Energy Harvesting Using ZnO Nanosheet-Decorated 3D-Printed Fabrics.

In this work, we decorated piezoresponsive atomically thin ZnO nanosheets on a polymer surface using additive manufacturing (three-dimensional (3D) printing) technology to demonstrate electrical-mechanical coupling phenomena. The output voltage response of the 3D-printed architecture was regulated by varying the external mechanical pressures. Additionally, we have shown energy generation by placing the 3D-printed fabric on the padded shoulder strap of a bag with a load ranging from ∼5 to ∼75 N, taking advantage of the excellent mechanical strength and flexibility of the coated 3D-printed architecture. The ZnO coating layer forms a stable interface between ZnO nanosheets and the fabric, as confirmed by combining density functional theory (DFT) and electrical measurements. This effectively improves the output performance of the 3D-printed fabric by enhancing the charge transfer at the interface. Therefore, the present work can be used to build a new infrastructure for next-generation energy harvesters capable of carrying out several structural and functional responsibilities.

In Situ Study of Structure Formation under Stress in Stretchable Conducting Nanocomposites.

One of the major limitations of flexible sensors is the loss of conductivity upon multiple stretching and bending cycles. Conducting fillers with two different geometries, carbon black and carbon nanotubes, were introduced in polydimethylsiloxane (PDMS) for physical insights into the structure formation of nanofillers by the application of periodic tensile stress. The loading of the nanofillers was selected beyond the percolation threshold to determine the cyclic stability of the resulting network channels. The surface chemistry of carbon nanotubes has been varied to understand the interfacial interactions at the molecular length scale. The combination of in situ stretching, annealing, and vis-à-vis conductometry of nanocomposite films with synchrotron-based ultra-small angle X-ray scattering experiments enables us to highlight the importance of the fractal dimensions of nanofillers for the molecular level interactions. The irreversible formation of nanofiller network geometries under cyclic stress and annealing was found to be responsible for the electrical properties of a flexible conducting film.

Construction and stable gene expression of AGR2xPD1 bi-specific antibody that enhances attachment between T-Cells and lung tumor cells, suppress tumor cell migration and promoting CD8 expression in cytotoxic T-cells.

There has been a substantial and consistent rise in the number of clinical trials to develop advanced and potent bispecific antibodies (BsAb) over the past two decades with multiple targets to improve the efficacy or tissue specificity of monoclonal antibodies (mAb) treatment for diseases with multiple determining factors or widely-expressed targets. In this study, we designed and synthesized BsAb AGR2xPD1 targeting extracellular AGR2, a paracrine signal, and PD1, an immune checkpoint protein. Our design is intended to use AGR2 binding to guide PD1 targeting for AGR2+cancer. We used this construction to produce AGR2xPD1 BsAb by generating clonally selected stable 293F cell line with high expression. Applying this BsAb in a T cell-Tumor cell co-culture system showed that targeting both PD1 and AGR2 with this BsAb induces the attachment of TALL-104 (CD8+ T-lymphocytes) cells onto co-cultured H460 AGR2+ Lung tumor cells and significantly reduces migration of H460 cells. T-cell expression of CD8 and IFNγ is also synergistically enhanced by the AGR2xPD1 BsAb treatment in the AGR2+H460 co-culture system. These effects are significantly reduced with AGR2 expression negative WI38 cells. Our results demonstrate that the AGR2xPD1 BsAb could be a potential therapeutic agent to provide better solid tumor targeting and synergetic efficacy for treating AGR2+ cancer by blocking AGR2 paracrine signaling to reduce tumor survival, and redirecting cytotoxic T-cells into AGR2+ cancer cells.

Coherent Loading-Deloading Mechanism in Polymeric Nanohybrid Network Structures.

