Search results for: anticancer gelatin nanoparticles

Authors: Sezen Gurdag, Ayse Ebru Akin

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There is a growing concern all over the world on the health effect of the formaldehyde emission coming from the adhesive used in the MDF production. In this research, we investigated the effect of nanoparticle addition such as nanoclay and halloysite into urea-formadehyde resin on the total emitted formaldehyde from MDF plates produced using the resin modified as such. First, the curing behavior of the resin was studied by monitoring the pH, curing time, solid content, density and viscosity of the modified resin in comparison to the reference resin with no added nanoparticle. The dosing of the nanoparticle in the dry resin was kept at 1wt%, 3wt% or 5wt%. Consecutively, the resin was used in the production of 50X50 cm MDF samples using laboratory scale press line with full automation system. Modulus of elasticity, bending strength, internal bonding strength, water absorption were also measured in addition to the main interested parameter formaldehyde emission levels which is determined via spectrometric technique following an extraction procedure. Threshold values for nanoparticle dosing levels were determined to be 5wt% for both nanoparticles. However, the reinforcing behavior was observed to be occurring at different levels in comparison to the reference plates with each nanoparticle such that the level of reinforcement with nanoclay was shown to be more favorable than the addition of halloysite due to higher surface area available with the former. In relation, formaldehyde emission levels were observed to be following a similar trend where addition of 5wt% nanoclay into the urea-formaldehyde adhesive helped decrease the formaldehyde emission up to 40% whereas addition of halloysite at its threshold level demonstrated as the same level, i.e., 5wt%, produced an improvement of 18% only.

Keywords: halloysite, nanoclay, fiberboard, urea-formaldehyde adhesive

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Authors: Khamael M. Abualnaja, Lidija Šiller, Ben R. Horrocks

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Surface enhanced Raman spectroscopy (SERS) of Silicon nano crystals (SiNCs) were obtained using two different laser excitations: 488 nm and 514.5 nm. Silver nano particles were used as plasmonics metal nano particles due to a robust SERS effect that observed when they mixed with SiNCs. SiNCs have been characterized by scanning electron microscopy (SEM), high resolution transmission electron microscopy (HRTEM), atomic force microscopy (AFM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). It is found that the SiNCs are crystalline with an average diameter of 65 nm and FCC lattice. Silver nano particles (AgNPs) of two different sizes were synthesized using photo chemical reduction of AgNO3 with sodium dodecyl sulfate (SDS). The synthesized AgNPs have a polycrystalline structure with an average particle diameter of 100 nm and 30 nm, respectively. A significant enhancement in the SERS intensity was observed for AgNPs100/SiNCs and AgNPs30/SiNCs mixtures increasing up to 9 and 3 times respectively using 488 nm intensity; whereas the intensity of the SERS signal increased up to 7 and 2 times respectively, using 514.5 nm excitation source. The enhancement in SERS intensities occurs as a result of the coupling between the excitation laser light and the plasmon bands of AgNPs; thus this intense field at AgNPs surface couples strongly to SiNCs. The results provide good consensus between the wavelength of the laser excitation source and surface plasmon resonance absorption band of silver nano particles consider to be an important requirement in SERS experiments.

Keywords: silicon nanocrystals (SiNCs), silver nanoparticles (AgNPs), surface enhanced raman spectroscopy (SERS)

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Authors: Yu-Shan Wu, Po-Liang Lai, I-Ming Chu

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Poly(methylmethacrylate)(PMMA) is the most frequently used bone void filler for vertebral augmentation in osteoporotic fracture. PMMA bone cement not only exhibits strong mechanical properties but also can fabricate according to the shape of bone defect. However, the adhesion between the PMMA-based cement and the adjacent bone is usually weak and as PMMA bone cement is inherently bioinert. The combination of bioceramics and polymers as composites may increase cell adhesion and improve biocompatibility. The nano-hydroxyapatite(HAP) not only plays a significant role in maintaining the properties of the natural bone but also offers a favorable environment for osteoconduction, protein adhesion, and osteoblast proliferation. However, defects and cracks can form at the polymer/ceramics interface, resulting in uneven distribution of stress and subsequent inferior mechanical strength. Surface-modified HAP nano-crystals were prepared by chemically grafting poly(ε-caprolactone)(PCL) on surface-modified nano-HAP surface to increase the affinity of polymer/ceramic phases .Thus, incorporation of surface-modified nano-hydroxyapatite (EC-HAP) may not only improve the interfacial adhesion between cement and bone and between nanoparticles and cement, but also increase biocompatibility. In this research, PMMA mixing with 0, 5, 10, 15, 20, 25 and 30 wt% EC-HAP were examined. MC3T3-E1 cells were used for the biological evaluation of the response to the cements in vitro. Morphology was observed using scanning electron microscopy (SEM). Mechanical properties of HAP/PMMA and EC-HAP/PMMA cement were investigated by compression test. Surface wettability of the cements was measured by contact angles.

Keywords: bone cement, biocompatibility, nano-hydroxyapatite, polycaprolactone, PMMA, surface grafting

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Authors: Zeeshan Ahmed, Ajinkya Sarode, Pratik Basarkar, Atul Bhargav, Debjyoti Banerjee

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The use of CO₂ in oil recovery and in CO₂ capture and storage is gaining traction in recent years. These applications involve heat transfer between CO₂ and the base fluid, and hence, there arises a need to improve the thermal conductivity of CO₂ to increase the process efficiency and reduce cost. One way to improve the thermal conductivity is through nanoparticle addition in the base fluid. The nanofluid model in this study consisted of copper (Cu) nanoparticles in varying concentrations with CO₂ as a base fluid. No experimental data are available on thermal conductivity of CO₂ based nanofluid. Molecular dynamics (MD) simulations are an increasingly adopted tool to perform preliminary assessments of nanoparticle (NP) fluid interactions. In this study, the effect of the formation of a nanolayer (or molecular layering) at the gas-solid interface on thermal conductivity is investigated using equilibrium MD simulations by varying NP diameter and keeping the volume fraction (1.413%) of nanofluid constant to check the diameter effect of NP on the nanolayer and thermal conductivity. A dense semi-solid fluid layer was seen to be formed at the NP-gas interface, and the thickness increases with increase in particle diameter, which also moves with the NP Brownian motion. Density distribution has been done to see the effect of nanolayer, and its thickness around the NP. These findings are extremely beneficial, especially to industries employed in oil recovery as increased thermal conductivity of CO₂ will lead to enhanced oil recovery and thermal energy storage.

