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Here, resistive switching (RS) devices are fabricated using naturally abundant, nontoxic, biocompatible, and biodegradable biomaterials. For this purpose, 1D chitosan nanofibers (NFs), collagen NFs, and chitosan-collagen NFs are synthesized by using an electrospinning technique. Among different NFs, the collagen-NFs-based device shows promising RS characteristics. In particular, the optimized Ag/collagen NFs/fluorine-doped tin oxide RS device shows a voltage-tunable analog memory behavior and good nonvolatile memory properties. Moreover, it can also mimic various biological synaptic learning properties and can be used for pattern classification applications with the help of the spiking neural network. The time series analysis technique is employed to model and predict the switching variations of the RS device. Moreover, the collagen NFs have shown good cytotoxicity and anticancer properties, suggesting excellent biocompatibility as a switching layer. The biocompatibility of collagen NFs is explored with the help of NRK-52E (Normal Rat Kidney cell line) and MCF-7 (Michigan Cancer Foundation-7 cancer cell line). Additionally, the biodegradability of the device is evaluated through a physical transient test. This work provides a vital step toward developing a biocompatible and biodegradable switching material for sustainable nonvolatile memory and neuromorphic computing applications., (© 2024 Wiley‐VCH GmbH.)

The limited availability of cytokines in solid tumours hinders maintenance of the antitumour activity of chimeric antigen receptor (CAR) T cells. Cytokine receptor signalling pathways in CAR T cells can be activated by transgenic expression or injection of cytokines in the tumour, or by engineering the activation of cognate cytokine receptors. However, these strategies are constrained by toxicity arising from the activation of bystander cells, by the suboptimal biodistribution of the cytokines and by downregulation of the cognate receptor. Here we show that replacement of the extracellular domains of heterodimeric cytokine receptors in T cells with two leucine zipper motifs provides optimal Janus kinase/signal transducer and activator of transcription signalling. Such chimeric cytokine receptors, which can be generated for common γ-chain receptors, interleukin-10 and -12 receptors, enabled T cells to survive cytokine starvation without induction of autonomous cell growth, and augmented the effector function of CAR T cells in vitro in the setting of chronic antigen exposure and in human tumour xenografts in mice. As a modular design, leucine zippers can be used to generate constitutively active cytokine receptors in effector immune cells., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

This article describes a monolayer-coated gold nanoparticle-based transfection system for the delivery of microRNA (miRNA) into human osteosarcoma (HOS) cells. Two distinct ammonium-terminated adsorbates were used in this study, which provided a platform for ionic bonding of the miRNA onto gold nanoparticles (AuNPs). The custom-designed monolayer-coated gold nanoparticles were characterized by dynamic light scattering, gel mobility shift assay, transmission electron microscopy, ultraviolet-visible spectrometry, zeta potential, and X-ray photoelectron spectroscopy. The miRNA-loaded gold nanoparticles were transfected, and the level of intracellular miRNA delivered and taken up by cells was measured by Taqman qPCR. The overall analysis indicated a successful delivery of miRNA into the HOS cells at an ∼11,000-fold increase compared to nontreated cells.

Resistive-switching-based memory devices meet most of the requirements for use in next-generation information and communication technology applications, including standalone memory devices, neuromorphic hardware, and embedded sensing devices with on-chip storage, due to their low cost, excellent memory retention, compatibility with 3D integration, in-memory computing capabilities, and ease of fabrication. Electrochemical synthesis is the most widespread technique for the fabrication of state-of-the-art memory devices. The present review article summarizes the electrochemical approaches that have been proposed for the fabrication of switching, memristor, and memristive devices for memory storage, neuromorphic computing, and sensing applications, highlighting their various advantages and performance metrics. We also present the challenges and future research directions for this field in the concluding section.

