Construction of SnO2/g-C3N4 an effective nanocomposite for photocatalytic degradation of amoxicillin and pharmaceutical effluent.

The current study mainly focused on the fabrication of 2D graphitic carbon nitride-supported tin oxide nanoparticles (SnO2/g-C3N4) for the effective degradation of Amoxicillin (AMX). Tin oxide (SnO2) NPs were prepared by green and easy modification technique, and then it is decorated over g-C3N4 nanosheets. The structural morphology and surface composition of the synthesized SnO2/g-C3N4 nanocomposite were fully analysed by UV-Vis, XRD, XPS, and HR-SEM with EDAX, FT-IR, and BET analysis. The (HR-TEM) microscopy, the size of SnO2 NPs which as a diameter is about 6.2 nm. The Raman analysis revealed that the SnO2/g-C3N4 composite had a moderate graphitic structure, with a measured ID/Ig value of 0.79. The degradation efficiency of antibiotic pollutant AMX and pharma effluent treatment was monitored by UV spectroscopy. The optical band gap of SnO2 (2.9 eV) and g-C3N4 (2.8 eV) photocatalyst was measured by Tauc plots. To investigate the mechanism through the photodegradation efficiency of the catalyst was analysed by using different Scavenger EDTA-2Na holes (h+) has a greater contribution towards the degradation process. Under visible irradiation, SnO2/g-C3N4 nanocomposite has exhibited an excellent degradation performance of 92.1% against AMX and 90.8% for pharmaceutical effluent in 80 min.

Ceria nanoparticles anchored on graphitic oxide sheets (CeO2-GOS) as an efficient catalyst for degradation of dyes and textile effluents.

Herein, we report a Ceria-graphitic oxide sheets (CeO2-GOS) nanocomposites photo catalyst synthesized by simple and green methods for the degradation of textile effluents and dyes. In the first step, green treated CeO2 NPs were synthesized through a simple organic reduction method. Further, green synthesized CeO2 NPs were anchored with GOS to produce CeO2-GOS nanocomposites by a sol-gel method. The phase morphology and structure of CeO2-GOS nanocomposites was systematically characterized through X-ray diffraction, Raman spectroscopy, zeta potential, Fourier transform infrared spectroscopy (FT-IR), High-Resolution Transmission Electron Microscope (HR-TEM), and X-ray photoelectron spectroscopy (XPS) analysis. Under visible light irradiation, the CeO2-GOS nanocomposites photo catalyst exhibited 83%, 78%, and 70% degradation efficiencies for rhodamine B, methylene blue, and textile effluent, respectively. Due to the synergistic impact of GO, it act as an elastic conductive channel permitting improved charge transport, the fabricated CeO2-GOS nanocomposites showed a significant retort to photo catalysis of rhodamine B, methylene blue, and textile effluent. CeO2-GOS nanocomposites may yield unique insight into the synthesis of green nanocomposites and their application in environmental remediation due to their better photo catalytic activity.

The classification of EEG-based winking signals: a transfer learning and random forest pipeline.

Brain Computer-Interface (BCI) technology plays a considerable role in the control of rehabilitation or peripheral devices for stroke patients. This is particularly due to their inability to control such devices from their inherent physical limitations after such an attack. More often than not, the control of such devices exploits electroencephalogram (EEG) signals. Nonetheless, it is worth noting that the extraction of the features and the classification of the signals is non-trivial for a successful BCI system. The use of Transfer Learning (TL) has been demonstrated to be a powerful tool in the extraction of essential features. However, the employment of such a method towards BCI applications, particularly in regard to EEG signals, are somewhat limited. The present study aims to evaluate the effectiveness of different TL models in extracting features for the classification of wink-based EEG signals. The extracted features are classified by means of fine-tuned Random Forest (RF) classifier. The raw EEG signals are transformed into a scalogram image via Continuous Wavelet Transform (CWT) before it was fed into the TL models, namely InceptionV3, Inception ResNetV2, Xception and MobileNet. The dataset was divided into training, validation, and test datasets, respectively, via a stratified ratio of 60:20:20. The hyperparameters of the RF models were optimised through the grid search approach, in which the five-fold cross-validation technique was adopted. The optimised RF classifier performance was compared with the conventional TL-based CNN classifier performance. It was demonstrated from the study that the best TL model identified is the Inception ResNetV2 along with an optimised RF pipeline, as it was able to yield a classification accuracy of 100% on both the training and validation dataset. Therefore, it could be established from the study that a comparable classification efficacy is attainable via the Inception ResNetV2 with an optimised RF pipeline. It is envisaged that the implementation of the proposed architecture to a BCI system would potentially facilitate post-stroke patients to lead a better life quality.