Keywords: copper-CO2 nanofluid, molecular dynamics simulation, molecular interfacial layer, thermal conductivity

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Authors: Behzad Ahdiharab, Senol Baskaya, Tamer Calisir

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Heat exchangers are one of the most widely used systems in factories, refineries etc. In this study, natural convection heat transfer using nano-fluids in between two cylinders is numerically investigated. The inner and outer cylinders are kept at constant temperatures. One of the most important assumptions in the project is that the working fluid is non-Newtonian. In recent years, the use of nano-fluids in industrial applications has increased profoundly. In this study, nano-Newtonian fluids containing metal particles with high heat transfer coefficients have been used. All fluid properties such as homogeneity has been calculated. In the present study, solutions have been obtained under unsteady conditions, base fluid was water, and effects of various parameters on heat transfer have been investigated. These parameters are Rayleigh number (103 < Ra < 106), power-law index (0.6 < n < 1.4), aspect ratio (0 < AR < 0.8), nano-particle composition, horizontal and vertical displacement of the inner cylinder, rotation of the inner cylinder, and volume fraction of nanoparticles. Results such as the internal cylinder average and local Nusselt number variations, contours of temperature, flow lines are presented. The results are also discussed in detail. From the validation study performed it was found that a very good agreement exists between the present results and those from the open literature. It was found out that the heat transfer is always affected by the investigated parameters. However, the degree to which the heat transfer is affected does change in a wide range.

Keywords: heat transfer, circular space, non-Newtonian, nano fluid, computational fluid dynamics.

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Authors: Tinomuvonga Manenji Zhou, Eubert Mahofa, Tatenda Crispen Madzokere

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The nanostructured formulation can increase fertilizer efficacy and uptake ratio of the soil nutrients in agriculture production and save fertilizer resources. Controlled release modes have properties of both release rate and release pattern of nutrients, for fertilizers that are soluble in water might be correctly controlled. Nanoparticles can reduce the rate at which fertilizer nutrients are in the soil by leaching. A slow release NPK-hydroxyapatite nano hybrid fertilizer was synthesized using exfoliated bentonite as filler material. A simple, scalable method was used to synthesize the nitrogen-phosphorus hydroxyapatite nano fertilizer, where calcium hydroxide, phosphoric acid, and urea were used as precursor material, followed by the incorporation of potassium through a liquid grinding method. The product obtained was an NPK-hydroxyapatite nano hybrid fertilizer. A quantitative analysis was done to determine the percentage of nitrogen, phosphorus, and potassium in the hybrid fertilizer. AAS was used to determine the percentage of potassium in the fertilizer. An accelerated water test was conducted to compare the nutrient release behavior of nutrients between the synthesized NPK-hydroxyapatite nano hybrid fertilizer and commercial NPK fertilizer. The rate of release of Nitrogen, phosphorus, and potassium was significantly lower in the synthesized NPK hydroxyapatite nano hybrid fertilizer than in the convectional NPK fertilizer. The synthesized fertilizer was characterized using XRD. NPK hydroxyapatite nano hybrid fertilizer encapsulated in exfoliated bentonite thus prepared can be used as an environmentally friendly fertilizer formulation which could be extended to solve one of the major problems faced in the global fertilization of low nitrogen, phosphorus, and potassium use efficiency in agriculture.

Keywords: NPK hydroxyapatite nano hybrid fertilizer, bentonite, encapsulation, low release

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Authors: Tumelo W. P. Seadira, Thabang Ntho, Cornelius M. Masuku, Michael S. Scurrell

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A ternary Cu/TiO2/rGO photocatalysts was prepared using solvothermal method. Firstly, pure anatase TiO2 hollow spheres were prepared with titanium butoxide, ethanol, ammonium sulphate, and urea via hydrothermal method; and Cu nanoparticles were subsequently loaded on the surface of the hollow spheres by wet impregnation. During the solvothermal process, the deposition and well dispersion of Cu-TiO2 hollow spheres composites onto the graphene oxide surface, as well as the reduction of graphene oxide to graphene were achieved. The morphological and structural properties of the prepared samples were characterized by Brunauer-Emmett-Tellet (BET), X-ray Diffraction (XRD), Scanning Electron Microscope (SEM), Transmission Electron Microscopy (TEM), and UV-vis DRS, and photoelectrochemical. The activities of the prepared catalysts were tested for hydrogen production via simultaneous photocatalytic water-splitting and glycerol reforming under visible light irradiation. The excellent photocatalytic activity of the Cu-TiO2-hollow-spheres/rGO catalyst was attributed the rGO which acts as both storage and transferor of electrons generated at the Cu and TiO2 heterojunction, thus increasing the electron-hole pairs separation. This paper reports the preparation of photocatalyst which is highly active by coupling reduced graphene oxide with nano-structured TiO2 with high surface area that can efficiently harvest the visible light for effective water-splitting and glycerol photocatalytic reforming in order to achieve efficient hydrogen evolution.

Keywords: glycerol reforming, hydrogen evolution, graphene oxide, Cu/TiO2-hollow-spheres/rGO

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Authors: Mathias Schlenk, Susanne Seibt, Sabine Rosenfeldt, Josef Breu, Stephan Foerster

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Thin liquid jets on micrometer scale play an important role in processing such as in fiber fabrication, inkjet printing, but also for sample delivery in modern synchrotron X-ray devices. In all these cases the liquid jets contain solvents and dissolved materials such as polymers, nanoparticles, fibers pigments or proteins. As liquid flow in liquid jets differs significantly from flow in capillaries and microchannels, particle localization and orientation will also be different. This is of critical importance for applications, which depend on well-defined homogeneous particle and fiber distribution and orientation in liquid jets. Investigations of particle orientation in liquid microjets of diluted solutions have been rare, despite their importance. With the arise of micro-focused X-ray beams it has become possible to scan across samples with micrometer resolution to locally analyse structure and orientation of the samples. In the present work, we used this method to scan across liquid microjets to determine the local distribution and orientation of anisotropic particles. The compromise wormlike block copolymer micelles as an example of long flexible fibrous structures, hectorite materials as a model of extended nanosheet structures, and gold nanorods as an illustration of short stiff cylinders to comprise all relevant anisotropic geometries. We find that due to the different velocity profile in the liquid jet, which resembles plug flow, the orientation of the particles which was generated in the capillary is lost or changed into non-oriented or bi-axially orientations depending on the geometrical shape of the particle.

