Improving Charge Storage of Biaxially-Oriented Polypropylene under Extreme Electric Fields by Excimer UV Irradiation.

Biaxially-oriented polypropylene (BOPP) is one of the most commonly used materials for film-based capacitors for power electronics and pulsed power systems. To address the pressing issue of performance-limiting loss under extreme electric-fields, here a one-step, high-throughput, and environment-friendly process based on very low-dose ultra-violet irradiation from KrCl (222 nm) and Xe2 (172 nm) excimer is demonstrated. The performance of commercial BOPP is boosted in terms of withstanding electric-field extremes (Weibull breakdown strength 694 to 811 V µm-1 by 17% at 25 °C and 428 to 651 V µm-1 by 52% at 120 °C), discharged energy density, and conduction losses. Importantly, the depth profile of space charge is precisely measured in situ with a high resolution of 500 nm by laser induced pressure pulse. Consequently, the space charge effect and electric-field distortion are reduced and related to the improved polymer films. It is demonstrated that energetic UV photons act as scissors for BOPP chains and dissociate oxygen molecules leading to the more thermally stable oxygen-containing structures, as deep traps to impede charge migration. This work provides a promising approach to produce polymers with customized microscopic characteristics that is compatible with the assembly lines of polymer-based capacitors.

Mitotic Dysregulation at Tumor Initiation Creates a Therapeutic Vulnerability to Combination Anti-Mitotic and Pro-Apoptotic Agents for MYCN-Driven Neuroblastoma.

MYCN amplification occurs in approximately 20-30% of neuroblastoma patients and correlates with poor prognosis. The TH-MYCN transgenic mouse model mimics the development of human high-risk neuroblastoma and provides strong evidence for the oncogenic function of MYCN. In this study, we identified mitotic dysregulation as a hallmark of tumor initiation in the pre-cancerous ganglia from TH-MYCN mice that persists through tumor progression. Single-cell quantitative-PCR of coeliac ganglia from 10-day-old TH-MYCN mice revealed overexpression of mitotic genes in a subpopulation of premalignant neuroblasts at a level similar to single cells derived from established tumors. Prophylactic treatment using antimitotic agents barasertib and vincristine significantly delayed the onset of tumor formation, reduced pre-malignant neuroblast hyperplasia, and prolonged survival in TH-MYCN mice. Analysis of human neuroblastoma tumor cohorts showed a strong correlation between dysregulated mitosis and features of MYCN amplification, such as MYC(N) transcriptional activity, poor overall survival, and other clinical predictors of aggressive disease. To explore the therapeutic potential of targeting mitotic dysregulation, we showed that genetic and chemical inhibition of mitosis led to selective cell death in neuroblastoma cell lines with MYCN over-expression. Moreover, combination therapy with antimitotic compounds and BCL2 inhibitors exploited mitotic stress induced by antimitotics and was synergistically toxic to neuroblastoma cell lines. These results collectively suggest that mitotic dysregulation is a key component of tumorigenesis in early neuroblasts, which can be inhibited by the combination of antimitotic compounds and pro-apoptotic compounds in MYCN-driven neuroblastoma.

Macromolecules Absorbed from Influenza Infection-Based Sera Modulate the Cellular Uptake of Polymeric Nanoparticles.

Optimizing the biological identity of nanoparticles (NPs) for efficient tumor uptake remains challenging. The controlled formation of a protein corona on NPs through protein absorption from biofluids could favor a biological identity that enables tumor accumulation. To increase the diversity of proteins absorbed by NPs, sera derived from Influenza A virus (IAV)-infected mice were used to pre-coat NPs formed using a hyperbranched polyester polymer (HBPE-NPs). HBPE-NPs, encapsulating a tracking dye or cancer drug, were treated with sera from days 3-6 of IAV infection (VS3-6), and uptake of HBPE-NPs by breast cancer cells was examined. Cancer cells demonstrated better uptake of HBPE-NPs pre-treated with VS3-6 over polyethylene glycol (PEG)-HBPE-NPs, a standard NP surface modification. The uptake of VS5 pre-treated HBPE-NPs by monocytic cells (THP-1) was decreased over PEG-HBPE-NPs. VS5-treated HBPE-NPs delivered a cancer drug more efficiently and displayed better in vivo distribution over controls, remaining stable even after interacting with endothelial cells. Using a proteomics approach, proteins absorbed from sera-treated HBPE-NPs were identified, such as thrombospondin-1 (TSP-1), that could bind multiple cancer cell receptors. Our findings indicate that serum collected during an immune response to infection is a rich source of macromolecules that are absorbed by NPs and modulate their biological identity, achieving rationally designed uptake by targeted cell types.