Physically cross-linked gels have unique advantages of repeated swelling and shrinking of network structures, where the stability of gels at the swelled phase, particularly under ionic conditions, is extremely critical. In this study, it has been shown that functionalized nanofillers and polar solvents can increase the network densities of physically cross-linked gels with higher dimensional stability by increasing the polar and electrostatic interactions. The characteristic nonbonded interactions of CNTs with ionic solvents have been utilized for the controlled swelling of toughened double-network gels as the function of pH and time. The swelling of the overall gel morphology is found to be important for the release of analytes; however, the functional cross-sectional sites in the nanohybrids hold the key for desorption kinetics. The selection of interactive functional moieties in the nanohybrids and analytes has led to the development of highly efficient and controlled release media. The electrostatic interaction of analytes with functionally and dimensionally stable gels with controlled porosity indicates a clear structure-property correlation, which could be exploited to design and fabricate efficient drug delivery vehicles and rapid surface decontaminants.

Methyl Methacrylate-Based Copolymers: Recent Developments in the Areas of Transparent and Stretchable Active Matrices.

The recent advancements of poly(methyl methacrylate) (PMMA) as a transparent flexible polymer material have been utilized in numerous areas of engineering and materials science. PMMA-based copolymers demonstrate outstanding mechanical and optical properties owing to high transparency, lightweight nature, high impact resistance, and stress relaxation across glass transition temperature. These copolymers have unique characteristics of retaining optical and microstructural integrities during successive bending or elongations which make them an attractive choice for materials of stretchable electronics. In particular, there has been an escalated rise in the use of methyl methacrylate (MMA)-based transparent and stretchable copolymer films during the recent decades. Therefore, we have highlighted these recent developments into a comprehensive review in order to aid the future progress in these diverse fields. Herein, we have highlighted the scope of MMA as an important building block for the synthesis of highly transparent and flexible materials. The synthetic pathways of these copolymer materials and the resulting mechanical properties have been discussed. Moreover, the immense scope of these copolymer films has been highlighted by virtue of their applications in various industries.

CoFe2O4 Nanoparticles Grown within Porous Al2O3 and Immobilized on Graphene Nanosheets: A Hierarchical Nanocomposite for Broadband Microwave Absorption.

Demands to develop efficient microwave-absorbing materials are increasing with the advancement of information technology and the exponential rise in the usage of electromagnetic devices. To reduce electromagnetic interference and to overcome the adverse effects caused by microwave exposure resulting from the excessive usage of electromagnetic devices, microwave absorbers are very necessary. In addition, radar-absorbing materials are essential for stealth technology in military applications. Herein, we report a nanocomposite in which CoFe2O4 (CF) nanoparticles were grown within the porous structure of Al2O3 (PA), and this CoFe2O4-loaded Al2O3 (PA-CF) nanocomposite was immobilized on the surface of nanometer-thin graphene sheets (Gr). Owing to the hierarchical structure created by the constituents, the (60PA-40CF)90-Gr10 nanocomposite exhibited excellent microwave-absorption properties in the X-band region with a reflection loss (RL) value of ∼-30.68 dB (∼99.9% absorption) at 10.71 and 9.04 GHz when thicknesses were 2.0 and 2.3 mm, respectively. This nanocomposite demonstrated its competence as a lightweight, high-performance microwave absorber in the X-band region, which can be utilized in the applications of pioneering stealth technology.

A high efficient FVIII variant corrects bleeding in hemophilia A mouse model.

Hemophilia A is a bleeding disorder caused by quantitative or qualitative deficiencies in coagulation factor VIII (FVIII). Low FVIII expression due to its unstable mRNA and binding with immunoglobulin-binding protein (BiP) compromises gene therapy endeavors in hemophilia A. Site-directed mutagenesis have demonstrated an improvement in the expression of FVIII proteins. In this study, a targeted point mutation of Pro at position 290 to Thr (P290T) enhances the in vitro specific activity of B-domain-deleted factor VIII (BDD-FVIII). Hydrodynamic gene delivery of P290T cDNA into FVIII-deficient (FVIII-/-) mice corrected bleeding symptoms. P290T variant resulted in high plasma FVIII coagulant activity 24 h post-gene delivery. Furthermore, bleeding time and average blood loss was significantly reduced in FVIII-/- mice injected with P290T variant, whereas BDD-FVIII and PBS-injected mice experienced prolonged bleeding and excessive blood loss. Histological analysis of the liver biopsies revealed no apparent signs of liver damage. No signs of potential toxicity were seen in mice following mice bodyweights assessment. Altogether, our results demonstrate that the introduction of P290T mutation increases both in vitro and in vivo FVIII coagulant activity, supporting ongoing efforts to develop more effective replacement therapy for hemophilia A.