Keywords: anisotropic particles, liquid microjets, reorientation, SAXS

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Authors: Tien S. H. Pham, Peter J. Mahon, Aimin Yu

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The detection of drug molecules by voltammetry has attracted great interest over the past years. However, many drug molecules exhibit poor electrochemical signals at common electrodes which result in low sensitivity in detection. An efficient way to overcome this problem is to modify electrodes with functional materials. Since discovered in 2004, graphene (or reduced graphene oxide) has emerged as one of the most studied two-dimensional carbon materials in condensed matter physics, electrochemistry, and so on due to its exceptional physicochemical properties. Additionally, the continuous development of technology has opened the new window for the successful fabrications of many novel graphene-based nanomaterials to serve in electrochemical analysis. This research aims to synthesize and characterize gold nanoparticle coated beta-cyclodextrin functionalized reduced graphene oxide (Au NP–β-CD–RGO) nanocomposites with highly conductive and strongly electro-catalytic properties as well as excellent supramolecular recognition abilities for the modification of electrodes. The electrochemical responses of ciprofloxacin at the as-prepared nanocomposite modified electrode was effectively amplified was much higher in comparison with that at the bare electrode. The linear concentration range was from 0.01 to 120 µM, with a detection limit of 2.7 nM using differential pulse voltammetry. Thus, Au NP–β-CD–RGO nanocomposite has great potential as an ideal material to construct sensitive sensors for the electrochemical determination of ciprofloxacin or similar antibacterial drugs in the future based on its excellent stability, selectivity, and reproducibility.

Keywords: Au nanoparticles, β-CD, ciprofloxacin, electrochemical determination, graphene based nanomaterials

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Authors: Mallikarjunachari Gangapuram

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The design of stimuli-responsive hydrogel nanocomposite thin films is gaining significant attention in these days due to its wide variety of applications. Soft microrobots, drug delivery, biosensors, regenerative medicine, bacterial adhesion, energy storage and wound dressing are few advanced applications in different fields. In this research work, the nanomechanical properties of composite thin films of 20 microns were tuned by applying homogeneous external DC, and AC magnetic fields of magnitudes 0.05 T and 0.1 T. Polyvinyl alcohol (PVA) used as a matrix material and elliptical hematite nanoparticles (ratio of the length of the major axis to the length of the minor axis is 140.59 ± 1.072 nm/52.84 ± 1.072 nm) used as filler materials to prepare the nanocomposite thin films. Both quasi-static nanoindentation, Nano Dynamic Mechanical Analysis (Nano-DMA) tests were performed to characterize the viscoelastic properties of PVA, PVA+Hematite (0.1% wt, 2% wt and 4% wt) nanocomposites. Different properties such as storage modulus, loss modulus, hardness, and Er/H were carefully analyzed. The increase in storage modulus, hardness, Er/H and a decrease in loss modulus were observed with increasing concentration and DC magnetic field followed by AC magnetic field. Contact angle and ATR-FTIR experiments were conducted to understand the molecular mechanisms such as hydrogen bond formation, crosslinking density, and particle-particle interactions. This systematic study is helpful in design and modeling of magnetic responsive hydrogel nanocomposite thin films for biomedical applications.

Keywords: hematite, hydrogel, nanoindentation, nano-DMA

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Authors: Nasrin Hosseinzad, Ramin Ghasemi Shayan

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Chemotherapy is the most common procedure in the treatment of advanced cancers but is justsoberlyoperativeand toxic. Nevertheless, the efficiency of chemotherapy is restrictedowing to multiple drug resistance(MDR). Lately, plentiful preclinical experiments have revealedthatPaclitaxel-Curcumin could be an ultimateapproach to converse MDR and synergistically increase their efficiency. The connotationsamongst B-cell-lymphoma2(BCL-2) and multi-drug-resistance-associated-P-glycoprotein(MDR1) consequence of patients forecast the efficiency of paclitaxel-built chemoradiotherapy. There are evidences of the efficacy of paclitaxel in the treatment of surface-transmission of bladder-cell-carcinoma by manipulating bio-adhesive microspheres accomplishedthroughout measured release of drug at urine epithelium. In Genetically-Modified method, muco-adhesive oily constructionoftricaprylin, Tween 80, and paclitaxel group showed slighter toxicity than control in therapeutic dose. Postoperative chemotherapy-Paclitaxel might be more advantageous for survival than adjuvant chemo-radio-therapy, and coulddiminish postoperative complications in cervical cancer patients underwent a radical hysterectomy.HA-Se-PTX(Hyaluronic acid, Selenium, Paclitaxel) nanoparticles could observablyconstrain the proliferation, transmission, and invasion of metastatic cells and apoptosis. Furthermore, they exhibitedvast in vivo anti-tumor effect. Additionally, HA-Se-PTX displayedminor toxicity on mice-chef-organs. Briefly, HA-Se-PTX mightprogress into a respectednano-scale agentinrespiratory cancers. To sum up, Paclitaxel is considered a profitable anti-cancer drug in the treatment and anti-progress symptoms in malignant cancers.

