A comparative study was conducted for the machining of two α/β titanium alloys, namely Ti-6Al-4V (Ti64) and Ti-6Al-7Nb (Ti67), using wire electric discharge machining (WEDM). The influence of cutting ...speed and cutting mode on the machined surfaces in terms of surface roughness (Ra), recast layer (RL), and micro-hardness have been evaluated. Rough cut (RC) mode at a cutting speed of 50 µm/s resulted in thermal damage; Ra was equal to 5.68 ± 0.44 and 4.52 ± 0.35 µm for Ti64 and Ti67, respectively. Trim-cut mode using seven cuts (TRC-VII) at the same speed decreased the Ra to 1.02 ± 0.20 µm for Ti64 and 0.92 ± 0.10 µm for Ti67. At 100 µm/s, Ra reduced from 2.34 ± 0.28 µm to 0.88 ± 0.12 µm (Ti64), and from 1.42 ± 0.15 µm to 0.90 ± 0.08µm (Ti67) upon changing from TRC-III to TRC-VII. Furthermore, a thick recast layer of 30 ± 0.93 µm for Ti64 and 14 ± 0.68 µm for Ti67 was produced using the rough mode, while TRC-III and TRC-VII modes produced layers of 12 ± 1.31 µm and 5 ± 0.72 µm for Ti64 and Ti67, respectively. Moreover, rough cut and trim cut modes of WEDM played a significant role in promoting the surface hardness of Ti64 and Ti67. By employing the Response Surface Methodology, it was found that the machining mode followed by cutting speed and the interaction between them are the most influential parameters on surface roughness. Finally, mathematical models correlating machining parameters to surface roughness were successfully developed. The results strongly promote the trim-cut mode of WEDM as a promising machining route for two-phase titanium alloys.
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Using the internal transcribed spacer (ITS) region for identification, three strains of
were identified and designated AUMC 15760, AUMC 15762, and AUMC 15763 for the Assiut University Mycological ...Centre culture collection. The ability of the three strains to manufacture lovastatin in solid-state fermentation (SSF) using wheat bran was assessed using gas chromatography-mass spectroscopy (GC-MS). The most potent strain was strain AUMC 15760, which was chosen to ferment nine types of lignocellulosic waste (barley bran, bean hay, date palm leaves, flax seeds, orange peels, rice straw, soy bean, sugarcane bagasse, and wheat bran), with sugarcane bagasse turning out to be the best substrate. After 10 days at pH 6.0 at 25 °C using sodium nitrate as the nitrogen source and a moisture content of 70%, the lovastatin output reached its maximum quantity (18.2 mg/g substrate). The medication was produced in lactone form as a white powder in its purest form using column chromatography. In-depth spectroscopy examination, including
H,
C-NMR, HR-ESI-MS, optical density, and LC-MS/MS analysis, as well as a comparison of the physical and spectroscopic data with published data, were used to identify the medication. At an IC
of 69.536 ± 5.73 µM, the purified lovastatin displayed DPPH activity.
and
had MICs of 1.25 mg/mL, whereas
and
had MICs of 2.5 mg/mL and 5.0 mg/mL, respectively, against pure lovastatin. As a component of sustainable development, this study offers a green (environmentally friendly) method for using sugarcane bagasse waste to produce valuable chemicals and value-added commodities.