Dual-Purpose CuFe2O4-rGO-Based Nanocomposite for Asymmetric Flexible Supercapacitors and Catalytic Reduction of Nitroaromatic Derivatives.

Energy storage and environmental pollution are two major global concerns in today's scenario. As a result of the momentous exhaustion of fossil fuels, the generation of energy from renewable sources is gaining immense importance. However, the irregular availability of energy from these renewable sources is the major encounter to achieve sustainable energy harvesting technology, yielding efficient but continuous and reliable energy supplies. Apart from the requirement of state-of-the-art heavy-duty technologies such as transportation, defense, etc., in the modern lifestyle to fulfill the demand for flexible electronic devices, the development of high-performance mechanically flexible all-solid-state supercapacitors is increasing massively. On the other hand, to cater to the need for accessibility of clean water for healthy lives, several technologies are evolving to treat wastewater and groundwater. Hence, the development of efficient catalysts for destroying water pollutants is an attractive approach. Considering these two crucial facets, in this paper, we have demonstrated the multifunctional features of a CuFe2O4-rGO nanocomposite, which was exploited to fabricate a high-performance mechanically flexible all-solid-state asymmetric supercapacitor and simultaneously used as an efficient but easily recoverable catalyst for the transformation of different nitroaromatic compounds. We have also demonstrated the conversion of trifluralin (a herbicide), which is present in the water body as a pollutant, to its corresponding amine derivatives, which can be utilized in the preparation of important pharmaceutical products.

Extracellular AGR2 activates neighboring fibroblasts through endocytosis and direct binding to ß-catenin that requires AGR2 dimerization and adhesion domains.

Anterior gradient 2 (AGR2) is often overexpressed in several types of cancer. AGR2 is cytoplasmic or secreted as an extracellular signal. Intracellular AGR2 properties and role in cancer have been well studied, but its extracellular function is largely unclear. It has been shown that extracellular AGR2 activates endothelial cells and fibroblasts in culture, but the mechanism of AGR2 signaling is not well elucidated. Here, we report that tumor secreted or externally added AGR2 translocates into cytoplasm by endocytosis, binds to ß-catenin and further co-translocates to the nucleus in NIH3T3 fibroblasts. Externally added AGR2 also increased ß-catenin expression, stability, and accumulation in the nucleus in both fibroblasts and cancer cells. External AGR2 rescued the expression of ß-catenin, which was suppressed by EGFR inhibitor AG1478 indicating an alternative pathway to regulate ß-catenin independent of EGFR signal. These effects were abolished when a monoclonal antibody against AGR2 was added to the experiments, confirming the effects are caused by AGR2 only. Putting together, our results show that extracellular AGR2 signaling pathway involves endocytosis mediated cellular translocation, direct binding and regulating ß-catenin nuclear accumulation. It is also a target against tumor initiated AGR2 signaling to form and maintain tumor microenvironment.

A novel target anti-interleukin-13 receptor subunit alpha-2 monoclonal antibody inhibits tumor growth and metastasis in lung cancer.