Cost-effective screen-printed carbon electrode biosensors for rapid detection of microcystin-LR in surface waters for early warning of harmful algal blooms.

Microcystins (MCs) are toxins produced by cyanobacteria commonly found in harmful algal blooms (HABs). Due to their toxicity to humans and other organisms, the World Health Organization (WHO) sets a guideline of 1 µg L-1 for microcystin-leucine-arginine (MC-LR) in drinking water. However, current analytical techniques for the detection of MC-LR such as liquid chromatography-mass spectrometry (LC-MS) and ELISA are costly, bulky, time-consuming, and mostly conducted in a laboratory, requiring highly trained personnel. An analytical method that can be used in the field for rapid determination is essential. In this study, an anti-MC-LR/MC-LR/cysteamine-coated screen-printed carbon electrode (SPCE) biosensor was newly developed to detect MC-LR, bioelectrochemically, in water. The functionalization of the electrode surface was confirmed with surface characterization methods. The sensor performance was evaluated by electrochemical impedance spectroscopy (EIS), obtaining a linear working range of MC-LR concentrations between 0.1 and 100 µg L-1 with a limit of detection (LOD) of 0.69 ng L-1. Natural water samples experiencing HABs were collected and analyzed using the developed biosensor, demonstrating the excellent performance of the biosensor with a relative standard deviation (RSD) of 0.65%. The interference tests showed minimal error and RSD values against other common MCs and possible coexisting ions found in water. The biosensor showed acceptable functionality with a shelf life of up to 12 weeks. Overall, the anti-MC-LR/MC-LR/cysteamine/SPCE biosensors can be an innovative solution with characteristics that allow for in situ, low-cost, and easy-to-use capabilities which are essential for developing an overarching and integrated "smart" environmental management system.

The role of hepatic Surf4 in lipoprotein metabolism and the development of atherosclerosis in apoE-/- mice.

Elevated plasma levels of low-density lipoprotein-C (LDL-C) increase the risk of atherosclerotic cardiovascular disease. Circulating LDL is derived from very low-density lipoprotein (VLDL) metabolism and cleared by LDL receptor (LDLR). We have previously demonstrated that cargo receptor Surfeit 4 (Surf4) mediates VLDL secretion. Inhibition of hepatic Surf4 impairs VLDL secretion, significantly reduces plasma LDL-C levels, and markedly mitigates the development of atherosclerosis in LDLR knockout (Ldlr-/-) mice. Here, we investigated the role of Surf4 in lipoprotein metabolism and the development of atherosclerosis in another commonly used mouse model of atherosclerosis, apolipoprotein E knockout (apoE-/-) mice. Adeno-associated viral shRNA was used to silence Surf4 expression mainly in the liver of apoE-/- mice. In apoE-/- mice fed a regular chow diet, knockdown of Surf4 expression significantly reduced triglyceride secretion and plasma levels of non-HDL cholesterol and triglycerides without causing hepatic lipid accumulation or liver damage. When Surf4 was knocked down in apoE-/- mice fed the Western-type diet, we observed a significant reduction in plasma levels of non-HDL cholesterol, but not triglycerides. Knockdown of Surf4 did not increase hepatic cholesterol and triglyceride levels or cause liver damage, but significantly diminished atherosclerosis lesions. Therefore, our findings indicate the potential of hepatic Surf4 inhibition as a novel therapeutic strategy to reduce the risk of atherosclerotic cardiovascular disease.

A novel ultrasound-mediated nanodroplet-based gene delivery system for osteoporosis treatment.

This project aimed to develop, optimize, and test an ultrasound-responsive targeted nanodroplet system for the delivery of osteoporosis-related silencing gene Cathepsin K small interfering RNA (CTSK siRNA) for osteoporosis treatment. The nanodroplet (ND) is composed of a gas core made from perfluorocarbon, stabilized with albumin, encapsulated with CTSK siRNA, and embedded with alendronate (AL) for bone targeting (CTSK siRNA-ND-AL). Following the development, the responsiveness of CTSK siRNA-ND-AL to a therapeutic ultrasound probe was examined. The results of biocompatibility tests with human bone marrow-derived mesenchymal stem cells proved no significant cell death (P > 0.05). When the CTSK siRNA-ND-AL was supplemented with human osteoclast precursors, they suppressed osteoclastogenesis. Thus, this project establishes the potential of nanotechnology and ultrasound to deliver genes into the osteoclasts. This research also presents a novel ultrasound responsive and targeted nanodroplet platform that can be used as a gene and drug delivery system for various diseases including cancer.