Since the discovery of graphene, two-dimensional (2D) materials have gained widespread attention, owing to their appealing properties for various technological applications. Etched from their parent MAX phases, MXene is a newly emerged 2D material that was first reported in 2011. Since then, a lot of theoretical and experimental work has been done on more than 30 MXene structures for various applications. Given this, in the present review, we have tried to cover the multidisciplinary aspects of MXene including its structures, synthesis methods, and electronic, mechanical, optoelectronic, and magnetic properties. From an application point of view, we explore MXene-based supercapacitors, gas sensors, strain sensors, biosensors, electromagnetic interference shielding, microwave absorption, memristors, and artificial synaptic devices. Also, the impact of MXene-based materials on the characteristics of respective applications is systematically explored. This review provides the current status of MXene nanomaterials for various applications and possible future developments in this field.

Chimeric antigen receptor (CAR) T-cell therapy targeting T-cell acute lymphoblastic leukemia (T-ALL) faces limitations such as antigen selection and limited T-cell persistence. CD7 is an attractive antigen for targeting T-ALL, but overlapping expression on healthy T cells leads to fratricide of CD7-CAR T cells, requiring additional genetic modification. We took advantage of naturally occurring CD7- T cells to generate CD7-CAR (CD7-CARCD7-) T cells. CD7-CARCD7- T cells exhibited a predominantly CD4+ memory phenotype and had significant antitumor activity upon chronic antigen exposure in vitro and in xenograft mouse models. Based on these encouraging results, we next explored the utility of CD7- T cells for the immunotherapy of CD19+ hematological malignancies. Direct comparison of nonselected (bulk) CD19-CAR and CD19-CARCD7- T cells revealed that CD19-CARCD7- T cells had enhanced antitumor activity compared with their bulk counterparts in vitro and in vivo. Lastly, to gain insight into the behavior of CD19-CAR T cells with low levels of CD7 gene expression (CD7lo) in humans, we mined single-cell gene and T-cell receptor (TCR) expression data sets from our institutional CD19-CAR T-cell clinical study. CD19-CARCD7lo T cells were present in the initial CD19-CAR T-cell product and could be detected postinfusion. Intriguingly, the only functional CD4+ CD19-CAR T-cell cluster observed postinfusion exhibited CD7lo expression. Additionally, samples from patients responsive to therapy had a higher proportion of CD7lo T cells than nonresponders (NCT03573700). Thus, CARCD7- T cells have favorable biological characteristics and may present a promising T-cell subset for adoptive cell therapy of T-ALL and other hematological malignancies., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

T cells expressing CD19-specific chimeric antigen receptors (CD19-CARs) have potent antileukemia activity in pediatric and adult patients with relapsed and/or refractory B-cell acute lymphoblastic leukemia (B-ALL). However, not all patients achieve a complete response (CR), and a significant percentage relapse after CD19-CAR T-cell therapy due to T-cell intrinsic and/or extrinsic mechanisms. Thus, there is a need to evaluate new CD19-CAR T-cell products in patients to improve efficacy. We developed a phase 1/2 clinical study to evaluate an institutional autologous CD19-CAR T-cell product in pediatric patients with relapsed/refractory B-ALL. Here we report the outcome of the phase 1 study participants (n = 12). Treatment was well tolerated, with a low incidence of both cytokine release syndrome (any grade, n = 6) and neurotoxicity (any grade, n = 3). Nine out of 12 patients (75%) achieved a minimal residual disease-negative CR in the bone marrow (BM). High disease burden (≥40% morphologic blasts) before CAR T-cell infusion correlated with increased side effects and lower response rate, but not with CD19-CAR T-cell expansion. After infusion, CD8+ CAR T cells had a proliferative advantage over CD4+ CAR T cells and at peak expansion, had an effector memory phenotype with evidence of antigen-driven differentiation. Patients that proceeded to allogeneic hematopoietic cell transplantation (AlloHCT) had sustained, durable responses. In summary, the initial evaluation of our institutional CD19-CAR T-cell product demonstrates safety and efficacy while highlighting the impact of pre-infusion disease burden on outcomes. This trial was registered at www.clinicaltrials.gov as #NCT03573700., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