Green Sources Derived Carbon Dots for Multifaceted Applications.

For the past decade, the Carbon dots (CDs) a tiny sized carbon nanomaterial are typically much attentive due to their outstanding properties. Nature is a fortune of exciting starting materials that provides many inexpensive and renewable resources which have received the topmost attention of researchers because of non-hazardous and eco-friendly nature that can be used to prepare green CDs by top-down and bottom-up synthesis including hydrothermal carbonization, microwave synthesis, and pyrolysis due to its simple synthetic process, speedy reactions and clear-cut end steps. Compared to chemically derived CDs, green CDs are varied by their properties such as less toxicity, high water dispersibility, superior biocompatibility, good photostability, bright fluorescence, and ease of modification. These nanomaterials are a promising material for sensor and biological fields, especially in electrochemical sensing of toxic and trace elements in ecosystems, metal sensing, diagnosis of diseases through bio-sensing, and detection of cancerous cells by in-vitro and in-vivo bio-imaging applications. In this review, the various synthetic routes, fluorescent mechanisms, and applications of CDs from discovery to the present are briefly discussed. Herein, the latest developments on the synthesis of CDs derived from green carbon materials and their promising applications in sensing, catalysis and bio-imaging were summarized. Moreover, some challenging problems, as well as upcoming perspectives of this powerful and tremendous material, are also discussed.

Cyan color-emitting nitrogen-functionalized carbon nanodots (NFCNDs) from Indigofera tinctoria and their catalytic reduction of organic dyes and fluorescent ink applications.

The present study reports the synthesis of nitrogen-functionalized carbon nanodots (NFCNDs) by a low-cost hydrothermal method using the leaf extract of Indigofera tinctoria as a novel carbon precursor. The synthesized NFCNDs were characterized by diverse spectroscopic techniques. The optical properties of N-CNDs were analyzed by UV-visible and fluorescence spectroscopic studies. The quantum yield (QY) for the prepared NFCNDs was found to be 12.6%. The surface morphology, functional groups, and crystallinity of NFCNDs were evaluated by HR-TEM, FT-IR, XRD and Raman spectroscopic methods, respectively. The Raman results revealed the moderate graphite structure of NFCNDs, and the calculated I D/I G value was 0.49. The spherical appearance of the synthesized NFCNDs was confirmed by HR-TEM, and the calculated size of the NFCNDs was 4 nm. The XRD and SAED pattern results gives an evidence for the amorphous nature of the prepared NFCNDs. The thermal stability of NFCNDs was studied by TGA analysis. The resulting NFCNDs acted as a green nanocatalyst and thus efficiently improved the reducing capability of sodium borohydride (NaBH4) in the catalytic reduction of methylene blue (MB) and methyl orange (MO) dyes. Furthermore, the bright cyan emission characteristics of synthesized NFCNDs were utilized as a labeling agent in anti-counterfeiting applications.

Reversal of doxorubicin resistance in lung cancer cells by neferine is explained by nuclear factor erythroid-derived 2-like 2 mediated lung resistance protein down regulation.