D4F alleviates the C/EBP homologous protein-mediated apoptosis in glycated high-density lipoprotein-treated macrophages by facilitating autophagy.

The present study aimed to investigate the role of D4F, an apolipoprotein A-I mimetic peptide, in macrophage apoptosis induced by the glycated high-density lipoprotein (gly-HDL)-induced endoplasmic reticulum (ER) stress C/EBP homologous protein (CHOP) pathway, and unravel the regulatory role of autophagy in this process. Our results revealed that except for suppressing the accumulation of lipids within RAW264.7 macrophages caused by gly-HDL, D4F inhibited gly-HDL-induced decrease in the cell viability and increase in lactate dehydrogenase leakage and cell apoptosis, which were similar to 4-phenylbutyric acid (PBA, an ER stress inhibitor). Besides, similar to PBA, D4F inhibited gly-HDL-induced ER stress response activation evaluated through the decreased PERK and eIF2α phosphorylation, together with reduced ATF6 nuclear translocation as well as the downregulation of GRP78 and CHOP. Interestingly, D4F facilitated gly-HDL-triggered activation of autophagy, measured as elevated levels of beclin-1, LC3-II, and ATG5 expressions in macrophages. Furthermore, the inhibition effect of D4F on gly-HDL-induced ER stress-CHOP-induced apoptosis of macrophages was restrained after beclin-1 siRNA and 3-methyladenine (3-MA, an inhibitor of autophagy) treatments, while this effect was further reinforced after rapamycin (Rapa, an inducer of autophagy) treatment. Furthermore, administering D4F or Rapa to T2DM mice upregulated LC3-II and attenuated CHOP expression, cell apoptosis, and atherosclerotic lesions. However, the opposite results were obtained when 3-MA was administered to these mice. These results support that D4F effectively protects macrophages against gly-HDL-induced ER stress-CHOP-mediated apoptosis by promoting autophagy.

Dual Targeting of Chromatin Stability By The Curaxin CBL0137 and Histone Deacetylase Inhibitor Panobinostat Shows Significant Preclinical Efficacy in Neuroblastoma.

PURPOSE: We investigated whether targeting chromatin stability through a combination of the curaxin CBL0137 with the histone deacetylase (HDAC) inhibitor, panobinostat, constitutes an effective multimodal treatment for high-risk neuroblastoma. EXPERIMENTAL DESIGN: The effects of the drug combination on cancer growth were examined in vitro and in animal models of MYCN-amplified neuroblastoma. The molecular mechanisms of action were analyzed by multiple techniques including whole transcriptome profiling, immune deconvolution analysis, immunofluorescence, flow cytometry, pulsed-field gel electrophoresis, assays to assess cell growth and apoptosis, and a range of cell-based reporter systems to examine histone eviction, heterochromatin transcription, and chromatin compaction. RESULTS: The combination of CBL0137 and panobinostat enhanced nucleosome destabilization, induced an IFN response, inhibited DNA damage repair, and synergistically suppressed cancer cell growth. Similar synergistic effects were observed when combining CBL0137 with other HDAC inhibitors. The CBL0137/panobinostat combination significantly delayed cancer progression in xenograft models of poor outcome high-risk neuroblastoma. Complete tumor regression was achieved in the transgenic Th-MYCN neuroblastoma model which was accompanied by induction of a type I IFN and immune response. Tumor transplantation experiments further confirmed that the presence of a competent adaptive immune system component allowed the exploitation of the full potential of the drug combination. CONCLUSIONS: The combination of CBL0137 and panobinostat is effective and well-tolerated in preclinical models of aggressive high-risk neuroblastoma, warranting further preclinical and clinical investigation in other pediatric cancers. On the basis of its potential to boost IFN and immune responses in cancer models, the drug combination holds promising potential for addition to immunotherapies.

Polymeric Nanoparticles with a Sera-Derived Coating for Efficient Cancer Cell Uptake and Killing.

