively stained tumor cells in lesions was scored for further analysis. Statistical analysis was performed using the software SPSS 18.0. RESULTS: The MVD value marked by CD34 in the 100 cancer tissues was (105.49 ± 37.95) profiles/HPF. The median value of MVD in the entire cohort was used as the cut-off point for low MVD group (42 cases) and high MVD group (58 cases). The MVD of the low and high MVD groups was (75.12 ± 22.41) profiles/ HPF and (135.86 ± 22.91) profiles/HPF, respectively, with a statistically significant difference (P < 0.001). MVD was significantly correlated with the tumor T staging, histopathological grading and postoperative metastasis in CCRCC (P < 0.05, respectively). Among the 100 CCRCC cases, there were 38 cases with low PDGF-BB expression and 62 cases with high PDGF-BB expression, and the expression of PDGF-BB was significantly correlated with tumor diameter, T staging, histopathological grading and postoperative metastasis in the CCRCC (P < 0.05, respectively). Kaplan-Meier survival analysis showed that the cancer specific survival (CSS) in CCRCC patients with high expression of MVD and PDGF-BB was significantly better than that in the group with low MVD and low PDGF-BB expression (P < 0.001, respectively). Expression of PDGF-BB protein was positively associated with the MVD assessed by Spearman's correlation and factor analysis (r = 0.461, P < 0.001). CONCLUSION: Significantly increased MVD and PDGF-BB expression detected in CCRCC patients indicate a better tumor grading and staging, and a longer survival time.

[Characteristics of lung function in preterm infants with varying degrees of bronchopulmonary dysplasia].

OBJECTIVE: To explore the characteristics of lung function in preterm infants with varying degrees of bronchopulmonary dysplasia(BPD). METHODS: There were 407 infants (278 males and 129 females) were recruited from Shenzhen Children' Hospital between January 2011 and October 2012.Among them 188 term infants (term group)and 113 preterm infants (non-BPD preterm group) were selected as controls. A total of 106 BPD infants from the observation group were divided into mild(n = 48), moderate (n = 42) and severe(n = 16) sub-groups according to the definition of BPD. Infants with diseases interfering with lung function, such as congenital heart disease, congenital diaphragmatic hernia, or thoracic wall deformities, were excluded. Lung function was tested at a postmenstrual age (PMA) of 44 weeks.q test, Dunnett C test and Spearman analysis were used for statistical analysis. RESULTS: The age range was 17-116 d, test weight range 1.83-7.00 kg and test height range 40.0-64.0 cm.In non-BPD preterm group, the respiratory rate (RR) was higher than that in term group ((50 ± 13) vs (44 ± 10) times/min,P < 0.01) ,while the tidal volume(TV), ratio of time to peak tidal expiratory time and expiratory time (Tpef/Te) and peak expiratory flow(TPEF) were all less than those in term group ((25 ± 9) vs (29 ± 7)ml,29% ± 9% vs 33% ± 8%, (59 ± 23) vs (65 ± 25)ml/s,all P < 0.05) .Neither functional residual capacity(FRC) nor lung clearance index (LCI) had significant statistical difference between two groups ((20 ± 5) vs (19 ± 5)ml/kg, 8.4 ± 2.8 vs 8.7 ± 3.4, all P > 0.05)) . In moderate and severe BPD groups, RR ((57 ± 9), (58 ± 10) times/min) were both higher than that in non-BPD group(both P < 0.05) while RR in mild group ((53 ± 13)times/min)had no statistical significant difference with non-BPD group (P > 0.05). The values of TV and LCI in mild, moderate and severe BPD groups have no statistical significance with non-BPD group (all P > 0.05). Except for mild BPD group(24% ± 13%, (18 ± 5)ml/kg), Tpef/Te and FRC in both moderate and severe groups (20% ± 9% and 18% ± 5%, (15 ± 3)and (15 ± 4)ml/kg)were less than those in non-BPD group(all P < 0.05). Only in severe BPD group ((85 ± 11)ml/s), TPEF was higher than that in non-BPD group(P < 0.05). Correlation analysis showed that, except for LCI, all of these parameters were significantly associated with the degree of BPD(all P < 0.05). CONCLUSIONS: For BPD and non-BPD preterm infants, there are various changes in respiratory rhythm, lung volume, ventilation inhomogeneity, ventilatory efficiency and small airway resistance. The increases of pulmonary elastic recoil and degree of major airway constriction are obvious in moderate and severe BPD infants.

Low differentiated microvascular density and low expression of platelet-derived growth factor-BB (PDGF-BB) predict distant metastasis and poor prognosis in clear cell renal cell carcinoma.

OBJECTIVE: To examine the prognostic significance of the expression of platelet-derived growth factor-BB (PDGF-BB) and differentiated microvascular density (MVD) in patients with clear cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: We used the vascular marker cluster of differentiation 34 (CD34) to identify tumour blood vessels. The expression of PDGF-BB and CD34 was detected by immunohistochemistry (IHC) in tissue microarrays (TMAs) from 100 ccRCCs. Prognostic effects of individual parameters were calculated using Cox regression models and Harrell's concordance index (c-index). RESULTS: Higher grade and more advanced stage ccRCCs had significantly less PDGF-BB expression and differentiated MVD (P < 0.05). Higher PDGF-BB expression was an independent prognostic factor for longer survival, and moreover, the final model built by the addition of PDGF-BB expression improved the predictive accuracy for disease-free survival (c-index 0.707) compared with the clinicopathological-based model (c-index 0.695). PDGF-BB expression was positively associated with differentiated MVD assessed by Spearman correlation and factor analysis (r = 0.634, P < 0.001). CONCLUSION: PDGF-BB is as a novel and promising prognostic marker and antiangiogenic therapeutic target for the treatment of ccRCC.

JAM-2 siRNA intracellular delivery and real-time imaging by proton-sponge coated quantum dots.

In this study, proton-sponge coated quantum dots were prepared by using amphipol PMAL, grafted with polyethylenimine (PEI) as an encapsulation polymer. The QD-PMAL-PEI nanoparticles showed low cytotoxicity and superior gene silencing efficiency in serum-containing medium against junctional adhesion molecule-2 (JAM-2), which is over-expressed in glioma cells. Confocal microscopic analysis showed efficient siRNA intracellular release. In particular, QD-mediated JAM-2 knockdown was reported for the first time to facilitate inhibition of glioma cell migration. Furthermore, the Notch pathway served as the target for the JAM-2 gene function, confirmed by downregulation of its downstream genes HES1 and HES5. The unique proton-sponge coated QDs can serve as multifunctional siRNA carriers for efficient gene silencing and real-time intracellular imaging, and provide a base for design of novel efficient siRNA delivery carriers with high biocompatibility.

Cell-penetrating magnetic nanoparticles for highly efficient delivery and intracellular imaging of siRNA.

RNA interference is one of the most promising technologies for cancer therapeutics, while the development of a safe and effective small interfering RNA (siRNA) delivery system is still challenging. Here, amphipol polymer and protamine peptide were employed to modify magnetic nanoparticles to form cell-penetrating magnetic nanoparticles (CPMNs). The unique CPMN could efficiently deliver the eGFP siRNA intracellularly and silence the eGFP expression in cancer cells, which was verified by fluorescent imaging of cancer cells. Compared with lipofectamine and polyethyleneimine (PEI), CPMNs showed superior silencing efficiency and biocompatibility with minimum siRNA concentration as 5 nm in serum-containing medium. CPMN was proved to be an efficient siRNA delivery system, which will have great potential in applications as a universal transmembrane carrier for intracellular gene delivery and simultaneous MRI imaging.