Keywords: cancer, paclitaxel, chemotherapy, tumor

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Authors: Mohammad Javad Afroughi, Farjad Falahati, Larry W. Kostiuk, Jason S. Olfert

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This study investigates the physical characteristics of nanoparticles generated during pyrolysis of methane in hot products of a premixed propane-air flame. An inverted burner is designed to provide a laminar premixed propane-air flame (35 SLPM) then introduce methane co-flow to be pyrolyzed within a closed cylindrical chamber (20 cm in diameter and 68 cm in length). The formed products are discharged through an exhaust with a sampling branch to measure emission characteristics. Carbon particles are sampled with a preheated nitrogen dilution system, and the size distribution of particles formed by pyrolysis is measured by a scanning mobility particle sizer (SMPS). Dilution ratio is calculated using simultaneously measured CO2 concentrations in the exhaust products and diluted samples. Results show that particle size distribution (PSD) is strongly affected by dilution ratio and preheating temperature. PSD becomes unstable at high dilution ratios (typically above 700 times) and/or low preheating temperatures (below 40° C). At a suitable dilution ratio of 55 and preheating temperature up to 70° C, the median diameter of PSD increases from 20 to 220 nm following the introduction of 0.5 SLPM of methane to the propane-air premixed flame. Furthermore, with pyrolysis of methane, total particle number concentration and estimated total mass concentration of particles in the size range of 14 to 700 nm, increase from 1.12 to 3.90 *107 cm-3 and from 0.11 to 154 µg L-1, respectively.

Keywords: laminar premixed flame, methane pyrolysis, nanoparticle physical characteristics, particle mass concentration, particle number concentration, particle size distribution (PSD)

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Authors: Avijit Dey, Antony Gomes, Subir Chandra Dasgupta

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Tea (Camellia sinensis) is the most popular beverages in the world and is ranked second after the water. Tea has been considered as a health promoting beverage since ancient times due to its health-promoting activity. Recently, immunomodulatory, anti-arthritic, antioxidant, anticancer and cardioprotective activity of tea has been established. Very few studies have demonstrated the effect of high dose of black tea on health. The aim of the present study was to evaluate the role of low & high dose of Black Tea Extract (BTE) on the different physiological parameters of mother and pups during prenatal and postnatal developmental period in the experimental rodent. BTE was orally administered in LD (50mg BTE/kg/day) and HD (100mg BTE/kg/day) except control groups of rats (n=6/group) throughout the prenatal (day 0-21) and postnatal (day 21-42) periods. During prenatal period (0, 7th, 14th, 20th days) body weight, urinary calcium, magnesium, urea and creatinine was measured. In postnatal period physical (0, 10th, 21th days) parameters of pups like body weight, cranial length, cranial diameter, neck width, tail length, craniosacral length of pups were analyzed. Liver and lungs from pups and kidney spleen, etc. from mothers were collected on day 42 for histopathological studies. The comparative urine strip and morphology of RBC was also analyzed by SEM from mothers of different groups on day 42. The level of cytokines like IL-1alpha, IL-1beta, IL-6, IL-10, TNF-alpha were analysed by enzyme-linked immunosorbent assay (ELISA) on day 0, day 20 and day 42. The body weight of LD and HD mothers were also significantly (P<0.05) less than control mothers at 20th day of pregnancy and there was also significant changes in urinary calcium, urea, creatinine. The bio morphometric analysis of pups showed significant alteration (P<0.05) in HD groups relative to control. Some histological alterations were also observed in pups and mothers. Comparative urine strip analysis and morphology of RBC showed significant changes in treated groups. LD and HD treated mothers showed an increase in proinflammatory cytokines like IL-1beta, TNF-alpha and decrease in anti-inflammatory cytokine-like IL-10 on day 20 compared to PC mothers. This study clearly indicated that high dose of BTE possesses detrimental effect on pregnant mother and the pup. Further studies are in progress to elucidate the molecular mechanism of actions. This project work has been sponsored by National Tea Research Foundation vide Project Sanction No.: 17 (305)/2013/4423 dated 11th March, 2014. All experimental protocols described in the study were approved by animal ethics committee.

Keywords: black tea extract, pregnancy, prenatal and postnatal development, inflammation

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Authors: Munir Ashraf, Shagufta Riaz

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Personal protective equipment (PPE) and bioactive textiles are highly important for the health care of front line hospital workers, patients, and the general population to be safe from highly infectious diseases. This was even more critical in the wake of COVID-19 outbreak. Most of the medical textiles are inactive against various viruses and bacteria, hence there is a need to wash them frequently to avoid the spread of microorganisms. According to survey conducted by the world health organization, more than 500 million people get infected from hospitals, and more than 13 million died due to these hospitals’ acquired deadly diseases. The market available PPE are though effective against the penetration of pathogens and to kill bacteria but, they are not breathable and active against different viruses. Therefore, there was a great need to develop textiles that are not only effective against bacteria, fungi, and viruses but also are comfortable to the medical personnel and patients. In the present study, waterproof breathable, and biologically active textiles were developed using antiviral and antibacterial nanomaterials. These nanomaterials like TiO₂, ZnO, Cu, and Ag were immobilized at the surface of cotton fabric by using different silane coupling agents and electroless deposition that they retained their functionality even after 30 industrial laundering cycles. Afterwards, the treated fabrics were coated with a waterproof breathable film to prevent the permeation of liquid droplets, any particle or microorganisms greater than 80 nm. The developed cotton fabric was highly active against bacteria and viruses. The good durability of nanomaterials at the cotton surface after several industrial washing cycles makes this fabric an ideal candidate for bioactive textiles used in the medical field.

Keywords: antibacterial, antiviral, cotton, durable

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Authors: Manal Kamel, Sara Maher, Hanan El Baz, Faten Salah, Omar Sayyouh, Zeinab Demerdash

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In the recent COVID 19 pandemic, experts of public health have emphasized testing, tracking infected people, and tracing their contacts as an effective strategy to reduce the spread of the virus. Development of rapid and sensitive diagnostic assays to replace reverse transcription polymerase chain reaction (RT-PCR) is mandatory..Our innovative test strip relying on the application of nanoparticles conjugated to recombinant nanobodies for SARS-COV-2 spike protein (S1) & angiotensin-converting enzyme 2 (that is responsible for the virus entry into host cells) for rapid detection of SARS-COV-2 spike protein (S1) in saliva or sputum specimens. Comparative tests with RT-PCR will be held to estimate the significant effect of using COVID 19 nanobodies for the first time in the development of lateral flow test strip. The SARS-CoV-2 S1 (3 ng of recombinant proteins) was detected by our developed LFIA in saliva specimen of COVID-19 Patients No cross-reaction was detected with Middle East respiratory syndrome coronavirus (MERS-CoV) or SARS- CoV antigens..Our developed system revealed 96 % sensitivity and 100% specificity for saliva samples compared to 89 % and 100% sensitivity and specificity for nasopharyngeal swabs. providing a reliable alternative for the painful and uncomfortable nasopharyngeal swab process and the complexes, time consuming PCR test. An increase in testing compliances to be expected.