IL13Rα2 shows high expression in different types of tumors and can be a target for cancer therapy in humans due to its poor prognosis. The aim of our study is to characterize and investigate the effect of interleukin-13 receptor subunit alpha-2monoclonal antibody mAb15D8 on lung cancer cells in vitro and in vivo by blocking its specific epitope in IL13Rα2 antigen. The mAb15D8 blocking epitope was analyzed through the mutagenesis of IL13Rα2 and confirmed with western blot. We found that the IL13Rα2 epitope recognized by mAb15D8 antibody is a new binding site localized in the fibronectin-III domain-1 of IL13Rα2 antigen. Moreover, the mAb15D8 obviously reduced cell proliferation, migration of H460, A549, SKOV3, and B16F10 cells. Treatment with mAb15D8 significantly reduced the H460 xenograft tumor formation and growth in nude mice and inhibited B16F10 tumor metastasis and increased survival in C57BL/6 mice. Pharmacokinetic and toxicological analysis demonstrated the safety of mAb15D8 as a potential therapeutic agent. We developed a novel mouse monoclonal antibody against IL13Rα2 which binds to specific epitope on IL13Rα2 antigen. In vivo treatment with the antibody significantly reduced tumor growth and lung metastasis and prolonged survival. These results suggest mAb15D8 antibody as a potential therapeutic agent for cancer therapy.

Understanding fluorometric interactions in ion-responsive sustainable polymer nanocomposite scaffolds.

The fluorescent colour in biodegradable and biocompatible flexible polymer nanocomposite gels was modulated in order to gain insight into the interfacial interactions of functional scaffolds with metal ions. The hybrid nanomaterials were introduced into the polymer matrix to obtain mechanically robust porous morphologies where the intrinsic luminescence matrix was found to critically enhance the threshold of the visual detection limits. The quenching of fluorescence intensity has been predominantly attributed to the interactions of functional receptors of luminescent nanofillers with respect to the chromophores of the fluorescent matrix. The chromium ion is selected to understand the change in fluorescence intensity of the nanocomposite gel with the degree of metal ion adsorption. The number of functional nanomaterials loaded into the matrix and the luminescence nature of the base polymer are varied with the purpose of gaining insight into the remote sensing mechanism of the colorimetric fluorescent probe.

Withdrawal Notice: Emerging Novel Coronavirus is a Global Threat: Insight in the Biology of COVID-19 and its Hijacking Process of Hosts' Cell

The article has been withdrawn by the editorial office of the journal Current Pharmaceutical Design, due to major linguistic inconsistencies.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Organic anion transporter 1 and 3 contribute to traditional Chinese medicine-induced nephrotoxicity.

With the internationally growing popularity of traditional Chinese medicine (TCM), TCM-induced nephropathy has attracted public attention. Minimizing this toxicity is an important issue for future research. Typical nephrotoxic TCM drugs such as Aristolochic acid, Tripterygium wilfordii Hook. f, Rheum officinale Baill, and cinnabar mainly damage renal proximal tubules or cause interstitial nephritis. Transporters in renal proximal tubule are believed to be critical in the disposition of xenobiotics. In this review, we provide information on the alteration of renal transporters by nephrotoxic TCMs, which may be helpful for understanding the nephrotoxic mechanism of TCMs and reducing adverse effects. Studies have proven that when administering nephrotoxic TCMs, the expression or function of renal transporters is altered, especially organic anion transporter 1 and 3. The alteration of these transporters may enhance the accumulation of toxic drugs or the dysfunction of endogenous toxins and subsequently sensitize the kidney to injury. Transporters-related drug combination and clinical biomarkers supervision to avoid the risk of future toxicity are proposed.

Microphase separation in oriented polymeric chains at the surface of nanomaterials during nanofiber formation.

The presence of low-dimensional functional nanofillers during the formation of morphological phase boundaries in polymeric nanofibers by electrospinning was highlighted in this study. PAN and TPU were both selected with differential viscosities to understand the phase-segregated internal supramolecular structures on functional surfaces of different length scales. The low-dimensional carbon nanofillers displayed a significant role in the topological orientation of the polymeric chains in TPU due to the presence of hard and soft segments in the geometry of TPU. The nano-hybrid shish-kebab-type microphase separation was observed on 1D nanofillers, whereas the anisotropic hierarchical microdomains were formed in the presence of 0D nanofillers. The 2D functional surface produced highly folded nanoscale lamellae by molecular interactions with polymeric chains. By combining different dimensional nanofillers, the hybrid 1D-2D networks created multifaceted structural hierarchies with epitaxial growth on the planar surface and shish-kebab geometry on the 1D functional backbone. Our study has demonstrated the significance of the configuration of nanoscale functional surfaces on the texture of polymeric chain assemblies during electrospinning for controlled flexible scaffolds.