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IL-15 has shown preclinical activity by enhancing the functional maturation of natural killer (NK) cells. Clinical evaluation of the potential anticancer activity of most cytokines, including IL-15, ...has been limited by low tolerability and rapid
clearance. Efbalropendekin Alfa (XmAb24306) is a soluble IL15/IL15-receptor alpha heterodimer complex fused to a half-life extended Fc domain (IL15/IL15Rα-Fc), engineered with mutations to reduce IL-15 affinity for CD122. Reduced affinity drives lower potency, leading to prolonged pharmacodynamic response in cynomolgus monkeys. We show that
, human NK cells treated with XmAb24306 demonstrate enhanced cytotoxicity against various tumor cell lines. XmAb24306-treated NK cells also exhibit enhanced killing of 3D colorectal cancer spheroids. Daratumumab (dara), a monoclonal antibody (mAb) that targets CD38 results in antibody-dependent cellular cytotoxicity (ADCC) of both multiple myeloma (MM) cells and NK cells. Addition of XmAb24306 increases dara-mediated NK cell ADCC against various MM cell lines
. Because NK cells express CD38, XmAb24306 increases dara-mediated NK cell fratricide, but overall does not negatively impact the ADCC activity against a MM cell line likely due to increased NK cell activity of the surviving cells. These data show that XmAb24306 increases direct and ADCC-mediated human NK cell cytotoxicity
.
Natural products have been extensively used for treating a wide variety of disorders. In recent times, Brucine (BRU) as one of the natural medications extracted from seeds of nux vomica, was ...investigated for its anticancer activity. As far as we know, this is the first study on BRU anticancer activity against skin cancer. Thus, the rational of this work was implemented to develop, optimize and characterize the anticancer activity of BRU loaded ethosomal gel. Basically, thin film hydration method was used to formulate BRU ethosomal preparations, by means of Central composite design (CCD), which were operated to construct (32) factorial design. Two independent variables were designated (phospholipid percentage and ethanol percentage) with three responses (vesicular size, encapsulation efficiency and flux). Based on the desirability function, one formula was selected and incorporated into HPMC gel base to develop BRU loaded ethosomal gel. The fabricated gel was assessed for all physical characterization. In-vitro release investigation, ex-vivo permeation and MTT calorimetric assay were performed. BRU loaded ethosomal gel exhibited acceptable values for the characterization parameters which stand proper for topical application. In-vitro release investigation was efficiently prolonged for 6 h. The flux from BRU loaded ethosome was enhanced screening optimum SSTF value. Finally, in-vitro cytotoxicity study proved that BRU loaded ethosomal gel significantly improved the anticancer activity of the drug against A375 human melanoma cell lines. Substantially, the investigation proposed a strong motivation for further study of the lately developed BRU loaded ethosomal gel as a prospective therapeutic strategy for melanoma treatment.
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One of the current challenges is to secure wheat crop production to meet the increasing global food demand and to face the increase in its purchasing power. Therefore, the current study aimed to ...exploit a new synthesized nanocomposite to enhance wheat growth under both normal and drought regime. The effectiveness of this nanocomposite in improving the microbiological quality of irrigation water and inhibiting the snail's growth was also assessed.
Upon the employed one-step synthesis process, a spherical Fe/Cu/P nanocomposite was obtained with a mean particle size of 4.35 ± 1.524 nm. Cu
, Fe
, and P
were detected in the dried nanocomposite at 14.533 ± 0.176, 5.200 ± 0.208, and 34.167 ± 0.203 mg/ml concentration, respectively. This nanocomposite was found to exert antibacterial activity against Escherichia coli and Salmonella typhi. It caused good inhibition percent against Fusarium oxysporum (43.5 ± 1.47%) and reduced both its germination rate and germination efficiency. The lethal concentration 50 (LC
of this nanocomposite against Lanistes carinatus snails was 76 ppm. The treated snails showed disturbance in their feeding habit and reached the prevention state. Significant histological changes were observed in snail digestive tract and male and female gonads. Drought stress on wheat's growth was mitigated in response to 100 and 300 ppm treatments. An increase in all assessed growth parameters was reported, mainly in the case of 100 ppm treatment under both standard and drought regimes. Compared to control plants, this stimulative effect was accompanied by a 2.12-fold rise in mitotic index and a 3.2-fold increase in total chromosomal abnormalities.
The finding of the current study could be employed to mitigate the effect of drought stress on wheat growth and to enhance the microbiological quality of irrigation water. This is due to the increased efficacy of the newly synthesized Fe/Cu/P nanocomposite against bacteria, fungi, and snails. This methodology exhibits potential for promoting sustainable wheat growth and water resource conservation.