Keywords: COVID 19, diagnosis, LFIA, nanobodies, ACE2

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Authors: V. K. Rajaletchumy, S. L. Chia, M. I. Setyawati, M. S. Muthu, S. S. Feng, D. T. Leong

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Triple negative breast cancers (TNBC) can be classified as one of the most aggressive with a high rate of local recurrences and systematic metastases. TNBCs are insensitive to existing hormonal therapy or targeted therapies such as the use of monoclonal antibodies, due to the lack of oestrogen receptor (ER) and progesterone receptor (PR) and the absence of overexpression of human epidermal growth factor receptor 2 (HER2) compared with other types of breast cancers. The absence of targeted therapies for selective delivery of therapeutic agents into tumours, led to the search for druggable targets in TNBC. In this study, we developed a targeted micellar system of cetuximab-conjugated micelles of D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) for targeted delivery of docetaxel as a model anticancer drug for the treatment of TNBCs. We examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. The targeting micelles were found preferentially accumulated in tumours immediately after the administration of the micelles compare to normal tissue. The fluorescence signal gradually increased up to 12 h at the tumour site and sustained for up to 24 h, reflecting the increases in targeted micelles (TPFC) micelles in MDA-MB-231/Luc cells. In comparison, for the non-targeting micelles (TPF), the fluorescence signal was evenly distributed all over the body of the mice. Only a slight increase in fluorescence at the chest area was observed after 24 h post-injection, reflecting the moderate uptake of micelles by the tumour. The successful delivery of docetaxel into tumour by the targeted micelles (TPDC) exhibited a greater degree of tumour growth inhibition than Taxotere® after 15 days of treatment. The ex vivo study has demonstrated that tumours treated with targeting micelles exhibit enhanced cell cycle arrest and attenuated proliferation compared with the control and with those treated non-targeting micelles. Furthermore, the ex vivo investigation revealed that both the targeting and non-targeting micellar formulations shows significant inhibition of cell migration with migration indices reduced by 0.098- and 0.28-fold, respectively, relative to the control. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGF-overexpressing MDA-MB-231 tumours.

Keywords: biodegradable polymers, cancer nanotechnology, drug targeting, molecular biomaterials, nanomedicine

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Authors: R. Tajau, R. Rohani, M. S. Alias, N. H. Mudri, K. A. Abdul Halim, M. H. Harun, N. Mat Isa, R. Che Ismail, S. Muhammad Faisal, M. Talib, M. R. Mohamed Zin

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Bio-based polymeric materials are increasingly used for a variety of applications, including surface coating, drug delivery systems, and tissue engineering. These polymeric materials are ideal for the aforementioned applications because they are derived from natural resources, non-toxic, low-cost, biocompatible, and biodegradable, and have promising thermal and mechanical properties. The nature of hydrocarbon chains, carbon double bonds, and ester bonds allows various sources of oil (edible), such as soy, sunflower, olive, and oil palm, to fine-tune their particular structures in the development of innovative materials. Palm oil can be the most eminent raw material used for manufacturing new and advanced natural polymeric materials involving radiation techniques, such as coating resins, nanoparticles, scaffold, nanotubes, nanocomposites, and lithography for different branches of the industry in countries where oil palm is abundant. The radiation technique is among the most versatile, cost-effective, simple, and effective methods. Crosslinking, reversible addition-fragmentation chain transfer (RAFT), polymerisation, grafting, and degradation are among the radiation mechanisms. Exposure to gamma, EB, UV, or laser irradiation, which are commonly used in the development of polymeric materials, is used in these mechanisms. Therefore, this review focuses on current radiation processing technologies for the development of various radiation-curable bio-based polymeric materials with a promising future in biomedical and industrial applications. The key focus of this review is on radiation curable palm oil-based products, which have been published frequently in recent studies.

Keywords: palm oil, radiation processing, surface coatings, VOC

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Authors: Garima, S. Pushpavanam

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In this work, analysis of an Aqueous two-phase (polymer-salt) system for extraction of sunset yellow dye is carried out. A polymer-salt ATPS i.e.; Polyethylene glycol-600 and anhydrous sodium sulfate is used for the extraction. Conditions are chosen to ensure that the extraction results in a concentration of the dye in one of the phases. The dye has a propensity to come to the Polyethylene glycol-600 phase. This extracted sunset yellow dye is degraded photo catalytically into less harmful components. The cloud point method was used to obtain the binodal curve of ATPS. From the binodal curve, the composition of salt and Polyethylene glycol -600 was chosen such that the volume of Polyethylene glycol-600 rich phase is low. This was selected to concentrate the dye from a dilute solution in a large volume of contaminated solution into a small volume. This pre-concentration step provides a high reaction rate for photo catalytic degradation reaction. Experimentally the dye is extracted from the salt phase to Polyethylene glycol -600 phase in batch extraction. This was found to be very fast and all dye was extracted. The concentration of sunset yellow dye in salt and polymer phase is measured at 482nm by ultraviolet-visible spectrophotometry. The extraction experiment in micro channels under stratified flow is analyzed to determine factors which affect the dye extraction. Focus will be on obtaining slug flow by adding nanoparticles in micro channel. The primary aim is to exploit the fact that slug flow will help improve mass transfer rate from one phase to another through internal circulation in dispersed phase induced by shear.

