Mucins (MUC) protect epithelial barriers from environmental insult to maintain homeostasis. However, their aberrant overexpression and glycosylation in various malignancies facilitate oncogenic ...events from inception to metastasis. Mucin-associated sialyl-Tn (sTn) antigens bind to various receptors present on the dendritic cells (DCs), macrophages, and natural killer (NK) cells, resulting in overall immunosuppression by either receptor masking or inhibition of cytolytic activity. MUC1-mediated interaction of tumor cells with innate immune cells hampers cross-presentation of processed antigens on MHC class I molecules. MUC1 and MUC16 bind siglecs and mask Toll-like receptors (TLRs), respectively, on DCs promoting an immature DC phenotype that in turn reduces T cell effector functions. Mucins, such as MUC1, MUC2, MUC4, and MUC16, interact with or form aggregates with neutrophils, macrophages, and platelets, conferring protection to cancer cells during hematological dissemination and facilitate their spread and colonization to the metastatic sites. On the contrary, poor glycosylation of MUC1 and MUC4 at the tandem repeat region (TR) generates cancer-specific immunodominant epitopes. The presence of MUC16 neo-antigen-specific T cell clones and anti-MUC1 antibodies in cancer patients suggests that mucins can serve as potential targets for developing cancer therapeutics. The present review summarizes the molecular events involved in mucin-mediated immunomodulation, and metastasis, as well as the utility of mucins as targets for cancer immunotherapy and radioimmunotherapy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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•~50 % (w/w) of initial xylan in biomass recovered as XOS in the liquid fraction.•Xylobiose yields of up to 500 g/kg of initial xylan using commercial enzymes.•~75 % conversion of ...initial xylan in biomass to XOS.•Up to 70 % hydrolysis of glucan from residual solids to fermentable glucose.
This study investigated pilot-scale production of xylo-oligosaccharides (XOS) and fermentable sugars from Miscanthus using steam explosion (SE) pretreatment. SE conditions (200 °C; 15 bar; 10 min) led to XOS yields up to 52 % (w/w of initial xylan) in the hydrolysate. Liquid chromatography-mass spectrometry demonstrated that the solubilised XOS contained bound acetyl- and hydroxycinnamate residues, physicochemical properties known for high prebiotic effects and anti-oxidant activity in nutraceutical foods. Enzymatic hydrolysis of XOS-rich hydrolysate with commercial endo-xylanases resulted in xylobiose yields of 380 to 500 g/kg of initial xylan in the biomass after only 4 h, equivalent to ~74 to 90 % conversion of XOS into xylobiose. Fermentable glucose yields from enzymatic hydrolysis of solid residues were 8 to 9-fold higher than for untreated material. In view of an integrated biorefinery, we demonstrate the potential for efficient utilisation of Miscanthus for the production of renewable sources, including biochemicals and biofuels.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Pancreatic fibrosis (PF) is an essential component of the pathobiology of chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC). Activated pancreatic myofibroblasts (PMFs) are crucial ...for the deposition of the extracellular matrix, and fibrotic reaction in response to sustained signaling. Consequently, understanding of the molecular mechanisms of PMF activation is not only critical for understanding CP and PDAC biology but is also a fertile area of research for the development of novel therapeutic strategies for pancreatic pathologies. This review analyzes the key signaling events that drive PMF activation including, initiating signals from transforming growth factor-β1, platelet derived growth factor, as well as other microenvironmental cues, like hypoxia and extracellular matrix rigidity. Further, we discussed the intracellular signal events contributing to PMF activation, and crosstalk with different components of tumor microenvironment. Additionally, association of epidemiologically established risk factors for CP and PDAC, like alcohol intake, tobacco exposure, and metabolic factors with PMF activation, is discussed to comprehend the role of lifestyle factors on pancreatic pathologies. Overall, this analysis provides insight into the biology of PMF activation and highlights salient features of this process, which offer promising therapeutic targets.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary
Grasses represent an abundant and widespread source of lignocellulosic biomass, which has yet to fulfil its potential as a feedstock for biorefining into renewable and sustainable biofuels ...and commodity chemicals. The inherent recalcitrance of lignocellulosic materials to deconstruction is the most crucial limitation for the commercial viability and economic feasibility of biomass biorefining. Over the last decade, the targeted genetic engineering of grasses has become more proficient, enabling rational approaches to modify lignocellulose with the aim of making it more amenable to bioconversion. In this review, we provide an overview of transgenic strategies and targets to tailor grass cell wall polysaccharides for biorefining applications. The bioengineering efforts and opportunities summarized here rely primarily on (A) reprogramming gene regulatory networks responsible for the biosynthesis of lignocellulose, (B) remodelling the chemical structure and substitution patterns of cell wall polysaccharides and (C) expressing lignocellulose degrading and/or modifying enzymes in planta. It is anticipated that outputs from the rational engineering of grass cell wall polysaccharides by such strategies could help in realizing an economically sustainable, grass‐derived lignocellulose processing industry.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
In the present work, 5 wt.% and 10 wt.% yttria-stabilized zirconia (YSZ) nanoparticles were reinforced in Ni-20Cr powder and deposited on boiler tube steel using a high-velocity oxy-fuel spraying ...process. The effect of YSZ reinforcement on microhardness, surface roughness and porosity was investigated. The hardness was the highest for nanocomposite coating reinforced with 10 wt.% YSZ and hardness was found to increase with a decrease in porosity. The coating microstructure and elements were characterized using field emission scanning electron microscopy (FE-SEM) with an energy dispersive spectroscope (EDS). The constituents of the coating were identified using X-ray diffractometer. It was found that the composite coating with 10 wt.% YSZ reinforced nanocomposite coating has the highest microhardness, in the range of 1008-1055 hv. During the coating process, nano YSZ particles were dispersed in the gaps between the micrometric Ni-20Cr particles, providing a better coating matrix than conventional Ni-20Cr. The Ni-20Cr with 10 wt.% of YSZ nanoparticles showed better results in terms of mechanical and microstructural properties during the investigation.
