Background: Tumor microenvironment (TME) plays a crucial role in virtually every aspect of tumorigenesis of glioblastoma multiforme (GBM). The dysfunctional TME promotes drug resistance, disease recurrence and distant metastasis. Recent evidence indicates that exosomes released by stromal cells within TME may promote oncogenic phenotypes via transferring signaling molecules such as cytokines, proteins and microRNAs. Results: In this study, clinical GBM samples were collected and analyzed. We found that GBM-associated macrophages (GAMs) secreted exosomes which were enriched with oncomiR-21. Co-culture of GAMs (and GAM derived exosomes) and GBM cell lines resulted in the increased GBM cells’ resistance against temozolomide (TMZ) by upregulating pro-survival gene, PDCD4 and stemness markers Sox2, STAT3, Nestin and miR-21-5p and increased M2 cytokines, IL-6 and TGF-β1 secreted by GBM cells, promoting the M2 polarization of GAMs. Subsequently, pacritinib treatment suppressed GBM tumorigenesis and stemness; more importantly, pacritinib-treated GBM cells showed markedly reduced ability to secret M2 cytokines and reduced miR-21 enriched exosomes secreted by GAMs. Pacritinib-mediated effects were accompanied by a reduction of oncomiR miR-21-5p, by which tumor suppressor PDCD4 was targeted. We subsequently established a patient-derived xenograft models where mice bore patient GBM and GAMs. The treatment of pacritinib, and the combination of pacritinib/TMZ appeared to significantly reduce tumorigenesis of GBM/GAM PDX mice, overcome TMZ-resistance, and M2 polarization of GAMs. Conclusion: In summation, we showed that potential of pacritinib alone or in combination with TMZ for suppressing GBM tumorigenesis via modulating STAT3/miR-21/PDCD4 signaling. Further investigations are warranted for adopting pacritinib for the treatment of TMZ-resistant GBM in the clinical settings.

The present short communication aimed to determine the effects of vegetable cultivation on health. We conducted a qualitative study using responses to an open-ended question that was part of a survey on regional differences on vegetable intake. Participants in this study were residents of Gunma Prefecture, Japan, and were aged between 20–74 years. In the questionnaire, we asked: “Aside from increasing vegetable intake, how does vegetable cultivation affect your health?” We were able to categorize the answers into six subcategories related to physical health, mental health, and social well-being.

The release profiles of methotrexate, an anticancer drug, from the monoolein liquid crystalline cubic phases were studied. The cubic phases were used either in the form of a lipidic film deposited onto a glassy carbon electrode surface or in the dispersed form of magnetocubosomes, which are considered a prospective hybrid drug delivery system. Commonly, cubosomes or liposomes are employed, but not in the case of toxic methotrexate, known to block receptors responsible for folate transport into the cells. The release profiles of the drug from the lipidic films were monitored electrochemically and described using the Higuchi model. They were also modified via changes in temperature; the release was faster, although deviating from the model when the temperature was increased. Magnetocubosomes - cubic phase nanoparticles containing hydrophobic magnetic nanoparticles placed in an alternating magnetic field of low frequency and amplitude, stimulated drug release from the suspension, which was monitored spectroscopically. These new biocompatible hybrid materials are very promising, allowing to control the release of the drug at the appropriate sites, but do require further investigations into their in vitro cytotoxicity and in vivo biodistribution.

Ammonia-oxidizing microorganism communities are abundant and functionally efficacious in nitrification. However, ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) groups complicate this process in subtropical streams. This study investigates the abundance of ammonia-oxidizing communities south of the Dabie Mountains, China, using quantitative polymerase chain reaction (qPCR). Clone libraries were utilized to analyze the abundance and microbial structures of AOA and AOB in sediments. Such analysis may provide strong evidence reflecting the links within the environment. The results show that AOB had a lower abundance of copies of the ammonia-oxidizing gene (amoA) than AOA. Interestingly, the AOA and AOB community compositions were correlated with ecological characteristics. The dissolved oxygen (DO) and oxidation-reduction potential (ORP) had significant positive correlations, whereas the phosphorus within the structure had a negative correlation with the abundance of both groups. Our study shows that it might adopt some species related to Nitrosotalea clusters that can resist comparably higher pH (toward pH 6.5). Together, these results imply that the physiological adaptation of microbial guilds to environmental pressures in ammonia-oxidizing archaea might allow them to have a more substantial function of ammonia-oxidizing communities in natural habitats.