'Nano on micro' hierarchical porous all carbon structures: an insight into interfacial interactions with bacteria.

Micron long carbon nanofibers (CNFs) were grown on porous carbon beads to give an active surface for rapid immobilization of guest molecules. The fabrication of nanostructures using a catalytic route involving chemical vapour deposition on a porous substrate was accomplished by the controlled synthesis of iron nanoclusters on the surface of porous carbon beads. The challenge of catalyst nanoparticle diffusion into the porous substrate was addressed by using iron coordinated ligand complexes and optimizing the loading percentage of metal salts onto beads. The effect of using tethered bottom up surface processed CNFs on the porous beads' morphologies was established using structural characterization. The protruding architecture of CNFs on the porous carbon surface was subjected to bacterial colonisation in order to determine the efficiency of cell conjugation onto hairy structures, particularly at a low concentration. The interfaces of immobilized bacteria on the textured surface were studied by varying the pH and external physical stimuli to check the biofilm formation. The strategy of fabricating all carbon porous beads, which had topologically controlled 'nano on micro' geometries, to give fast immobilization of guest molecules could be useful in the future for developing an active disinfectant surface.

Effect of Reinforcement at Length Scale for Polyurethane Cellular Scaffolds by Supramolecular Assemblies.

This study is aimed to represent the role of carbonaceous nanofillers to reinforce the commercially available polyurethane porous structure. The effect of dimensionality of fillers to anchor the construction of stable three-dimensional (3D) cellular architectures has been highlighted. The cellular frameworks of commercially available thermoplastic polyurethane (TPU) have been fabricated through the thermoreversible supramolecular self-assembly route. It was established that the minimum shrinkage of TPU lattice structures occurred when the solid-state network is strengthened by the topologically engineered 3D hierarchical nanofillers, where the amount of reinforcement was found to play a critical role. It has been established by series of structure-property correlations that reinforcing the cellular structure to endure the capillary stress is equally effective as supercritical drying for producing low-density porous morphologies. The removal of liquid phase from gel is as important as the presence of 3D fillers in the matrix for reinforcing the cellular structures when replacing the solvent phase with air to generate a two-phase solid-gas engineered morphology. The insight into the polyurethane network structure revealed that the dimensionality, amount, and distribution of fillers in the matrix are critical for reinforcing the cellular scaffolds in solid gel without any cross-linking.

TGF-ß1 Causes EMT by Regulating N-Acetyl Glucosaminyl Transferases via Downregulation of Non Muscle Myosin II-A through JNK/P38/PI3K Pathway in Lung Cancer.

BACKGROUND: Epithelial to mesenchymal transition (EMT) is a major determinant of cancer metastasis and is closely linked with TGF-ß1. Intracellular proteins, including E. Cadherin, N. Cadherin and Vimentin are directly related to EMT that affect cell migration and adhesion; on the other hand, non muscle myosin (NM) has a central role in cytokinesis, migration and adhesion. OBJECTIVE: We aimed to explore the association of EMT and metastasis with TGF-ß1 through regulation of non-muscle myosin II-A (NMII-A) and its interaction with Hexosamine Biosynthesis Pathway (HBP). METHOD: Protein expression changes were assessed by western blotting and immunofluorescent staining while transcription level changes were assessed by qRT-PCR. EMT was assessed by phenotypic analysis, wound healing, proliferation and transwell migration assay in vitro while in vivo studies were conducted in BALB/c nude mice for lung orthotopic and tail vein metastasis models. RESULTS: We demonstrated that regulation of JNK/ P38/PI3K by TGF-ß1 led to down expression of NMII-A which promoted EMT and lung cancer metastasis. This down expression of NMII-A conversely upregulated the expression of Core 2 N-acetyl Glucosaminyl Transferase mucin type (C2GnT-M) and further facilitated up-regulation and down-regulation of N-acetylglucosaminyltransferase (GnT) -V and -III respectively; moreover, NMII-A K.D cells showed 3 times more tendency to migrate towards brain in vivo. CONCLUSION: The study reports a novel pathway through which NMII-A negatively regulates EMT and metastasis via up regulation of C2GnT-M, GnT-V and down expression of GnT-III. These findings of lung cancer may further be required to study other cancer types.