Aim: Development of multi drug resistance and dose limiting cardiotoxicity are hindering the use of Doxorubicin (Dox) in clinical settings. Augmented dox efflux induced by lung resistance protein (LRP) over expression has been related to multi drug resistance phenotype in various cancers. An alkaloid from lotus, Neferine (Nef) shows both anticancer and cardioprotective effects. Here, we have investigated the interconnection between nuclear factor erythroid-derived 2-like 2 (NRF2) and LRP in Dox resistance and how Nef can overcome Dox resistance in lung cancer cells by altering this signaling. Methods: Anti-proliferative and apoptotic-inducing effects of Nef and Dox combination in Parental and Dox resistant lung cancer cells were determined in monolayers and 3D spheroids. Intracellular Dox was analyzed using flow cytometry, siRNA knockdown and western blot analysis were used to elucidate NRF2-LRP crosstalk mechanism. Results: We observed that the Dox resistant lung cancer cells expressed higher levels of LRP, reduced glutathione (GSH) and NRF2. Combination of Dox and Nef induced apoptosis, leads to reactive oxygen species (ROS) generation, GSH depletion and reduction in LRP levels contributing to higher intracellular and intranuclear Dox accumulation. The use of N-acetylcysteine and knockdown studies confirmed an important role of ROS and NRF2 in LRP down regulation. Presence of NRF2 binding sites in LRP is support of direct interaction between LRP and NRF2. Conclusion: Nef sensitizes lung cancer cells to Dox by increasing intracellular and/or intra nuclear Dox accumulation via LRP down regulation. This is mediated by redox regulating NRF2. This decoded crosstalk mechanism reinforces the role of NRF2 and LRP in Dox resistance and as an important anticancer target.

Three dimensional in vitro models of cancer: Bioprinting multilineage glioblastoma models.

Three dimensional (3D) bioprinting of multiple cell types within optimised extracellular matrices has the potential to more closely model the 3D environment of human physiology and disease than current alternatives. In this study, we used a multi-nozzle extrusion bioprinter to establish models of glioblastoma made up of cancer and stromal cells printed within matrices comprised of alginate modified with RGDS cell adhesion peptides, hyaluronic acid and collagen-1. Methods were developed using U87MG glioblastoma cells and MM6 monocyte/macrophages, whilst more disease relevant constructs contained glioblastoma stem cells (GSCs), co-printed with glioma associated stromal cells (GASCs) and microglia. Printing parameters were optimised to promote cell-cell interaction, avoiding the 'caging in' of cells due to overly dense cross-linking. Such printing had a negligible effect on cell viability, and cells retained robust metabolic activity and proliferation. Alginate gels allowed the rapid recovery of printed cell protein and RNA, and fluorescent reporters provided analysis of protein kinase activation at the single cell level within printed constructs. GSCs showed more resistance to chemotherapeutic drugs in 3D printed tumour constructs compared to 2D monolayer cultures, reflecting the clinical situation. In summary, a novel 3D bioprinting strategy is developed which allows control over the spatial organisation of tumour constructs for pre-clinical drug sensitivity testing and studies of the tumour microenvironment.

Narrowband Organic Light-Emitting Diodes for Fluorescence Microscopy and Calcium Imaging.

Fluorescence imaging is an indispensable tool in biology, with applications ranging from single-cell to whole-animal studies and with live mapping of neuronal activity currently receiving particular attention. To enable fluorescence imaging at cellular scale in freely moving animals, miniaturized microscopes and lensless imagers are developed that can be implanted in a minimally invasive fashion; but the rigidity, size, and potential toxicity of the involved light sources remain a challenge. Here, narrowband organic light-emitting diodes (OLEDs) are developed and used for fluorescence imaging of live cells and for mapping of neuronal activity in Drosophila melanogaster via genetically encoded Ca2+ indicators. In order to avoid spectral overlap with fluorescence from the sample, distributed Bragg reflectors are integrated onto the OLEDs to block their long-wavelength emission tail, which enables an image contrast comparable to conventional, much bulkier mercury light sources. As OLEDs can be fabricated on mechanically flexible substrates and structured into arrays of cell-sized pixels, this work opens a new pathway for the development of implantable light sources that enable functional imaging and sensing in freely moving animals.

Non-obstructive intracellular nanolasers.