This research article presents a process control application of a single-input single-output (SISO) level control system using the combination of fast terminal sliding mode control (FTSMC) and optimization method. Non-dominated sorted genetic algorithm-ii (NSGA-ii); a modern optimization technique is used to optimized the parameters of FTSMC. Here, a comparative analysis of conventional sliding mode control (SMC), FTSMC, NSGA tuned FTSMC and NSGA-ii tuned FTSMC has being carried out through MATLAB/ Simulink. The performance indices such as integral absolute error (IAE), integral square error (ISE), and integration of weighted errors have been considered as the objective functions. The robustness of the controller is tested through real-time experimentation. The stability is obtained by using Lyapunov stability criteria. Simulation and experimental results show that NSGA-ii tuned FTSMC method outperforms the conventional methods and the error is converging to zero in a finite-time. Also, NSGA-ii tuned FTSMC provides better-estimated setpoint and disturbance rejection responses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 ISA. Published by Elsevier Ltd. All rights reserved.)

Developing CAR T cells for acute myeloid leukemia (AML) has been hampered by a paucity of targets that are expressed on AML blasts and not on hematopoietic progenitor cells (HPCs). Here we demonstrate that GRP78 is expressed on the cell surface of primary AML blasts but not HPCs. To target GRP78, we generate T cell expressing a GRP78-specific peptide-based CAR, which show evidence of minimal fratricide post activation/transduction and antigen-dependent T cell differentiation. GRP78-CAR T cells recognize and kill GRP78-positive AML cells without toxicity to HPCs. In vivo, GRP78-CAR T cells have significant anti-AML activity. To prevent antigen-dependent T cell differentiation, we block CAR signaling and GRP78 cell surface expression post activation by using dasatinib during GRP78-CAR T cell manufacturing. This significantly improves their effector function in vitro and in vivo. Thus, targeting cell surface GRP78-positive AML with CAR T cells is feasible, and warrants further active exploration., (© 2022. The Author(s).)

Background Aims: Vesicular stomatitis virus G (VSV-G)-pseudotyped lentiviral vectors (LVs) are widely used to reliably generate genetically modified, clinical-grade T-cell products. However, the results of genetically modifying natural killer (NK) cells with VSV-G LVs have been variable. The authors explored whether inhibition of the IKK-related protein kinases TBK1 and IKKε, key signaling molecules of the endosomal TLR4 pathway, which is activated by VSV-G, would enable the reliable transduction of NK cells by VSV-G LVs., Methods: The authors activated NK cells from peripheral blood mononuclear cells using standard procedures and transduced them with VSV-G LVs encoding a marker gene (yellow fluorescent protein [YFP]) or functional genes (chimeric antigen receptors [CARs], co-stimulatory molecules) in the presence of three TBK1/IKKε inhibitors (MRT67307, BX-795, amlexanox). NK cell transduction was evaluated by flow cytometry and/or western blot and the functionality of expressed CARs was evaluated in vitro., Results: Blocking TBK1/IKKε during transduction of NK cells enabled their efficient transduction by VSV-G LVs as judged by YFPexpression of 40-50%, with half maximal effective concentrations of 1.1 µM (MRT67307), 5 µM (BX-795) and 24.8 µM (amlexanox). Focusing on MRT67307, the authors successfully generated NK cells expressing CD19-CARs or HER2-CARs with an inducible co-stimulatory molecule. CAR NK cells exhibited increased cytolytic activity and ability to produce cytokines in comparison to untreated controls, confirming CAR functionality., Conclusions: The authors demonstrate that inhibition of TBK1/IKKε enables the reliable generation of genetically modified NK cells using VSV-G LVs. The authors' protocol can be readily adapted to generate clinical-grade NK cells and thus has the potential to facilitate the clinical evaluation of genetically modified NK cell-based therapeutics in the future., (Copyright © 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