Now-a-days, the thrust area of materials’ research is to develop multifunctional materials, which have multiple properties in a single functional material. We are interested to develop multifunctional polysilanes having special functional properties such as optical activity and photoluminescence (PL) properties. In this investigation, poly(methyl phenyl silane) (PMPS) was integrated with a chiral unit and a photoactive unit by in situ photopolymerization of (R)-N-(1-phenyl ethyl) methacrylamide (R-NPEMAM) and disperse red 1 methacrylate (DR1MA) monomer in the presence of PMPS. PMPS acted as a macrophotoinitiator and by UV exposure it produced macroradicals which initiated polymerization of chiral and photoactive monomers. Thus a block copolymer of PMPS-b-(R-NPEMAM-ran-DR1MA) was synthesized.The synthesized multifunctional organic inorganic hybrid polymer samples were characterized by FTIR and NMR spectroscopy. The molecular weights of the samples were measured by GPC analysis. The optical, chiroptical and photoluminescence properties were studied. The narrow band at about 1638 cm^-1 is due to C=O stretching vibration of -CONH- of the chiral unit. A wide absorption peaks at 3444 cm^-1 is the characteristic of NH trans stretching vibration of secondary amide group. The asymmetric stretching of NO₂ group appeared at 1481 cm^-1 and the characteristic peak at 1427 cm^-1 was observed due to azo (-N=N-) group stretching of DR1MA unit. The Si-Si band of PMPS appeared at about 462 cm^-1 in FTIR spectra. The optical absorbance observed at 272 nm is due to π-π* transition of aromatic ring and at 330 nm corresponds to σ-σ* transition of Si-Si bond. The other electronic absorption observed in the visible region at 475 nm corresponds to the combined contribution of n-π* and π-π* transition of DR1MA unit. The photoluminescence properties of such polymers were studied for the variation of concentration of the polymer solution and variation with excitation energy such as 275 nm, 325 nm and 475 nm in THF solvent. Such synthesized multifunctional photoactive organic-inorganic polymers having unusual optical, chiroptical and photoluminescence property may find novel optoelectronic (friend foe identification and secretive code identification) applications.

Abstract: The aim of this study is to emphasize on the clinical uses of amniotic membrane (AM) in multiple ocular disorders. AM possesses many properties including promotion of epithelialization, anti-fibrotic, anti-apoptotic, anti-angiogenic properties. Epithelial wound healing on the eye surface is promoted due to several epidermal and keratocyte growth factors as well as by its anti-inflammatory and anti-scarring effects due to interleukin-10, interleukin-1 receptor antagonists and inhibition of transforming growth factor- beta (TGF-β) signal transduction by AM in the corneal and conjunctival fibroblasts respectively. It plays a crucial role by functioning as a substitute of basement membrane (BM) and as a temporary graft material. It is not only being used as an eye graft but also its extract can be used as an eye drop for corneal and external eye diseases. So its proper preparation, preservation and clinical application can bring a revolutionary change in the treatment of different ocular disorders.

Over the past few decades, aircraft Ground Handling Operations (GHO) have been investigated by numerous researchers. Some aspects of GHO have been more focused on than others due to their importance in the GH processes. For instance, GHO performance has been tackled from different perspectives while workers and vehicles allocation suffer from the lack of research in the area. This paper is a literary review of the research that has been conducted in different areas of GHO. It sheds light on GHO performance, resource allocation and scheduling, operations scheduling, vehicle routing, and workers and vehicles allocation.