In this research work, nano yttria-stabilized zirconia (YSZ) reinforced Cr3C2-25NiCr composite coatings were prepared and successfully deposited on ASME-SA213-T-22 (T22) boiler tube steel substrates ...using high-velocity oxy-fuel (HVOF) thermal spraying method. Different nanocomposite coatings were developed by reinforcing Cr3C2-25NiCr with 5 and 10 wt.% YSZ nanoparticles. The nanocomposite coatings were analysed by scanning electron microscope (SEM)/Energy-dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD) technique. The porosity of YSZ- Cr3C2-25NiCr nanocomposite coatings was found to be decreasing with the increase in YSZ content, and hardness has been found to be increasing with an increase in the percentage of YSZ in the composite coatings. The coating of 10 wt.% YSZ-Cr3C2-25NiCr showed the lowest porosity, lowest surface roughness, and highest microhardness among all types of coatings. This may be due to the flow of YSZ nanoparticles into the pores and gaps that exist in the base coatings, thus providing a better shield to the substrate material.
One of the challenges to enable targeted modification of lignocellulosic biomass from grasses for improved biofuel and biochemical production lies within our limited understanding of the ...transcriptional control of secondary cell wall biosynthesis. Here, we investigated the role of the maize MYB transcription factor ZmMYB167 in secondary cell wall biosynthesis and how modified ZmMYB167 expression in two distinct grass model species affects plant biomass and growth phenotypes. Heterologous expression of ZmMYB167 in the C
model system Brachypodium led to mild dwarf phenotypes, increased lignin (~7% to 13%) and S-lignin monomer (~11% to 16%) content, elevated concentrations of cell wall-bound p-coumaric acid (~15% to 24%) and reduced biomass sugar release (~20%) compared to controls. Overexpression of ZmMYB167 in the C
model system Zea mays increased lignin (~4% to 13%), p-coumaric acid (~8% to 52%) and ferulic acid (~13% to 38%) content but did not affect plant growth and development nor biomass recalcitrance. Taken together, modifying ZmMYB167 expression represents a target to alter lignin and phenolic content in grasses. The ZmMYB167 expression-induced discrepancies in plant phenotypic and biomass properties between the two grass model systems highlight the challenges and opportunities for MYB transcription factor-based genetic engineering approaches of grass biomass.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Niclosamide (Nic), an FDA-approved anthelmintic drug, is reported to have anti-cancer efficacy and is being assessed in clinical trials for various solid tumors. Based on its ability to target ...multiple signaling pathways, in the present study, we evaluated the therapeutic efficacy of Nic on pancreatic cancer (PC) in vitro. We observed an anti-cancerous effect of this drug as shown by the G0/G1 phase cell cycle arrest, inhibition of PC cell viability, colony formation, and migration. Our results revealed the involvement of mitochondrial stress and mTORC1-dependent autophagy as the predominant players of Nic-induced PC cell death. Significant reduction of Nic-induced reactive oxygen species (ROS) and cell death in the presence of a selective autophagy inhibitor spautin-1 demonstrated autophagy as a major contributor to Nic-mediated cell death. Mechanistically, Nic inhibited the interaction between BCL2 and Beclin-1 that supported the crosstalk of autophagy and apoptosis. Further, Nic treatment resulted in Gsk3β inactivation by phosphorylating its Ser-9 residue leading to upregulation of Sufu and Gli3, thereby negatively impacting hedgehog signaling and cell survival. Nic induced autophagic cell death, and p-Gsk3b mediated Sufu/Gli3 cascade was further confirmed by Gsk3β activator, LY-294002, by rescuing inactivation of Hh signaling upon Nic treatment. These results suggested the involvement of a non-canonical mechanism of Hh signaling, where p-Gsk3β acts as a negative regulator of Hh/Gli1 cascade and a positive regulator of autophagy-mediated cell death. Overall, this study established the therapeutic efficacy of Nic for PC by targeting p-Gsk3β mediated non-canonical Hh signaling and promoting mTORC1-dependent autophagy and cell death.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The main purpose of this study was to fabricate carbon nanotubes (CNTs) reinforced zirconnium yttrium coatings on boiler tube steel and to investigate the microstructural and mechanical properties ...of these coatings. Plasma sprayed conventional ZrO2-Y2O3, ZrO2-Y2O3 and 1 wt.% CNT and ZrO2-Y2O3 and 4 wt.% CNT were prepared and deposited successfully on boiler tube steel material T-91 (ASTM SA-213) by plasma thermal spray technology. Microhardness, porosity, XRD (X-ray diffraction), SEM/EDAX (scanning electron microscopy/energy dispersive X-ray spectroscopy), X-ray mapping and cross-sectional analyses were used to analyse the specimens. The hardness of CNT reinforced ZrO2-Y2O3 increased with the increase in the percentage of CNT, whereas the porosity of the composite coatings decreased with the increase in the CNT percentage. The observed increase in hardness may be attributed to the content of CNT in the composite coating. The present research gives important information related to the fabrication and physical characteristics of CNT-reinforced ZrO2-Y2O3 coatings deposited on T-91 boiler tube steel.
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