Keywords: aqueous two phase system, binodal curve, extraction, sunset yellow dye

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Authors: J. Plocek, P. Holec, S. Kubickova, B. Pacakova, I. Matulkova, A. Mantlikova, I. Němec, D. Niznansky, J. Vejpravova

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This article presents summary on preparation and characterization of zinc, copper, cadmium and cobalt chromite nano crystals, embedded in an amorphous silica matrix. The ZnCr2O4/SiO2, CuCr2O4/SiO2, CdCr2O4/SiO2 and CoCr2O4/SiO2 nano composites were prepared by a conventional sol-gel method under acid catalysis. Final heat treatment of the samples was carried out at temperatures in the range of 900–1200 °C to adjust the phase composition and the crystallite size, respectively. The resulting samples were characterized by Powder X-ray diffraction (PXRD), High Resolution Transmission Electron Microscopy (HRTEM), Raman/FTIR spectroscopy and magnetic measurements. Formation of the spinel phase was confirmed in all samples. The average size of the nano crystals was determined from the PXRD data and by direct particle size observation on HRTEM; both results were correlated. The mean particle size (reviewed by HRTEM) was in the range from ~ 4 to 46 nm. The results showed that the sol-gel method can be effectively used for preparation of the spinel chromite nano particles embedded in the silica matrix and the particle size is driven by the type of the cation A2+ in the spinel structure and the temperature of the final heat treatment. Magnetic properties of the nano crystals were found to be just moderately modified in comparison to the bulk phases.

Keywords: sol-gel method, nanocomposites, Rietveld refinement, Raman spectroscopy, Fourier transform infrared spectroscopy, magnetic properties, spinel, chromite

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Authors: Mrinalini Amritkar, Disha Patil, Swapna Kulkarni, Sukratu Barve, Suresh Gosavi

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Micro-mixers play an important role in the lab-on-a-chip applications and micro total analysis systems to acquire the correct level of mixing for any given process. The mixing process can be classified as active or passive according to the use of external energy. Literature of microfluidics reports that most of the work is done on the models of steady laminar flow; however, the study of unsteady laminar flow is an active area of research at present. There are wide applications of this, out of which, we consider nanoparticle synthesis in micro-mixers. In this work, we have developed a model for unsteady flow to study the mixing performance of a passive micro mixer for reactants used for such synthesis. The model is developed in Finite Volume Method (FVM)-based software, OpenFOAM. The model is tested by carrying out the simulations at Re of 0.5. Mixing performance of the micro-mixer is investigated using simulated concentration values of mixed species across the width of the micro-mixer and calculating the variance across a line profile. Experimental validation is done by passing dyes through a Y shape micro-mixer fabricated using polydimethylsiloxane (PDMS) polymer and comparing variances with the simulated ones. Gold nanoparticles are later synthesized through the micro-mixer and collected at two different times leading to significantly different size distributions. These times match with the time scales over which reactant concentrations vary as obtained from simulations. Our simulations could thus be used to create design aids for passive micro-mixers used in nanoparticle synthesis.

Keywords: Lab-on-chip, LOC, micro-mixer, OpenFOAM, PDMS

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Authors: Yasinta Ratna Esti Wulandari, Vivitri Dewi Prasasty, Adrianus Rio, Cindy Geniola

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Mulberry is a plant that widely cultivated around the world, mostly for silk industry. In recent years, the study showed that the mulberry leaves have an anti-diabetic effect which mostly comes from the compound known as 1-deoxynojirimycin (DNJ). DNJ is a very potent α-glucosidase inhibitor. It will decrease the degradation rate of carbohydrates in digestive tract, leading to slower glucose absorption and reducing the post-prandial glucose level significantly. The mulberry leaves also known as the best source of DNJ. Since then, the DNJ in mulberry leaves had received a considerable attention, because of the increased number of diabetic patients and the raise of people awareness to find a more natural cure for diabetic. The DNJ content in mulberry leaves varied depend on the mulberry species, leaf’s age, and the plant’s growth environment. Few of the mulberry varieties that were cultivated in Indonesiaare Morus alba var. kanva-2, M. alba var. multicaulis, M. bombycis var. lembang, and M. cathayana. The lack of data concerning phytochemicals contained in the Indonesian mulberry leaves are restraining their use in the medicinal field. The aim of this study is to fully utilize the use of mulberry leaves cultivated in Indonesia as a medicinal herb in local, national, or global community, by determining the DNJ and other phytochemical contents in them. This study used eight leaf samples which are the young leaves and mature leaves of both Morus alba var. kanva-2, M. alba var. multicaulis, M. bombycis var. lembang, and M. cathayana. The DNJ content was analyzed using reverse phase high performance liquid chromatography (HPLC). The stationary phase was silica C18 column and the mobile phase was acetonitrile:acetic acid 0.1% 1:1 with elution rate 1 mL/min. Prior to HPLC analysis the samples were derivatized with FMOC to ensure the DNJ detectable by VWD detector at 254 nm. Results showed that the DNJ content in samples are ranging from 2.90-0.07 mg DNJ/ g leaves, with the highest content found in M. cathayana mature leaves (2.90 ± 0.57 mg DNJ/g leaves). All of the mature leaf samples also found to contain higher amount of DNJ from their respective young leaf samples. The phytochemicals in leaf samples was tested using qualitative test. Result showed that all of the eight leaf samples contain alkaloids, phenolics, flavonoids, tannins, and terpenes. The presence of this phytochemicals contribute to the therapeutic effect of mulberry leaves. The pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) analysis was also performed to the eight samples to quantitatively determine their phytochemicals content. The pyrolysis temperature was set at 400 °C, with capillary column Phase Rtx-5MS 60 × 0.25 mm ID stationary phase and helium gas mobile phase. Few of the terpenes found are known to have anticancer and antimicrobial properties. From all the results, all of four samples of mulberry leaves which are cultivated in Indonesia contain DNJ and various phytochemicals like alkaloids, phenolics, flavonoids, tannins, and terpenes which are beneficial to our health.