Abstract: The purpose of this study was to understand the role of infection in the origin of chromosomal anomalies linked to neurodevelopmental disorders. In patients with neurodevelopmental disorders, DNA’s from viruses and bacteria including known teratogens were tested against chromosome anomalies known to cause the disorders. Results support a theory that parental infections disrupt elaborate multi-system gene coordination needed for neurodevelopment. Genes essential for neurons, lymphatic drainage, immunity, circulation, angiogenesis, barriers, structure, and chromatin activity were all found close together in polyfunctional clusters that were deleted in neurodevelopmental disorders. These deletions account for immune, circulatory, and structural deficits that accompany neurologic deficits. In deleted clusters, specific and repetitive human DNA matched infections and passed rigorous artifact tests. In some patients, epigenetic driver mutations were found and may be functionally equivalent to deleting a cluster or changing topologic chromatin interactions because they change access to large chromosome segments. In three families, deleted DNA sequences were associated with intellectual deficits and were not included in any database of genomic variants. These sequences were thousands of bp and unequivocally matched foreign DNAs. Analogous homologies were also found in chromosome anomalies of a recurrent neurodevelopmental disorder. Viral and bacterial DNAs that match repetitive or specific human DNA segments are thus proposed to interfere with highly active break repair during meiosis, and sometimes delete polyfunctional clusters, and disable epigenetic drivers. Mis-repaired gametes produce zygotes containing rare chromosome anomalies which cause neurologic disorders and accompanying non-neurologic signs. Neurodevelopmental disorders may be examples of assault on the human genome by foreign DNA with some infections more likely tolerated because they resemble human DNA segments. Further tests of this model await new technology.

Children with central nervous system (CNS) malignancies often suffer from high symptom burden and risk of death. Pediatric palliative care is a medical specialty, provided by an interdisciplinary team, which focuses on enhancing quality of life and minimizing suffering for children with life-threatening or life-limiting disease, and their families. Primary palliative care skills which include basic symptom management, facilitation of goals-of-care discussions, and transition to hospice can and should be developed by all providers of neuro-oncology care. This chapter will review the fundamentals of providing primary palliative care

Abstract: The contribution of breakfast to diet quality (DQ) can inform future dietary guidelines. This study examined breakfasts that were associated with highest-quality diets. Dietary data came from the first reported day of the National Health and Examination Survey (NHANES) 2011-2014 (n=14,488). DQ measures were the Nutrient Rich Foods Index (NRF9.3) and the USDA Healthy Eating Index 2015 (HEI 2015). Analyses of breakfast intakes were conducted by NRF9.3 tertiles and by age and socioeconomic groups. Four out of 5 NHANES participants ate breakfast. Breakfast provided 19-22% of dietary energy depending on age. Breakfast intakes of complex carbohydrates and total sugars were higher and intakes of protein and fats were lower relative to energy intakes. Breakfast provided more that 20% of daily intakes of B vitamins, vitamins A and D, folate, calcium, iron, potassium and magnesium. Eating breakfast was associated with higher NRF9.3d scores. Breakfasts associated with top tertile of NRF9.3d had more carbohydrates and less added sugars and fats. Such breakfasts had more fruit and juices, more whole grains, more milk and yogurt and less meat and eggs. Breakfast patterns that favored fruit, whole grains, and dairy were associated with healthiest diets.

Abstract: We have filled a 24 mm diameter glass sphere with a transparent polymer-gel that is radio-fluorogenic, i.e. it becomes (permanently) fluorescent when irradiated, with an intensity proportional to the local dose deposited. The gel consists of >99.9% tertiary-butyl acrylate (TBA) pre-polymerized to ~15% conversion, and ~100 ppm maleimido-pyrene (MPy). Its dimensions and physical properties are close to those of the vitreous body of the human eye. We have irradiated the gel with a 3 mm diameter, 200 kVp X-ray beam with a dose rate of ~1 Gy/min. A 3D (video) view of the beam within the gel has been constructed from tomographic images obtained by scanning the sample through a thin sheet of UV light. To minimize optical artifacts, the cell was immersed in a square tank containing a refractive-index-matching medium. The 20%-80% penumbra of the beam was determined to be ~0.4 mm. The research was a preparatory investigation of the possibility of using the method to monitor the millimetre diameter proton pencil beams used in ocular radiotherapy.