Nanoparticle-mediated cancer drug delivery remains an inefficient process. The protein corona formed on nanoparticles (NPs) controls their biological identity and, if optimized, could enhance cancer cell uptake. In this study, a hyperbranched polyester polymer (HBPE) was synthesized from diethyl malonate and used to generate NPs that were subsequently coated with normal sera (NS) collected from mice. Cellular uptake of NS-treated HBPE-NPs was compared to PEGylated HBPE-NPs and was assessed using MDA-MB-231 triple-negative breast cancer (TNBC) cells as well as endothelial and monocytic cell lines. NS-treated HBPE-NPs were taken up by TNBC cells more efficiently than PEGylated HBPE-NPs, while evasion of monocyte uptake was comparable. NS coatings facilitated cancer cell uptake of HBPE-NPs, even after prior interaction of the particles with an endothelial layer. NS-treated HBPE-NPs were not inherently toxic, did not induce the migration of endothelial cells that could lead to angiogenesis, and could efficiently deliver cytotoxic doses of paclitaxel (taxol) to TNBC cells. These findings suggest that HBPE-NPs may adsorb select sera proteins that improve uptake by cancer cells, and such NPs could be used to advance the discovery of novel factors that improve the bioavailability and tissue distribution of drug-loaded polymeric NPs.

CD30 and ALK combination therapy has high therapeutic potency in RANBP2-ALK-rearranged epithelioid inflammatory myofibroblastic sarcoma.

BACKGROUND: Epithelioid inflammatory myofibroblastic sarcoma (eIMS) is characterised by perinuclear ALK localisation, CD30 expression and early relapse despite crizotinib treatment. We aimed to identify therapies to prevent and/or treat ALK inhibitor resistance. METHODS: Malignant ascites, from an eIMS patient at diagnosis and following multiple relapses, were used to generate matched diagnosis and relapse xenografts. RESULTS: Xenografts were validated by confirmation of RANBP2-ALK rearrangement, perinuclear ALK localisation and CD30 expression. Although brentuximab-vedotin (BV) demonstrated single-agent activity, tumours regrew during BV therapy. BV resistance was associated with reduced CD30 expression and induction of ABCB1. BV resistance was reversed in vitro by tariquidar, but combination BV and tariquidar treatment only briefly slowed xenograft growth compared with BV alone. Combining BV with either crizotinib or ceritinib resulted in marked tumour shrinkage in both xenograft models, and resulted in prolonged tumour-free survival in the diagnosis compared with the relapse xenograft. CONCLUSIONS: CD30 is a therapeutic target in eIMS. BV efficacy is limited by the rapid emergence of resistance. Prolonged survival with combination ALK and CD30-targeted-therapy in the diagnosis model provides the rationale to trial this combination in eIMS patients at diagnosis. This combination could also be considered for other CD30-positive, ALK-rearranged malignancies.

Microplastic accumulation in the gastrointestinal tracts in birds of prey in central Florida, USA.

A study was conducted to quantify the abundance of plastic pollution in the gastrointestinal tracts in birds of prey. Data was collected from all birds retrieved from the Audubon Center for Birds of Prey in central Florida, USA from January to May 2018. Individuals were either dead prior to reaching the Center or died within 24 h of arrival with no food consumed during captivity. Sixty-three individuals representing eight species were dissected to extract the gastrointestinal (GI) tract from the esophagus to the large intestine. Microplastics were found in the GI tracts in all examined species and in all individual birds. The overall mean number (±S.E.) of microplastics for species of bird of prey in central Florida was 11.9 (±2.8), and the overall mean number of microplastics per gram of GI tract tissue was 0.3 (±0.1). A total of 1197 pieces of plastic were recorded. Microfibers accounted for 86% of total plastics followed by microfragments (13%), macroplastics (0.7%) and microbeads (0.3%). Most fibers were either clear or royal blue in color. Micro-Fourier-transform infrared spectroscopy (µ-FTIR) found that processed cellulose was the most common polymer identified in birds (37%), followed by polyethylene terephthalate (16%) and a polymer blend (4:1) of polyamide-6 and poly(ethylene-co-polypropylene) (11%). Two bird species, Buteo lineatus (red-shouldered hawk, n = 28) and Pandion haliaetus (osprey, n = 16), were sufficiently abundant to enable statistical analyses. Microplastics were significantly more abundant per gram in the gastrointestinal tract tissue of B. lineatus, that consumes small mammals, snakes, and amphibians, than in fish-feeding P. haliaetus (ANOVA: p = 0.013). If raptors in terrestrial food webs have higher densities of microplastics than aquatic top predators, then it potentially could be due to a combination of direct intake of plastics and indirect consumption via trophic transfer.