The inability of chimeric antigen receptor (CAR) T cells to sustain their effector function after repeated exposure to tumor cells is a major obstacle to their success in patients with solid tumors. To overcome this limitation, we designed a novel chimeric cytokine receptor to create an autocrine loop that links activation-dependent GM-CSF production by CAR T cells to IL18 receptor signaling (GM18). Expression of GM18 in CAR T cells enhanced their effector function in an antigen- and activation-dependent manner. In repeat stimulation assays, which mimic chronic antigen exposure, CAR.GM18 T cells had a significantly greater ability to expand and produce cytokines in comparison with their unmodified counterparts targeting EPHA2 or HER2. In vivo , CAR.GM18 T cells induced tumor regression at cell doses at which standard CAR T cells were ineffective in two solid tumor xenograft models. Thus, our study highlights the potential of hijacking cytokines that are physiologically secreted by T cells to bolster their antitumor activity. SIGNIFICANCE: We designed a chimeric cytokine receptor (GM18) that links CAR T-cell activation to MYD88 signaling. GM18 endows CAR T cells with sustained effector function in the setting of chronic antigen exposure, resulting in potent antitumor activity in preclinical solid tumor models. This article is highlighted in the In This Issue feature, p. 1601 ., (©2021 American Association for Cancer Research.)

Human natural killer cell deficiency (NKD) arises from inborn errors of immunity that lead to impaired NK cell development, function, or both. Through the understanding of the biological perturbations in individuals with NKD, requirements for the generation of terminally mature functional innate effector cells can be elucidated. Here, we report a cause of NKD resulting from compound heterozygous mutations in minichromosomal maintenance complex member 10 (MCM10) that impaired NK cell maturation in a child with fatal susceptibility to CMV. MCM10 has not been previously associated with monogenic disease and plays a critical role in the activation and function of the eukaryotic DNA replisome. Through evaluation of patient primary fibroblasts, modeling patient mutations in fibroblast cell lines, and MCM10 knockdown in human NK cell lines, we have shown that loss of MCM10 function leads to impaired cell cycle progression and induction of DNA damage-response pathways. By modeling MCM10 deficiency in primary NK cell precursors, including patient-derived induced pluripotent stem cells, we further demonstrated that MCM10 is required for NK cell terminal maturation and acquisition of immunological system function. Together, these data define MCM10 as an NKD gene and provide biological insight into the requirement for the DNA replisome in human NK cell maturation and function.

A hydrothermal synthesis method was employed for the preparation of tin sulfide (α-SnS) microrod samples (SnS-A and SnS-B) using ethylenediamine and deionized water as the surfactant at ratios from 50 : 50 to 100 : 00. The atomic structures of the α-SnS microrods were studied using atomic pair distribution function (PDF) analysis and total synchrotron X-ray scattering data. The synchrotron X-ray diffraction (ScXRD) patterns and PDF data reveal that the structure of the SnS microrods is orthorhombic. From the refinement of the PDF, the first and second peaks correspond to nearest (Sn 2+ -S 2- ) and second nearest distances (Sn 2+ -Sn 2+ ) of 2.546 (0.003) Å and 4.106 (0.004) Å, and 2.527 (0.005) Å and 4.087 (0.006) Å for SnS-A and SnS-B samples, respectively. The TEM results show that samples SnS-A and SnS-B have a microrod structure, with microrod diameters of 800 nm and 500 nm with lengths of tens of micrometers, respectively. The SnS-A and SnS-B samples show a direct band gap of 1.6 eV and 2 eV, respectively, using the Kubelka-Munk transformation of the UV-visible spectra. The micro-Raman spectra of the SnS-A and SnS-B microrods exhibited an Ag mode of SnS at 228.4 and 223 cm -1 , respectively. The second peaks at 306.7, and 309 cm -1 are associated with the secondary phases of the SnS 2 phase, whereas the third broad peaks at 616.5, and 613 cm -1 revealed that there was a deformation mode of sulfate in the SnS-A and SnS-B samples., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Osteosarcoma (OS) is the most common primary pediatric malignancy of the bone having poor prognosis and long-term survival rates of less than 30% in patients with metastasis. MicroRNA-509 was reported to be downregulated in OS. We and others previously published that miR-509-3p can strongly attenuate cellular migration/invasion and sensitize ovarian cancer to cisplatin. Here, we show that overexpression of miR-509-3p inhibited migration of primary OS cell lines U2OS, HOS, and SaOS2 as well as metastatic derivatives 143B and LM7. miR-509-3p overexpression also inhibited proliferation and invasion of HOS and 143B cells and sensitized cells to cisplatin. Luciferase reporter assays using 3'-UTRs of predicted miR-509-3p targets associated with metastatic phenotypes revealed ARHGAP1 could be one of the downstream effectors of miR-509-3p in HOS. To find the global impact of miR-509-3p overexpression and cisplatin treatment we performed Reverse Phase Protein Analysis (RPPA). AXL, which has been reported to play a critical role in cisplatin resistance and confirmed as direct target of miR-509-3p was downregulated upon miR-509-3p treatment and further down-regulated upon miR-509-3p + cisplatin treatment. We propose that the miR-509-3p/AXL and miR-509-3p/ARHGAP1 axes have the potential to uncover new druggable targets for the treatment of drug resistant metastatic osteosarcoma.