To investigate whether the ech42 gene in Clonostachys rosea can improve the biocontrol efficacy of Bacillus amyloliquefaciens and its molecular mechanism.Compared to the wild type, the B. amyloliquefaciens transformed with the ech42 gene exhibited a higher chitinase activity. The B. amyloliquefaciens-ech42 also showed a significantly higher biocontrol efficiency against B. cinerea when tomato plants were pre-treated with amyloliquefaciens-ech42. No significant difference of control efficiency was observed between the wild type and amyloliquefaciens-ech42 when tomato plants were first infected by B. cinerea. In addition, the activity of the defense-related enzyme polyphenol oxidase, but not superoxide dismutase was significantly higher in amyloliquefaciens-ech42 than in the wild type.The ech42 enhances the Bacillus amyloliquefaciens biocontrol efficiency by increasing the capacity of protection/prevention to plants, rather treating/killing the pathogens.

Abstract: We review the development and application of an organic polymer-gel capable of producing fixed, three-dimensional fluorescent images of complex radiation fields. The gel consists for more than 99% of γ-ray-polymerized (~15% conversion) tertiary-butyl acrylate (TBA) containing ~100 ppm of a fluorogenic compound, e.g. maleimido-pyrene (MPy). The radio-fluorogenic effect depends on copolymerization of the MPy into growing chains of TBA on radiation-induced polymerization. This converts the maleimido residue, which quenches the pyrene fluorescence, into a succinimido moeity (SPy), which doesn't. The intensity of the fluorescence is proportional to the yield of free-radicals formed and hence to the local dose deposited. Because the SPy moieties are built into the cross-linked polymer matrix the image is fixed. The method of preparing the gel and imaging the radiation-induced fluorescence are presented and discussed. The effect is illustrated with fluorescent images of the energy deposited in the gel by beams of X-rays, electrons and protons as well as a radioactive isotope.

A B S T R A C T Genital herpes disease is caused mainly by herpes simplex virus type 2 (HSV-2), which is sexually transmitted with a high prevalence in both developed and developing countries. No vaccine is currently available against genital herpes. In this study, we introduced and expressed two genes encoding HSV-2 glycoprotein D (gD) and VP16 protein and a GFP marker gene (control) in tobacco seedlings. Positive plant infection was assessed through characteristic tobacco mosaic virus disease symptoms on leaves and by monitoring the fluorescence emitted by the expressed GFP protein. Expression of the HSV-gD2 and VP16 antigens was verified by RT-PCR, ELISA and Western blot. As a proof of concept, the immunogenicity and the protection ability of the plant produced gD antigen was tested in a mouse model of genital herpes and compared to gD antigen produced in a mammalian expression system. This showed that the plant-gD preparation, when used in combination with a CpG oligodeoxynucleotide as adjuvant, was highly immunogenic and capable of inducing complete immunity to lethal vaginal HSV-2 challenge in mice. Thus, the data presented here may have implications for the development of a production system for highly immunogenic plant-based HSV-2 vaccine antigens.