Molecular dyes, plasmonic nanoparticles and colloidal quantum dots are widely used in biomedical optics. Their operation is usually governed by spontaneous processes, which results in broad spectral features and limited signal-to-noise ratio, thus restricting opportunities for spectral multiplexing and sensing. Lasers provide the ultimate spectral definition and background suppression, and their integration with cells has recently been demonstrated. However, laser size and threshold remain problematic. Here, we report on the design, high-throughput fabrication and intracellular integration of semiconductor nanodisk lasers. By exploiting the large optical gain and high refractive index of GaInP/AlGaInP quantum wells, we obtain lasers with volumes 1000-fold smaller than the eukaryotic nucleus (Vlaser < 0.1 µm3), lasing thresholds 500-fold below the pulse energies typically used in two-photon microscopy (Eth ≈ 0.13 pJ), and excellent spectral stability (<50 pm wavelength shift). Multiplexed labeling with these lasers allows cell-tracking through micro-pores, thus providing a powerful tool to study cell migration and cancer invasion.

Matrix metalloproteinase (MMP)-7 in Barrett's esophagus and esophageal adenocarcinoma: expression, metabolism, and functional significance.

Matrix metalloproteinase (MMP)-7, unlike many MMPs, is typically expressed in epithelial cells. It has been linked to epithelial responses to infection, injury, and tissue remodeling including the progression of a number of cancers. We have now examined how MMP-7 expression changes in the progression to esophageal adenocarcinoma (EAC), and have studied mechanisms regulating its expression and its functional significance. Immunohistochemistry revealed that MMP-7 was weakly expressed in normal squamous epithelium adjacent to EAC but was abundant in epithelial cells in both preneoplastic lesions of Barrett's esophagus and EAC particularly at the invasive front. In the stroma, putative myofibroblasts expressing MMP-7 were abundant at the invasive front but were scarce or absent in adjacent tissue. Western blot and ELISA revealed high constitutive secretion of proMMP-7 in an EAC cell line (OE33) that was inhibited by the phosphatidylinositol (PI) 3-kinase inhibitor LY294002 but not by inhibitors of protein kinase C, or MAP kinase activation. There was detectable proMMP-7 in cultured esophageal myofibroblasts but it was undetectable in media. Possible metabolism of MMP-7 by myofibroblasts studied by proteomic analysis indicated degradation via extensive endopeptidase, followed by amino- and carboxpeptidase, cleavages. Myofibroblasts exhibited increased migration and invasion in response to conditioned media from OE33 cells that was reduced by MMP-7 knockdown and immunoneutralization. Thus, MMP-7 expression increases at the invasive front in EAC which may be partly attributable to activation of PI 3-kinase. Secreted MMP-7 may modify the tumor microenvironment by stimulating stromal cell migration and invasion.

Cell cycle dependent expression of the CCK2 receptor by gastrointestinal myofibroblasts: putative role in determining cell migration.

The well-known action of the gastric hormone gastrin in stimulating gastric acid secretion is mediated by activation of cholecystokinin-2 receptors (CCK2R). The latter are expressed by a variety of cell types suggesting that gastrin is implicated in multiple functions. During wound healing in the stomach CCK2R may be expressed by myofibroblasts. We have now characterized CCK2R expression in cultured myofibroblasts. Immunocytochemistry showed that a relatively small proportion (1-6%) of myofibroblasts expressed the receptor regardless of the region of the gut from which they were derived, or whether from cancer or control tissue. Activation of CCK2R by human heptadecapeptide gastrin (hG17) increased intracellular calcium concentrations in a small subset of myofibroblasts indicating the presence of a functional receptor. Unexpectedly, we found over 80% of cells expressing CCK2R were also labeled with 5-ethynyl-2'-deoxyuridine (EdU) which is incorporated into DNA during S-phase of the cell cycle. hG17 did not stimulate EdU incorporation but increased migration of both EdU-labeled and unlabelled myofibroblasts; the migratory response was inhibited by a CCK2R antagonist and by an inhibitor of IGF receptor tyrosine kinase; hG17 also increased IGF-2 transcript abundance. The data suggest myofibroblasts express CCK2R in a restricted period of the cell cycle during S-phase, and that gastrin accelerates migration of these cells; it also stimulates migration of adjacent cells probably through paracrine release of IGF. Together with previous findings, the results raise the prospect that gastrin controls the position of dividing myofibroblasts which may be relevant in wound healing and cancer progression in the gastrointestinal tract.

Network pharmacology of cancer: From understanding of complex interactomes to the design of multi-target specific therapeutics from nature.