Kyasanur forest disease virus (KFDV) is a tick-borne flavivirus identified in 1957 in the Karnataka state of India causing fatalities in monkeys and humans. Even after the introduction of a vaccine in the endemic areas, hundreds of cases are reported every year. Being a high-risk category pathogen, the studies on this virus in India were limited till the past decade. The growth characteristics of this virus in various mammalian cell lines have not yet been studied. In this study, we have demonstrated the growth pattern of virus in BHK-21, Vero E6, Vero CCL81, rhabdomyosarcoma, porcine stable kidney, and Pipistrellus ceylonicus bat embryo cell lines, and found BHK-21 to be the best. We have developed KFDV plaque reduction neutralization test for the first time.

Long noncoding RNAs (lncRNAs) are commonly dysregulated in tumors, but only a handful are known to play pathophysiological roles in cancer. We inferred lncRNAs that dysregulate cancer pathways, oncogenes, and tumor suppressors (cancer genes) by modeling their effects on the activity of transcription factors, RNA-binding proteins, and microRNAs in 5,185 TCGA tumors and 1,019 ENCODE assays. Our predictions included hundreds of candidate onco- and tumor-suppressor lncRNAs (cancer lncRNAs) whose somatic alterations account for the dysregulation of dozens of cancer genes and pathways in each of 14 tumor contexts. To demonstrate proof of concept, we showed that perturbations targeting OIP5-AS1 (an inferred tumor suppressor) and TUG1 and WT1-AS (inferred onco-lncRNAs) dysregulated cancer genes and altered proliferation of breast and gynecologic cancer cells. Our analysis indicates that, although most lncRNAs are dysregulated in a tumor-specific manner, some, including OIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergistically dysregulate cancer pathways in multiple tumor contexts., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Kyasanur forest disease (KFD) outbreak was confirmed in Dodamarg Taluka, Sindhudurga district (Maharashtra) in India during the year 2016. The rise in suspected KFD cases was reported in January 2016, peaked during March, and then declined gradually from April 2016. The outbreak was thoroughly investigated considering different socio-clinical parameters., Methods: Total, 488 suspected KFD cases were investigated using KFD specific real-time RT-PCR and anti-KFDV IgM enzyme-linked immunosorbent assay (ELISA). Sero-epidemiological survey was carried out in the affected area using anti-KFDV IgG ELISA., Results: Among suspected KFD cases, high age-specific attack rate (105.1 per 1000 persons) was observed in adults (aged 40-59 years). Out of 488 suspected KFD cases, 130 were laboratory confirmed. Of these, 54 cases were KFDV real-time RT-PCR positive, 66 cases were anti-KFDV IgM ELISA positive and 10 cases were positive by both the assays. Case fatality ratio among laboratory-confirmed KFD cases were 2.3% (3/130). Majority of laboratory-confirmed KFD cases (93.1%) had visited Western Ghats forest in Dodamarg for activities like working in cashew nut farms (79.8%), cashew nut fruit collection (76.6%), collection of firewood (68.5%) and dry leaves/grass (40.3%), etc., before the start of symptoms. Common clinical features included fever (100%), headache (93.1%), weakness (84.6%), and myalgia (83.1%). Hemorrhagic manifestations were observed in nearly one-third of the laboratory-confirmed KFD cases (28.5%). A seroprevalence of (9.7%, 72/745) was recorded in KFD-affected area and two neighboring villages (9.1%, 15/165). Serosurvey conducted in Ker village showed clinical to subclinical ratio of 6:1 in KFD-affected areas., Conclusion: This study confirms the outbreak of KFD Sindhudurg district with 130 cases. Detection of anti-KFDV IgG antibodies among the healthy population in KFD-affected area during the KFD outbreak suggested the past exposure of KFD infection. This outbreak investigation has helped health authorities in adopting KFD vaccination strategy for the population at risk.