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Geraniol, a natural monoterpene, is an essential oil component of many plants. Methotrexate is an anti-metabolite drug, used for cancer and autoimmune conditions; however, clinical uses of ...methotrexate are limited by its concomitant renal injury. This study investigated the efficacy of geraniol to prevent methotrexate-induced acute kidney injury and via scrutinizing the Keap1/Nrf2/HO-1, P38MAPK/NF-κB and Bax/Bcl2/caspase-3 and -9 pathways.
Male Wister rats were allocated into five groups: control, geraniol (orally), methotrexate (IP), methotrexate and geraniol (100 and 200 mg/kg).
Geraniol effectively reduced the serum levels of creatinine, urea and Kim-1 with an increase in the serum level of albumin when compared to the methotrexate-treated group. Geraniol reduced Keap1, escalated Nrf2 and HO-1, enhanced the antioxidant parameters GSH, SOD, CAT and GSHPx and reduced MDA and NO. Geraniol decreased renal P38 MAPK and NF-κB and ameliorated the inflammatory mediators TNF-α, IL-1β, IL-6 and IL-10. Geraniol negatively regulated the apoptotic mediators Bax and caspase-3 and -9 and increased Bcl2. All the biochemical findings were supported by the alleviation of histopathological changes in kidney tissues.
The current findings support that co-administration of geraniol with methotrexate may attenuate methotrexate-induced acute kidney injury.
An experimental work were conducted for investigating cylinder pressure, performance parameters, heat release, specific heat ratio and duration of combustion for multi cylinder spark ignition engine ...(SIE). Ccylinder pressure was measured for gasoline, kerosene and Liquefied Petroleum Gases (LPG) separately as a fuel for SIE. Fast Fourier Transformations (FFT) was used to cylinder pressure data transform from time domain into frequency domain to develop empirical correlation for calculating cylinder pressures at different engine speeds and different fuels. In addition, Inverse Fast Fourier Transformations (IFFT) was used to cylinder pressure reconstruct into time domain. The results gave good agreement between the measured cylinder pressure and the reconstructed cylinder pressure in time domain with different engine speeds and different fuels. The measured cylinder pressure and hydraulic dynamotor were the sours of data for calculating engine performance parameters. First law of thermodynamics and single zone heat release model with temperature dependant specific heat ratio γ(T) were the main tools for calculating heat release and heat transfer to cylinder walls. Third order empirical correlation for calculating γ(T) was one of the main gains of the present study. The correlation gave good agreement with other researchers with wide temperatures range. For kerosene, cylinder pressure is higher than for gasoline and LPG due to high volumetric efficiency where kerosene density (mass/volume ratio) is higher than gasoline and LPG. In addition, kerosene heating value is higher than gasoline that contributes in heat release rate and pressure increases. Duration of combustion for different engine speeds was determined using four different methods: (I) Mass fuel burnt, (II) Entropy change, (III) Temperature dependant specific heat ratio γ(T), and (IV) Logarithmic scale of (P&V). The duration of combustion for kerosene is smaller than for gasoline and LPG due to high heat release rate. Cylinder pressure measuring technique is a useful tool for understanding and analyzing the combustion characteristics and determining reliable statistical data that cannot measure directly. The present work contributes in determining combustion characteristics, development and optimal operating conditions of SIE for different fuels.