Despite massive investments in drug research and development, the significant decline in the number of new drugs approved or translated to clinical use raises the question, whether single targeted drug discovery is the right approach. To combat complex systemic diseases that harbour robust biological networks such as cancer, single target intervention is proved to be ineffective. In such cases, network pharmacology approaches are highly useful, because they differ from conventional drug discovery by addressing the ability of drugs to target numerous proteins or networks involved in a disease. Pleiotropic natural products are one of the promising strategies due to their multi-targeting and due to lower side effects. In this review, we discuss the application of network pharmacology for cancer drug discovery. We provide an overview of the current state of knowledge on network pharmacology, focus on different technical approaches and implications for cancer therapy (e.g. polypharmacology and synthetic lethality), and illustrate the therapeutic potential with selected examples green tea polyphenolics, Eleutherococcus senticosus, Rhodiola rosea, and Schisandra chinensis). Finally, we present future perspectives on their plausible applications for diagnosis and therapy of cancer.

Distinct miRNA profiles in normal and gastric cancer myofibroblasts and significance in Wnt signaling.

Stromal cells influence epithelial function in both health and disease. Myofibroblasts are abundant stromal cells that influence the cellular microenvironment by release of extracellular matrix (ECM) proteins, growth factors, proteases, cytokines, and chemokines. Cancer-associated myofibroblasts (CAMs) differ from adjacent tissue (ATMs) and normal tissue myofibroblasts (NTMs), but the basis of this is incompletely understood. We report now the differential expression of miRNAs in gastric cancer CAMs. MicroRNA arrays identified differences in the miRNA profile in gastric and esophageal NTMs and in CAMs from stomach compared with NTMs. miR-181d was upregulated in gastric CAMs. Analysis of differentially regulated miRNAs indicated an involvement in Wnt signaling. Examination of a microarray data set then identified Wnt5a as the only consistently upregulated Wnt ligand in gastric CAMs. Wnt5a stimulated miR-181d expression, and knockdown of miR-181d inhibited Wnt5a stimulation of CAM proliferation and migration. Analysis of miR-181d targets suggested a role in chemotaxis. Conditioned medium from CAMs stimulated gastric cancer cell (AGS) migration more than that from ATMs, and miR-181d knockdown reduced the effect of CAM-CM on AGS cell migration but had no effect on AGS cell responses to ATM conditioned media. The data suggest that dysregulation of miRNA expression in gastric CAMs, secondary to Wnt5a signaling, accounts at least in part for the effect of CAMs in promoting cancer cell migration.

Release of TGFßig-h3 by gastric myofibroblasts slows tumor growth and is decreased with cancer progression.

Tumor progression has been linked to changes in the stromal environment. Myofibroblasts are stromal cells that are often increased in tumors but their contribution to cancer progression is not well understood. Here, we show that the secretomes of myofibroblasts derived from gastric cancers [cancer-associated myofibroblasts (CAMs)] differ in a functionally significant manner from those derived from adjacent tissue [adjacent tissue myofibroblasts (ATMs)]. CAMs showed increased rates of migration and proliferation compared with ATMs or normal tissue myofibroblasts (NTMs). Moreover, conditioned medium (CM) from CAMs significantly stimulated migration, invasion and proliferation of gastric cancer cells compared with CM from ATMs or NTMs. Proteomic analysis of myofibroblast secretomes revealed decreased abundance of the extracellular matrix (ECM) adaptor protein like transforming growth factor-ß-induced gene-h3 (TGFßig-h3) in CAMs, which was correlated with lymph node involvement and shorter survival. TGFßig-h3 inhibited IGF-II-stimulated migration and proliferation of both cancer cells and myofibroblasts, and suppressed IGF-II activation of p42/44 MAPkinase; TGFßig-h3 knockdown increased IGF-II- and CM-stimulated migration. Furthermore, administration of TGFßig-h3 inhibited myofibroblast-stimulated growth of gastric cancer xenografts. We conclude that stromal cells exert inhibitory as well as stimulatory effects on tumor cells; TGFßig-h3 is a stromal inhibitory factor that is decreased with progression of gastric cancers.