Halomonas montanilacus sp. nov., isolated from hypersaline Lake Pengyanco on the Tibetan Plateau.

A Gram-stain-negative, catalase- and oxidase-positive, aerobic, rod-shaped, motile strain (PYC7WT) was isolated from Lake Pengyanco on the Tibetan Plateau. Comparisons based on 16S rRNA gene sequences showed that strain PYC7WT belongs to the genus Halomonas, with Halomonas malpeensis YU-PRIM-29T and Halomonas johnsoniae T68687T as its closest neighbours (96.8 and 96.6 % 16S rRNA gene sequence similarity, respectively), and only 93.1 % 16S rRNA gene sequence similarity to Halomonas elongata ATCC 33173T. The predominant respiratory quinone of strain PYC7WT is Q-9, with Q-8 as a minor component. The major fatty acids are C18 : 1 ω6c and / or C18 : 1 ω7c, C16 : 0, C16 : 1 ω6c and/or C16 : 1 ω7c, and C12 : 0 3OH. The polar lipids of strain PYC7WT include phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol and two unidentified phospholipids. Genome sequencing revealed a genome size of 4.79 Mbp and a G+C content of 62.9 mol%. DNA-DNA hybridization values of strain PYC7WT showed 45, 30 and 38 % relatedness with Halomonas johnsoniae DSM 21197T, Halomonas hamiltonii DSM 21196T and Halomonas stevensii DSM 21198T, respectively. Combining phenotypic, biochemical, genotypic and DNA-DNA hybridization data, we propose that strain PYC7WT represents a novel species within the genus Halomonas and to have the name Halomonas montanilacus sp. nov.; PYC7WT (=CICC 24506T= KCTC 62529T) is the type strain.

Controlled drug release from polyelectrolyte-drug conjugate nanoparticles.

Encapsulating drugs in functional nanoparticles provides controlled and targeted release of drugs. In this study, a general approach for encapsulating hydrophobic drugs in polyelectrolyte nanoparticles was developed for a controlled drug release. Gemcitabine (GEM), an anticancer drug for pancreatic ductal adenocarcinoma (PDAC), was used as a model drug to produce poly(acrylic acid) (PAA)-GEM conjugate nanoparticles to achieve a controlled release of GEM in cells. The PAA-GEM conjugate nanoparticles were fabricated by coupling GEM onto PAA through the formation of amide bonds. The hydrophobic interactions of GEM molecules induced the formation of the nanoparticles with the GEM core and PAA shell. Fabrication conditions such as the PAA/GEM ratio and pH were optimized to achieve high structure stability and drug loading efficiency. The size and surface charge of the nanoparticles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential measurement. The optimized PAA-GEM nanoparticles had a size around 12 nm, 30 nm and 60 nm in dry state, water, and phosphate buffered saline (PBS), respectively. The encapsulation efficiency was 29.29 ± 1.7%, and the loading capacity was 9.44 ± 0.46%. Less than 7% GEM was released from the PAA-GEM nanoparticles after 96 hour incubation in phosphate buffered saline. The cytotoxic efficacy of the PAA-GEM nanoparticles in cancer cells was investigated through viability studies of PANC-1, a human pancreatic cancer cell line. It was found that the PAA-GEM nanoparticles had more than a 48 hour delay of releasing GEM and had the same cytotoxic efficacy in PANC-1 cells as free GEM. The uptake of the PAA-GEM nanoparticles by PANC-1 cells was investigated using PAA-GEM labeled by rhodamine G6. Fluorescence and bright field overlay images indicated that the PAA-GEM nanoparticles were taken up by PANC-1 cells within 2 hours. It is believed that the PAA-GEM nanoparticles were decomposed in PANC-1 cells and GEM was released from the nanoparticles.

Reverse-D-4F improves endothelial progenitor cell function and attenuates LPS-induced acute lung injury.