Keywords: Morus, 1-deoxynojirimycin, HPLC, Py-GC-MS

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Authors: Priya Ruban, Thirunavoukkarasu Manikkannan, Sakthivel Ramasamy

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Sulfide is one of the major pollutants of tannery effluent which is mainly generated during the process of unhairing. Recovery of Hydrogen green fuel from sulfide wastewater using photocatalysis is a ‘Cleaner Production Method’, since renewable solar energy is utilized. It has triple advantages of the generation of H2, waste minimization and odor or pollution control. Designing of safe and green photocatalysts and developing suitable solar photoreactor is important for promoting this technology to large-scale application. In this study, green photocatalyst i.e., spinach derived carbon dots (SCDs 5 wt % and 10 wt %)/TiO2 nanocomposite was synthesized for generation of H2 from sulfide wastewater using lab-scale solar photocatalytic reactor. The physical characterization of the synthesized solar light responsive nanocomposites were studied by using DRS UV-Vis, XRD, FTIR and FESEM analysis. The absorption edge of TiO2 nanoparticles is extended to visible region by the incorporation of SCDs, which was used for converting noxious pollutant sulfide into eco-friendly solar fuel H2. The SCDs (10 wt%)-TiO2 nanocomposite exhibits enhanced photocatalytic hydrogen production i.e. ~27 mL of H2 (180 min) from simulated sulfide wastewater under LED visible light irradiation which is higher as compared to SCDs. The enhancement in the photocatalytic generation of H2 is attributed to combining of SCDs which increased the charge mobility. This work may provide new insights to usage of naturally available and cheap materials to design novel nanocomposite as a visible light active photocatalyst for the generation of H2 from sulfide containing wastewater.

Keywords: carbon dots, hydrogen fuel, hydrogen sulfide, photocatalysis, sulfide wastewater

Procedia PDF Downloads 357

Authors: P. G. Siddheshwar, T. N. Sakshath

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In the paper we make linear and non-linear stability analyses of Rayleigh-Bénard convection of a Newtonian nanoliquid in a rotating medium (called as Rayleigh-Bénard-Taylor convection). Rigid-rigid isothermal boundaries are considered for investigation. Khanafer-Vafai-Lightstone single phase model is used for studying instabilities in nanoliquids. Various thermophysical properties of nanoliquid are obtained using phenomenological laws and mixture theory. The eigen boundary value problem is solved for the Rayleigh number using an analytical method by considering trigonometric eigen functions. We observe that the critical nanoliquid Rayleigh number is less than that of the base liquid. Thus the onset of convection is advanced due to the addition of nanoparticles. So, increase in volume fraction leads to advanced onset and thereby increase in heat transport. The amplitudes of convective modes required for estimating the heat transport are determined analytically. The tri-modal standard Lorenz model is derived for the steady state assuming small scale convective motions. The effect of rotation on the onset of convection and on heat transport is investigated and depicted graphically. It is observed that the onset of convection is delayed due to rotation and hence leads to decrease in heat transport. Hence, rotation has a stabilizing effect on the system. This is due to the fact that the energy of the system is used to create the component V. We observe that the amount of heat transport is less in the case of rigid-rigid isothermal boundaries compared to free-free isothermal boundaries.

Keywords: nanoliquid, rigid-rigid, rotation, single phase

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Authors: Yong Zhang

Abstract:

Light has proven to be useful in a wide range of biomedical applications such as fluorescence imaging, photoacoustic imaging, optogenetics, photodynamic therapy, photothermal therapy, and light controlled drug/gene delivery. Taking photodynamic therapy (PDT) as an example, PDT has been proven clinically effective in early lung cancer, bladder cancer, head, and neck cancer and is the primary treatment for skin cancer as well. However, clinical use of PDT is severely constrained by the low penetration depth of visible light through thick tissue, limiting its use to target regions only a few millimeters deep. One way to enhance the range is to use invisible near-infrared (NIR) light within the optical window (700–1100nm) for biological tissues, extending the depth up to 1cm with no observable damage to the intervening tissue. We have demonstrated use of NIR-to-visible upconversion fluorescent nanoparticles (UCNPs), emitting visible fluorescence when excited by a NIR light at 980nm, as a nanotransducer for PDT to convert deep tissue-penetrating NIR light to visible light suitable for activating photosensitizers. The unique optical properties of UCNPs enable the upconversion wavelength to be tuned and matched to the activation absorption wavelength of the photosensitizer. At depths beyond 1cm, however, tissue remains inaccessible to light even within the NIR window, and this critical depth limitation renders existing phototherapy ineffective against most deep-seated cancers. We have demonstrated some new treatment modalities for deep-seated cancers based on UCNP hydrogel implants and miniaturized, wirelessly powered optoelectronic devices for light delivery to deep tissues.

Keywords: upconversion, fluorescent, nanoparticle, bioimaging, photodynamic therapy

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Authors: Emil F. Khisamutdinov

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Development of functional materials undergoing structural transformations in response to an external stimulus such as environmental changes (pH, temperature, etc.), the presence of particular proteins, or short oligonucleotides are of great interest for a variety of applications ranging from medicine to electronics. The dynamic operations of most nucleic acid (NA) devices, including circuits, nano-machines, and biosensors, rely on networks of NA strand displacement processes in which an external or stimulus strand displaces a target strand from a DNA or RNA duplex. The rate of strand displacement can be greatly increased by the use of “toeholds,” single-stranded regions of the target complex to which the invading strand can bind to initiate the reaction, forming additional base pairs that provide a thermodynamic driving force for transformation. Herein, we developed a highly robust nanoparticle shape transition, sequentially transforming DNA polygons from one shape to another using the toehold-mediated DNA strand displacement technique. The shape transformation was confirmed by agarose gel electrophoresis and atomic force microscopy. Furthermore, we demonstrate that our approach is applicable for RNA shape transformation from triangle to square, which can be detected by fluorescence emission from malachite green binding RNA aptamer. Using gel-shift and fluorescence assays, we demonstrated efficient transformation occurs at isothermal conditions (37°C) that can be implemented within living cells as reporter molecules. This work is intended to provide a simple, cost-effective, and straightforward model for the development of biosensors and regulatory devices in nucleic acid nanotechnology.