As in most mature crude oil producing regions, asset divestment has commenced in Nigeria. Decommissioning and associated environmental liabilities are expected to become important problems requiring attention. Public and government engagement on decommissioning will be ineffective without information on cost of decommissioning liabilities, which are held confidential by oil companies. This study demonstrates a method to determine generic aggregate cost of decommissioning liabilities for Nigeria onshore fields, using non-proprietary data from annual financial reports of operating companies in Nigeria. The results can be used as basis for negotiation with operators and to help government in preparation for decommissioning risk., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Respiratory syncytial virus (RSV) is an important cause of acute lower respiratory tract infection (ALRI) in infants and young children globally. RSV presents two antigenic groups RSV-A and -B. Genetic variability is also very high within each group. RSV circulation varies year to year and even varies among different regions. Data on circulatory pattern of RSV are available from other parts of India except Kerala. The aim of the study was to generate data about groups and genotypes of circulating RSV in Kerala. In this study, RSV positive samples received during January, 2012 to December, 2014 were used for genetic characterization. The samples were tested by using nucleocapsid (N) gene-based conventional multiplex reverse transcriptase polymerase chain reaction (RT-PCR) to identify the RSV group. Genotyping was done by nucleotide sequencing of the C-terminal region of the glycoprotein (G) gene. Out of the 130 patient samples tested, 49 samples were positive for RSV. Among the positive samples, 32 belong to the RSV-A and 17 belong to RSV-B virus. Phylogenetic analysis revealed that all RSV-A sequences (n = 22) belonged to NA1 genotype and five of the sequences showed the novel 72 nucleotide duplication and clustered into the newly designated ON1 genotype. All RSV-B sequences (n = 17) were clustered into the BA (BA9 and 10) genotype. From this study, we concluded both RSV-A and -B were co-circulated in Kerala and RSV-A was observed predominantly in 2012 and RSV-B in 2014. As per our best of knowledge, BA10 genotype is first observed in India., (© 2017 Wiley Periodicals, Inc.)

Purpose of the Study: Rutin (RUT) and quercetin (QRT) which are dietary compounds were investigated for their ability to protect against ionizing radiation (IR)-induced genotoxicity in human lymphocytes., Materials and Methods: The radiation antagonistic potential of RUT and QRT was assessed by alkaline comet and cytokinesis-block micronucleus (CBMN) assay., Results: Treatment of lymphocytes with RUT and QRT (25 μg/ml) prior exposure to 2 Gy gamma radiation resulted in a significant reduction of frequency of micronuclei as compared to the control set of cells evaluated by CBMN assay. Similarly, treatment of lymphocytes with RUT and QRT before radiation exposure showed significant decrease in the DNA damage as assessed by comet parameters, such as percent tail DNA and olive tail moment., Conclusion: The study demonstrates the protective effect of RUT and QRT against IR-induced DNA damage in human lymphocytes, which may be partly attributed to scavenging of IR-induced free radicals and also by the inhibition of IR-induced oxidative stress., Competing Interests: There are no conflicts of interest.