BACKGROUND: Patients with acute lung injury (ALI) have increased levels of pro-inflammatory mediators, which impair endothelial progenitor cell (EPC) function. Increasing the number of EPC and alleviating EPC dysfunction induced by pro-inflammatory mediators play important roles in suppressing ALI development. Because the high density lipoprotein reverse-D-4F (Rev-D4F) improves EPC function, we hypothesized that it might repair lipopolysaccharide (LPS)-induced lung damage by improving EPC numbers and function in an LPS-induced ALI mouse model. METHODS: LPS was used to induce ALI in mice, and then the mice received intraperitoneal injections of Rev-D4F. Immunohistochemical staining, flow cytometry, MTT, transwell, and western blotting were used to assess the effect of Rev-D4F on repairment of lung impairment, and improvement of EPC numbers and function, as well as the signaling pathways involved. RESULTS: Rev-D4F inhibits LPS-induced pulmonary edema and decreases plasma levels of the pro-inflammatory mediators TNF-α and ET-1 in ALI mice. Rev-D4F inhibited infiltration of red and white blood cells into the interstitial space, reduced lung injury-induced inflammation, and restored injured pulmonary capillary endothelial cells. In addition, Rev-D4F increased numbers of circulating EPC, stimulated EPC differentiation, and improved EPC function impaired by LPS. Rev-D4F also acted via a PI3-kinase-dependent mechanism to restore levels of phospho-AKT, eNOS, and phospho-eNOS suppressed by LPS. CONCLUSIONS: These findings indicate that Rev-D4F has an important vasculoprotective role in ALI by improving the EPC numbers and functions, and Rev-D4F reverses LPS-induced EPC dysfuncion partially through PI3K/AKT/eNOS signaling pathway.

Halomonas tibetensis sp. nov., isolated from saline lakes on Tibetan Plateau.

Strains pyc13T and ZGT13 were isolated from Lake Pengyan and Lake Zigetang on Tibetan Plateau, respectively. Both strains were Gram-negative, catalase- and oxidase-positive, aerobic, rod-shaped, nonmotile, and nonflagellated bacteria. Phylogenetic analysis based on 16S rRNA gene sequences showed that strains pyc13T and ZGT13 belong to the genus Halomonas, with Halomonas alkalicola 56-L4-10aEnT as their closest neighbor, showing 97.4% 16S rRNA gene sequence similarity. The predominant respiratory quinone of both strains was Q-9, with Q-8 as a minor component. The major fatty acids of both strains were C18:1ω6c/C18:1ω7c, C16:1ω6c/C16:1ω7c, C16:0, and C12:0 3OH. The polar lipids of both strains consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, glycolipid, phospholipids of unknown structure containing glucosamine, and unidentified phospholipids. The DNA G + C content of pyc13T and ZGT13 were 62.6 and 63.4 mol%, respectively. The DNA-DNA hybridization values of strain pyc13T were 34, 41, 61, 35, and 35% with the reference strains H. alkalicola 56-L4-10aEnT, H. sediminicola CPS11T, H. mongoliensis Z-7009T, H. ventosae Al12T, and H. fontilapidosi 5CRT, respectively. Phenotypic, biochemical, genotypic, and DNA-DNA hybridization data showed that strains pyc13T and ZGT13 represent a new species within the genus Halomonas, for which the name H. tibetensis sp. nov. is proposed. The type strain is pyc13T (= CGMCC 1.15949T = KCTC 52660T).

Core-Shell Composite Fibers for High-Performance Flexible Supercapacitor Electrodes.

Core-shell nanofibers containing poly(acrylic acid) (PAA) and manganese oxide nanoparticles as the core and polypyrrole (PPy) as the shell were fabricated through electrospinning the solution of PAA and manganese ions (PAA/Mn2+). The obtained nanofibers were stabilized by Fe3+ through the interaction between Fe3+ ions and carboxylate groups. Subsequent oxidation of Mn2+ by KMnO4 produced uniform manganese dioxide (MnO2) nanoparticles in the fibers. A PPy shell was created on the fibers by immersing the fibers in a pyrrole solution where the Fe3+ ions in the fiber polymerized the pyrrole on the fiber surfaces. In the MnO2@PAA/PPy core-shell composite fibers, MnO2 nanoparticles function as high-capacity materials, while the PPy shell prevents the loss of MnO2 during the charge/discharge process. Such a unique structure makes the composite fibers efficient electrode materials for supercapacitors. The gravimetric specific capacity of the MnO2@PAA/PPy core-shell composite fibers was 564 F/g based on cyclic voltammetry curves at 10 mV/s and 580 F/g based on galvanostatic charge/discharge studies at 5 A/g. The MnO2@PAA/PPy core-shell composite fibers also present stable cycling performance with 100% capacitance retention after 5000 cycles.