Keywords: RNA nanotechnology, bionanotechnology, toehold mediated DNA switch, RNA split fluorogenic aptamers

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Authors: Banu Hatice Gürcüm, Pınar Arslan, Mahmut Yalçın

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From the oldest production methods with yarns used to weave, knit, braid and knot to the newest production methods with fibres used to stitch, bond or structures of innovative technologies, laminates, nanoparticles, composites or 3D printing systems, textile industry advanced through materials, processes and context mostly within the last five decades. The creative momentum of fabric like 3D printed structures have come to the point of transforming as for the newest form of textile applications. Moreover, pioneering studies on the applications of 3D Printing Technology and Additive Manufacturing have been focusing on fashion and apparel sector from the last two decades beginning with fashion designers. After the advent of chain-mail like structures and flexible micro or meso structures created by SLS rapid manufacturing a more textile-like behavior is achieved. Thus, the primary aim of this paper is to discuss the most important properties of traditional fabrics that are to be expected of future fabrics. For this reason, this study deals primarily with the physical properties like softness, hand, flexibility, drapability and wearability of 3D Printed structures necessary to identify the possible ways in which it can be used instead of contemporary textile structures, namely knitted and woven fabrics. The aim of this study is to compare the physical properties of 3D printed fabrics regarding different rapid manufacturing methods (FDM and SLS). The implemented method was Material Driven Design (MDD), which comprise the use of innovative materials according to the production techniques such as 3D printing system. As a result, advanced textile processes and materials enable to the creation of new types of fabric structures and rapid solutions in the field of textiles and 3D fabrics on the other hand, are to be used in this regard.

Keywords: 3D printing technology, FDM, SLS, textile structure

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Authors: Samaneh Farokhirad, Fatemeh Ahmadpoor

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Biological membranes are constantly in contact with various filamentous soft nanostructures that either reside on their surface or are being transported between the cell and its environment. In particular, viral infections are determined by the interaction of viruses (such as filovirus) with cell membranes, membrane protein organization (such as cytoskeletal proteins and actin filament bundles) has been proposed to influence the mechanical properties of lipid membranes, and the adhesion of filamentous nanoparticles influence their delivery yield into target cells or tissues. The goal of this research is to integrate the rapidly increasing but still fragmented experimental observations on the adhesion and self-assembly of nanofilaments (including filoviruses, actin filaments, as well as natural and synthetic nanofilaments) on cell membranes into a general, rigorous, and unified knowledge framework. The global outbreak of the coronavirus disease in 2020, which has persisted for over three years, highlights the crucial role that nanofilamentbased delivery systems play in human health. This work will unravel the role of a unique property of all cell membranes, namely flexoelectricity, and the significance of nanofilaments’ flexibility in the adhesion and self-assembly of nanofilaments on cell membranes. This will be achieved utilizing a set of continuum mechanics, statistical mechanics, and molecular dynamics and Monte Carlo simulations. The findings will help address the societal needs to understand biophysical principles that govern the attachment of filoviruses and flexible nanofilaments onto the living cells and provide guidance on the development of nanofilament-based vaccines for a range of diseases, including infectious diseases and cancer.

Keywords: virus nanofilaments, cell mechanics, computational biophysics, statistical mechanics

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Authors: Ayat Adnan Atwah, Muhammad A. Khan

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Self-cleaning surfaces are getting significant attention in industrial fields. Especially for textile fabrics, it is observed that self-cleaning textile fabric surfaces are created by manipulating the surface features with the help of coatings and nanoparticles, which are considered costly and far more complicated. However, controlling the fabrication parameters of textile fabrics at the microscopic level by exploring the potential for self-cleaning has not been addressed. This study aimed to establish the context of self-cleaning textile fabrics by controlling the fabrication parameters of the textile fabric at the microscopic level. Therefore, 3D-printed textile fabrics were fabricated using the low-cost fused filament fabrication (FFF) technique. The printing parameters, such as orientation angle (O), layer height (LH), and extruder width (EW), were used to control the microscopic features of the printed fabrics. The combination of three printing parameters was created to provide the best self-cleaning textile fabric surface: (LH) (0.15, 0.13, 0.10 mm) and (EW) (0.5, 0.4, 0.3 mm) along with two different (O) of (45º and 90º). Three different thermoplastic flexible filament materials were used: (TPU 98A), (TPE felaflex), and (TPC flex45). The printing parameters were optimised to get the optimum self-cleaning ability of the printed specimens. Furthermore, the impact of these characteristics on mechanical strength at the fabric-woven structure level was investigated. The study revealed that the printing parameters significantly affect the self-cleaning properties after adjusting the selected combination of layer height, extruder width, and printing orientation. A linear regression model was effectively developed to demonstrate the association between 3D printing parameters (layer height, extruder width, and orientation). According to the experimental results, (TPE felaflex) has a better self-cleaning ability than the other two materials.

Keywords: 3D printing, self-cleaning fabric, microscopic features, printing parameters, fabrication

Procedia PDF Downloads 55

Authors: Yagahira E. Castro-Sesquen, Robert H. Gilman, Carolina Mejia, Daniel E. Clark, Jeong Choi, Melissa J. Reimer-Mcatee, Rocio Castro, Jorge Flores, Edward Valencia-Ayala, Faustino Torrico, Ricardo Castillo-Neyra, Lance Liotta, Caryn Bern, Alessandra Luchini

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Early diagnosis of reactivation of Chagas disease in HIV patients could be lifesaving; however, in Latin American the diagnosis is performed by detection of parasitemia by microscopy which lacks sensitivity. To evaluate if levels of T. cruzi antigens in urine determined by Chunap (Chagas urine nanoparticle test) are correlated with parasitemia levels in T. cruzi/HIV co-infected patients. T. cruzi antigens in urine of HIV patients (N=55: 31 T. cruzi infected and 24 T. cruzi serology negative) were concentrated using hydrogel particles and quantified by Western Blot and a calibration curve. The percentage of Chagas positive patients determined by Chunap compared to blood microscopy, qPCR, and ELISA was 100% (6/6), 95% (18/19) and 74% (23/31), respectively. Chunap specificity was 91.7%. Linear regression analysis demonstrated a direct relationship between parasitemia levels (determined by qPCR) and urine T. cruzi antigen concentrations (p<0.001). A cut-off of > 105 pg was chosen to determine patients with reactivation of Chagas disease (6/6). Urine antigen concentration was significantly higher among patients with CD4+ lymphocyte counts below 200/mL (p=0.045). Chunap shows potential for early detection of reactivation and with appropriate adaptation can be used for monitoring Chagas disease status in T. cruzi/HIV co-infected patients.

Keywords: antigenuria, Chagas disease, Chunap, nanoparticles, parasitemia, poly N-isopropylacrylamide (NIPAm)/trypan blue particles (polyNIPAm/TB), reactivation of Chagas disease.

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Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

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Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

Procedia PDF Downloads 184