This Article describes the generation and study of surfaces modified with custom-crafted poly(l-lysine) (PLL) coatings for use in the loading and delivery of single-stranded DNA (ssDNA). The experimental strategy utilizes bidentate dithiol adsorbates to generate stably bound azide-terminated self-assembled monolayers (SAMs) on gold possessing an oligo(ethylene glycol) (OEG) spacer. Consequent to the molecular assembly on gold, the azide termini are covalently attached to a maleimide linker moiety via a copper-catalyzed azide-alkyne "click" reaction. Functionalization with maleimide provides a platform for the subsequent attachment of cysteine-terminated poly(l-lysine) (PLL), thus forming a suitable surface for the loading of ssDNA via electrostatic interactions. In efforts to maximize DNA loading, we generate SAMs containing mixtures of short and long PLL segments and explore the DNA-loading capability of the various PLL SAMs. We then use thermal increases to trigger the release of the ssDNA from the surface. By examining the loading and release of ssDNA using these new two-dimensional systems, we gain preliminary insight into the potential efficacy of this approach when using three-dimensional gold nanostructure systems in future gene-delivery and biosensing applications.

Ovarian cancer presents as an aggressive, advanced stage cancer with widespread metastases that depend primarily on multicellular spheroids in the peritoneal fluid. To identify new druggable pathways related to metastatic progression and spheroid formation, we integrated microRNA and mRNA sequencing data from 293 tumors from The Cancer Genome Atlas (TCGA) ovarian cancer cohort. We identified miR-509-3p as a clinically significant microRNA that is more abundant in patients with favorable survival in both the TCGA cohort (P = 2.3E-3), and, by in situ hybridization (ISH), in an independent cohort of 157 tumors (P < 1.0E-3). We found that miR-509-3p attenuated migration and disrupted multi-cellular spheroids in HEYA8, OVCAR8, SKOV3, OVCAR3, OVCAR4 and OVCAR5 cell lines. Consistent with disrupted spheroid formation, in TCGA data miR-509-3p's most strongly anti-correlated predicted targets were enriched in components of the extracellular matrix (ECM). We validated the Hippo pathway effector YAP1 as a direct miR-509-3p target. We showed that siRNA to YAP1 replicated 90% of miR-509-3p-mediated migration attenuation in OVCAR8, which contained high levels of YAP1 protein, but not in the other cell lines, in which levels of this protein were moderate to low. Our data suggest that the miR-509-3p/YAP1 axis may be a new druggable target in cancers with high YAP1, and we propose that therapeutically targeting the miR-509-3p/YAP1/ECM axis may disrupt early steps in multi-cellular spheroid formation, and so inhibit metastasis in epithelial ovarian cancer and potentially in other cancers., Competing Interests: The authors declare no conflicts of interests.

Background: Ionizing radiation induces a variety of genetic damages through the formation free radicals such as reactive oxygen species (ROS). Appropriate antioxidant intervention may inhibit or reduce free radical toxicity and thus offer protection against radiation. Rutin (RUT) and quercetin (QRT) are flavonoids known to be potent dietary antioxidants., Methods: The present study tested the antigenotoxic effect of RUT and QRT in vivo against radiation- induced chromosomal damage. Swiss albino mice were administered orally with RUT and QRT (10 and 20 mg/kg b.wt.) once daily for five consecutive days. One hour after the last administration of RUT and QRT on the fifth day, the animals were whole body exposed to 3 Gy gamma radiation. The anti-genotoxic potential was assessed in terms of chromosomal aberrations, micronucleus test, and alkaline comet assay., Results: Significant decline in dicentric formation was observed in RUT and QRT treated group. Further, the antigenotoxic potential of RUT and QRT caused a significant (p < 0.001) reduction in micronucleated polychromatic, normochromatic erythrocytes; increased PCE/NCE ratio was observed in the RUT and QRT treated group. Administration of RUT and QRT before irradiation resulted in a significant (p < 0.01) decrease in the DNA damage at the post-irradiation time when compared with irradiation alone group., Conclusions: Present findings demonstrate the potential of RUT and QRT in mitigating radiation-induced mortality and cytogenetic damage, which may be attributed to scavenging of radiation-induced free radicals.