G Protein Alpha S Subunit Promotes Cell Proliferation of Renal Cell Carcinoma with Involvement of Protein Kinase A Signaling.

Heterotrimeric G proteins, which are composed of Gα and Gßγ subunits, transduce signals sensed by the coupled surface receptors. Aberrant expressions of G proteins have been observed in many cancer types. This study aimed to determine the expression level of the stimulatory G protein alpha S subunit (Gαs, the main transcript encoded by the GNAS locus) and its biological function in renal cell carcinoma (RCC). Western blotting and quantitative reverse transcription-PCR results show that Gαs expression dramatically increased in RCC cell lines (ACHN, GRC-1, and 786-O) compared to normal renal epithelial cells HK-2. Knockdown of Gαs by small interfering RNA (siRNA) caused a significant inhibition on proliferation of ACHN cells as indicated by MTT assay and colony formation assay. Overexpression of Gαs in HK-2 cells promoted cell proliferation and led to a higher level of intracellular cyclic adenosine monophosphate (cAMP) in response to parathyroid hormone (PTH) compared to the cells transfected with empty vector. Notably, the growth of HK-2 cells overexpressing Gαs was efficiently inhibited in the presence of protein kinase A (PKA) inhibitor H89. Furthermore, in a xenograft model by subcutaneous injection of ACHN cells, tumor growth was also suppressed by H89. Taken together, these results suggest that Gαs plays a tumor-promoting role in RCC and possibly acts through a PKA-dependent pathway. Our findings may provide new clues for target therapy for RCC in the future.

Human autologous mesenchymal stem cells with extracorporeal shock wave therapy for nonunion of long bones.

BACKGROUND: Currently, the available treatments for long bone nonunion (LBN) are removing of focus of infection, bone marrow transplantation as well as Ilizarov methods etc. Due to a high percentage of failures, the treatments are complex and debated. To develop an effective method for the treatment of LBN, we explored the use of human autologous bone mesenchymal stems cells (hBMSCs) along with extracorporeal shock wave therapy (ESWT). MATERIALS AND METHODS: Sixty three patients of LBN were subjected to ESWT treatment and were divided into hBMSCs transplantation group (Group A, 32 cases) and simple ESWT treatment group (Group B, 31 cases). RESULTS: The patients were evaluated for 12 months after treatment. In Group A, 14 patients were healed and 13 showed an improvement, with fracture healing rate 84.4%. In Group B, eight patients were healed and 13 showed an improvement, with fracture healing rate 67.7%. The healing rates of the two groups exhibited a significant difference (P < 0.05). There was no significant difference for the callus formation after 3 months treatment (P > 0.05). However, the callus formation in Group A was significantly higher than that in the Group B after treatment for 6, 9, and 12 months (P < 0.05). CONCLUSION: Autologous bone mesenchymal stems cell transplantation with ESWT can effectively promote the healing of long bone nonunions.

[Analysis of influencing factors on rehabilitation effects for 1 422 preschool deaf children following cochlear implantation].

OBJECTIVE: To investigate the basic factors of the progress amplitude of hearing and speech rehabilitation effect of preschool deaf children with cochlear implants, and provide guidance for the improvement and optimization of rehabilitation strategies. METHOD: Using the standard hearing and language assessment tools, tracked and evaluated 1 422 CI preschool deaf children for a period of one year, and calculated the effect of hearing and speech rehabilitation, carried out the correlation analysis and variance analysis among different grouping variables. RESULT: (1) There was a negative correlation (P<0.01) between the rehabilitation effect and cochlear implantation age, existed the different degree of positive correlation (P<0.01) between the rehabilitation effect and parents cultural level, but no correlation between the rehabilitation effect and parents hearing status.(2) Father's education level, in comparison to mother's education level, had greater impact on the children rehabilitation effect.(3)There was positive correlation(r=0.689, P<0.01) between the progress amplitude of hearing and speech rehabilitation effect. (4) The progress amplitude of auditory and language rehabilitation effect of 2-3 years old group was the highest value(the progress amplitude of hearing and speech recognition rate reached 77.5%, the progress amplitude of language age progress rate reached 2.02 years old), and there were significant differences (P<0.05) between over 3 years old groups. CONCLUSIONS: (1) To expect the better progress amplitude of rehabilitation effect, cochlear implant age should not be more than 3 years old. (2) Father's effect in the process of rehabilitation is more helpful for deaf children's learning enthusiasms.