Abstract Antibacterial activities can be improved using mixed ligands. Mixed ligands involved in this research are sodium sulfadiazine (Na-sfz) and dithiocarbamate (ai-dtc). One-pot synthesis was used to synthesize ligand of aniline dithiocarbamate (ai-dtc) and the corresponding coordination compounds of [VO(sfz)(ai-dtc)] and [Zn(sfz)(ai-dtc)]. Crystals of ai-dtc, which grew from the solution when refrigerated after five days, were diffracted with technique of single crystal x-ray crystallography to reveal the structure. Other characterization techniques involving physicochemical parameters, FT-IR, UV-Vis and NMR (1H NMR and 13C NMR) were carried out on ligands of ai-dtc, sfz and corresponding coordination compounds. Differences in results of FT-IR, UV-Vis and NMR between ligands and their respective metal ions confirmed the coordination. The in vitro antibacterial studies showed that the ligands (not the metal complexes) had modest activity against Gram negative bacteria: Staphylococcus aureus, whereas, the coordination compounds had modest activities against the Gram negative bacteria: Escherichia coli and Pseudomonas aeruginosa.

Abstract: The study focuses on how socio-economic and demographic indicators affect fertilization sustainability (excessive amount of fertilization). Principally we aim to examine the significance magnitude of the effects of three socio-demographic variables such as traditional way of fertilization, rental land farming, and farmers’ younger age on over-fertilization in Bangladesh and other developing countries. In 1960s, Bangladesh state authority launched a campaign ‘Grow more Food’ to feed huge numbers of population and thus the farmers are provided chemical fertilizers and pesticides at a subsidized low price. Farmers began to use huge amount of fertilizers for gaining high yields and continued it to present causing environmental woes a lot. We interview (face-to-face, focus group discussion, and phone interview) 210 Bangladesh farmers in 2016 by semi-structured questionnaire. Data has been analyzed using General Linear Model (GLM) in Univariate Analysis of Variance. The study found the effect of traditional way of fertilization on excessive amount of fertilization is strongly significant at 1% level. Apart from, rental land farming and farmers’ younger age have a significant influence on over- fertilization; though their significance level (5% and 10% respectively) is quasi-strong. Policy makers can be able to formulate fertilizer policy on the basis of these findings.

Background: Diabetic retinopathy (DR) is one of the most prominent pathological microvascular complications in diabetes. A series of studies reported that vitamin D deficiency was associated with increased prevalence of retinopathy in diabetic patients but the results were inconsistent. In this study we focused on evaluating the relationship between vitamin D deficiency and DR by conducting a meta-analysis of observational studies. Methods: Systematic computerized searches were performed in PubMed, MEDLINE, and the Cochrane Library for relevant original articles till November 20, 2016. The pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated to assess the associated value of vitamin D deficiency to the risk of DR. 9 studies including 6332 participants were subjected to final analysis. Results: The results indicated that vitamin D deficiency increases the risk of DR (OR = 1.57, 95% CI 1.32-1.87) with a little heterogeneity (I2 = 23%). In addition, the subgroup analysis demonstrated that there were obvious heterogeneities in T2DM (I2 = 47.8%). Sensitivity analysis showed that the results were relatively stable and reliable. Conclusion: our meta-analysis demonstrated that vitamin D deficiency could increase the risk of DR.

The paper presents the findings of research on companies in the early stage of development based on the concept of ensuring their sustainability. The starting point is attributes shaping a sustainable model of start-ups. A solution has been proposed and examined that identifies the factors dynamising a business model, which give the company the ability to make fast changes in the configuration of the business model, and that applies stabilizing factors based on the concept of the Triple Bottom Line. The research problem is a response to the phenomena of the bankruptcy of many start-ups that cannot find a way to survive in the long term. The business models of companies in the early stage of development should be designed taking into account the possibility of their dynamic and iterative changes when the earlier assumptions do not work when implemented in practice. A cognitive gap has been observed as the relevant literature does not propose a systemic solution to the problem of instability of the startups viewed from the perspective of the business model concept. The research problem, therefore, is to identify potential new methods to ensure the sustainability of young companies trying to combine aspects dynamising changes in business models, taking into account economic, environmental and social aspects. The findings of research on companies in the early stage of development show that when the methods of increasing the flexibility of the business model are applied and attention is drawn to environmental and social activities and a strong emphasis is put on financial performance, reflecting the expectations of shareholders, the concept of ensuring the sustainability of young companies from the point of view of sustainable business model attributes emerges.