Live birth from vitrified-warmed human oocytes fertilized with frozen-thawed testicular spermatozoa.

A couple with male infertility due to non-obstructive azoospermia were referred to the fertility centre for treatment. Testicular biopsy was performed on the male partner and testicular samples were frozen. The female partner underwent ovarian stimulation and 31 mature oocytes were recovered by ultrasound-guided vaginal aspiration. Twelve oocytes were cryopreserved by the Cryotop vitrification method and 19 oocytes were inseminated by intracytoplasmic sperm injection (ICSI) using frozen-thawed testicular spermatozoa. Nine out of 19 oocytes were fertilized and the resulting embryos were cryopreserved by slow freezing. Four months later, two out of six thawed embryos were transferred, but no pregnancy resulted. One year later, the couple decided to attempt pregnancy using vitrified oocytes and frozen testicular spermatozoa. Six vitrified-warmed oocytes were injected with frozen-thawed testicular spermatozoa and four were fertilized. On the day of transfer, two cleavage stage embryos (4-cell, 2-cell) were obtained. Serum beta-HCG test 14 days after embryo transfer was positive. Hormonal support for the established pregnancy was maintained with oestradiol and progesterone orally until 12 weeks of gestation. A healthy baby boy weighing 3.09 kg was delivered by elective Caesarean section at 38 weeks of gestation. This case report demonstrates that oocyte cryopreservation by the Cryotop vitrification method does not compromise oocyte developmental competence.

In vitro fertilization outcome in severe ovarian hyperstimulation syndrome: An age-matched contemporaneous control study.

Aim: Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening, iatrogenic complication of assisted reproduction and has been associated with poor in vitro fertilization outcome. The aim of the present study was to evaluate the pregnancy rate and outcome following severe OHSS, at a single center over a three-year period. Methods: The incidence of severe OHSS at the IVF Center, National University of Singapore, in Singapore, was 4% (48 cases over 1200 cycles) during the period of 1997-2000. The present retrospective study compared 48 cases of severe OHSS to 144 age-matched, contemporaneous controls without OHSS. Results: The total gonadotropin required for severe OHSS group was found to be lower than for that of controls (2664.06 ± 768.29 IU vs 3349.58 ± 2003.73 IU), although duration of stimulation was similar. The OHSS group was associated with a fivefold increase (OR 5.293, 95% CI: 2.116-13.238) in pregnancy rate compared to controls (87.5% vs 56.9%; P < 0.05). Late OHSS was more common (38/48 cases) and had a pregnancy rate of 97% per embryo transfer. There was no significant difference in the multiple pregnancy (54% vs 48%; P > 0.05) and miscarriage rates (14% vs 7.3%; P > 0.05) between the groups. Conclusion: Severe OHSS at our center were mostly late onset. The pregnancy rate was significantly higher, but multiple pregnancy and miscarriage rates were not significantly increased when compared to the age-matched contemporaneous controls. (Reprod Med Biol 2005; 4: 207-211).

Ovarian hyperstimulation syndrome is associated with reversible impairment of vascular reactivity.

OBJECTIVE: To determine if there is a loss of normal peripheral arteriolar vasoconstrictor reactivity in women with severe ovarian hyperstimulation syndrome (OHSS). SETTING: Prospective controlled study. DESIGN: National University Hospital, Singapore. PATIENT(S): Forty-three women undergoing treatment in an IVF program: 22 women with severe OHSS and 21 normal women without OHSS. INTERVENTION(S): Measurement and quantification of the cutaneous arteriolar vasoconstrictor response using laser Doppler fluximetry. MAIN OUTCOME MEASURE(S): Changes in blood flow as an index of vasoconstrictor response before and after treatment for OHSS with albumin. RESULT(S): The mean (+/-SE) percentage (%) change in normal control women was -68.3% +/- 4.7. This was significantly different from women with OHSS (-32.3% +/- 11.1). The response in women with OHSS changed significantly after treatment with IV albumin (-60.4% +/- 5.7) and was no different than the control response. The reproducibility of the technique was -13.6% (+/-2.8). CONCLUSION(S): Women with OHSS have impaired vascular reactivity when compared with normal women.