The radioprotective potential of bioflavonoid, rutin (RUT) and quercetin (QRT) was investigated in Swiss albino mice exposed to gamma radiation. The radioprotective potential of RUT and QRT was assessed in pre-treatment group of mice followed on radiation-induced changes in glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (LPO) levels were also analyzed. Elevation in the GSH, GST, SOD, CAT, and decreased LPO levels were observed in RUT and QRT pretreated group when compared to the irradiated animals. Furthermore, it was observed that RUT and QRT treatment was found to inhibit various free radicals generated in vitro, viz., 2,2-diphenyl-1-picrylhydrazyl(DPPH), O2, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS)(+), and OH in a concentration-dependent manner. This study clearly demonstrates the free radical scavenging action of RUT and QRT, indicating that it may have its potential as a radioprotective agent. Furthermore, the presence of a phenolic group in RUT and QRT is known to contribute to scavenging the radiation-induced free radicals and inhibition of oxidative stress. Present findings demonstrate the potential of RUT and QRT in mitigating radiation-induced oxidative stress, which may be attributed to the inhibition of radiation-induced decline in the endogenous antioxidant levels and scavenging of radiation-induced free radicals.

Context: Radiation therapy is the prime treatment modality against various cancers. However, its use is limited due to the effects of radiation on normal tissues., Aims: In view of this, present study was carried out to evaluate the radioprotective potential of Rutin (RUT) and Quercetin (QRT) in Swiss Albino mice exposed to the whole body gamma radiation. To gain insight into the mechanism of action, RUT and QRT were tested for its antioxidant levels in mice., Settings and Designs: Optimum protective dose of RUT and QRT against radiation induced animal mortality was selected by administration of various doses of the RUT and QRT before 10 Gy gamma irradiation., Materials and Methods: Swiss Albino mice were used for the assessment of radiation induced sickness along with the survival analysis and anti-oxidative properties of RUT and QRT., Statistical Analysis Used: Survival studies were determined using the Kaplan-Meier survival curves., Results: The maximum survival was observed with 10 mg/kg. b. wt. and 20 mg/kg. b. wt. of RUT and QRT respectively, this dose was considered as an optimal dose for radioprotection. Treatment of mice with RUT and QRT before irradiation delayed the onset of mortality as compared with the untreated irradiated controls. The oral administration of RUT and QRT resulted in an increase in the radiation tolerance and the dose reduction factor was found to be 1.15 and 1.11 respectively. RUT and QRT pre-treatment significantly (P < 0.01) elevated levels of reduced glutathione, glutathione-S-transferase, catalase, Superoxide dismutase, and a decreased lipid peroxidation in mouse liver homogenate at 24 h after exposure to 4.5 Gy., Conclusions: Present findings demonstrate the potential of RUT and QRT in mitigating radiation-induced mortality, which may be attributed to the elevation in the antioxidant status, anti-lipid peroxidative potential.

The heart is remarkably resilient even in the face of heavy parasite sequestration and other vital organ dysfunction, and deaths from cardiac arrhythmias in severe malaria are rare. Malaria may prove fatal for patients with pre-existing cardiac failure due to valvular stenosis or myocardial disease. High grade fever, parasitaemia, and fluid overload can all contribute to the problem. Cardiac arrhythmias are very rarely observed in severe falciparum malaria. An attempt has been made to evaluate the risk factors for cardiovascular diseases in malaria infected patients. In the present study the levels of total cholesterol, low density lipoproteins, triglycerides were high and the levels of high density lipoproteins were low in malaria infected patients compared to controls. The markers of free radical induced injury i.e. malondialdehyde were high. The study therefore suggests the importance of assessing these markers of oxidative stress along with the other routine investigations in malaria infected patients for initiating therapy in addition to primary and secondary preventive measures to mitigate the devastating consequences hyperlipidemia in malaria infected patients leading to cardiovascular diseases.

This paper reports on experimental investigation of the rheological behavior of copper oxide nanoparticles dispersed in a 60:40 propylene glycol and water mixture. Nanofluids of a particle volume concentration from 0 to 6% have been tested in this study. The experiments were conducted over a temperature range of -35 degrees C to 50 degrees C to establish their behavior for use as a heat transfer fluid in cold climates. The experiments reveal that this nanofluid in the range of particle volume percentage tested exhibits a Newtonian behavior. A new exponential correlation has been developed from the experimental data, which expresses the viscosity as a function of particle volume percent and the temperature of the nanofluid. The slope of relative viscosity curve was found to be higher at lower temperatures.