Marsdenia tenacissima extract alters crucial metabolites in cancer, determined by 1 H NMR based metabolomics approach

ABSTRACT Altered metabolites level in the biosystems, is the potential cause of cancer, the primary reason of alteration of metabolism is change in nutrient consumption and waste excretion, as a result genetic mutation leads to cancer initiation and progression. Aberration of specific metabolites such as fumarate, succinate, 2-hydroxyglutarate may alter cell signaling. We collected liver and kidney samples and prepared for 1H NMR analysis, then executed NMR spectroscopy. We used a set of domestic R scripts to perform an unsupervised principal component analysis (PCA) and a supervised orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA). It signifies class discrimination for getting a clear separation, whereas PCA scores plot signifies the model group kept further away from the control group than drug group on the horizontal axis. In another PCA scores plots, most parts of the control group was overlapping with the drug group but was distant from the model group. Marsdenia tenacissima extract (MTE) (Chines name: Xiao-Ai-Ping, XAP) modulates level of crucial metabolites such as fumarate, lactate, succinate, determined by 1H NMR spectroscopy and their altered level contributes major role in cancer

Derivatization and interlaminar debonding of graphite-iron nanoparticle hybrid interfaces using Fenton chemistry.

The interfacial debonding of graphite lattices using iron (Fe) nanoparticles and Fenton's reagent is reported, towards the scalable production of few-layer graphene flakes. Acoustic cavitation via a sonochemical route was adapted to produce iron and iron oxide nanoparticles in the graphite matrix. The oxygenated species were introduced into the graphite lattice using a physical method, and then Fenton chemistry was utilized to generate localized hydroxyl radicals at the Fe nanoparticle-graphite interfaces for zipping and self-exfoliation of the defected graphite lattices. The functional groups were found to have been introduced predominately at the periphery of the flake, confirming that the lateral dimension of graphene had not been affected, and at the same time, good dispersion in organic solvents had been achieved. Defect engineering could be modulated at the organic-inorganic hybrid interfaces, in order to control the zipping rate and regulate the degree of functionalization and the lateral dimensions of the graphene sheet.

IDH mutations associated impact on related cancer epidemiology and subsequent effect toward HIF-1α.

Particular mutations in the isocitrate dehydrogenase gene (IDH) were discovered in several gliomas citing astrocytoma, oligodendroglioma, and glioblastoma multiform, but also in leukemia; these mutations were discovered in nearly all cases of secondary glioblastomas, they evolve from lower-grade gliomas, but are limited in primary high-grade glioblastoma multiform. These mutations distinctively produce (D)-2-hydroxyglutarate (D-2-HG) from alpha-ketoglutarate (α-KG). (D)-2-hydroxyglutarate is accumulated to very high concentrations which inhibit the function of enzymes that are dependent on alpha-ketoglutarate. This modification leads to a hyper-methylated state of DNA and histones, resulting in different gene expression that can activate oncogenes and inactivate tumor-suppressor genes. In our work we review the impact of the mutations that occur in IDH genes, we focus on their impact on distribution in cancer. As IDH mutations appear in many different conditions we expose the extent of IDH mutations and derivate their impact on cancer prognosis, diagnosis, and even their oncogenicity, we will also link their impact to HIF-1α and derivate some target and finally, we present some of the therapeutics under research and out on market.