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Nanoemulsion is one of the potential drug delivery strategies used in topical ocular therapy. The purpose of this study was to design and optimize a nanoemulsion-based system to improve therapeutic ...efficacy of moxifloxacin in ophthalmic delivery. Moxifloxacin nanoemulsions were prepared by testing their solubility in oil, surfactants, and cosurfactants. A pseudoternary phase diagram was constructed by titration technique and nanoemulsions were obtained with four component mixtures of Tween 80, Soluphor
P, ethyl oleate and water. An experiment with simplex lattice design was conducted to assess the influence of formulation parameters in seven nanoemulsion formulations (MM1-MM7) containing moxifloxacin. Physicochemical characteristics and in vitro release of MM1-MM7 were examined and optimized formulation (MM3) was further evaluated for ex vivo permeation, antimicrobial activity, ocular irritation and stability. Drug pharmacokinetics in rabbit aqueous humor was assessed for MM3 and compared with conventional commercial eye drop formulation (control). MM3 exhibited complete drug release in 3 h by Higuchi diffusion controlled mechanism. Corneal steady state flux of MM3 (~32.01 µg/cm
/h) and control (~31.53 µg/cm
/h) were comparable. Ocular irritation study indicated good tolerance of MM3 and its safety for ophthalmic use. No significant changes were observed in the physicochemical properties of MM3 when stored in the refrigerator for 3 months. The greater aqueous humor concentration (
; 555.73 ± 133.34 ng/mL) and delayed
value (2 h) observed in MM3 suggest a reduced dosing frequency and increased therapeutic efficacy relative to control. The area under the aqueous humor concentration versus time curve (
) of MM3 (1859.76 ± 424.51 ng·h/mL) was ~2 fold higher (p < 0.0005) than the control, suggesting a significant improvement in aqueous humor bioavailability. Our findings suggest that optimized nanoemulsion (MM3) enhanced the therapeutic effect of moxifloxacin and can therefore be used as a safe and effective delivery vehicle for ophthalmic therapy.
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The treatment of central nervous system (CNS) disorders always remains a challenge for the researchers. The presence of various physiological barriers, primarily the blood-brain barrier (BBB) limits ...the accessibility of the brain and hinders the efficacy of various drug therapies. Hence, drug targeting to the brain, particularly to the diseased cells by circumventing the physiological barriers is essential to develop a promising therapy for the treatment of brain disorders. Presently, the investigations emphasize the role of different nanocarrier systems or surface modified target specific novel carrier system to improve the efficiency and reduce the side effects of the brain therapeutics. Such approaches supposed to circumvent the BBB or have the ability to cross the barrier function and thus increases the drug concentration in the brain. Although the efficacy of novel carrier system depends upon various physiological factors like active efflux transport, protein corona of the brain, stability, and toxicity of the nanocarrier, physicochemical properties, patient-related factors and many more. Hence, to develop a promising carrier system, it is essential to understand the physiology of the brain and BBB and also the other associated factors. Along with this, some alternative route like direct nose-to-brain drug delivery can also offer a better means to access the brain without exposure of the BBB. In this review, we have discussed the role of various physiological barriers including the BBB and blood-cerebrospinal fluid barrier (BCSFB) on the drug therapy and the mechanism of drug transport across the BBB. Further, we discussed different novel strategies for brain targeting of drug including, polymeric nanoparticles, lipidic nanoparticles, inorganic nanoparticles, liposomes, nanogels, nanoemulsions, dendrimers, quantum dots, etc. along with the intranasal drug delivery to the brain. We have also illustrated various factors affecting the drug targeting efficiency of the developed novel carrier system.
In this study, Poly-o-toluidine sulfochromate (POTSC) nancomposite was synthesised for adsorption of Cu(II) from aqueous solutions. The structure of POTSC nanocomposites was characterised by FTIR, ...XRD, SEM, EDX, and TG-DTA techniques. The calculated average crystallite size of OTS and POTSC was 15 and 24 nm respectively. The effects of various parameters such as pH, adsorbent weight, time, and initial Cu(II) concentration on the absorption capacity have been studied. Results showed that the adsorption maximum occurs at pH 5 and adsorption equilibrium was achieved in 30 min. The adsorption capacity of Cu(II) was found to be 30.3 mg/g and kinetic modelling was used to described the adsorption mechanism of Cu(II). The isotherm study reveals that the adsorption data provided by the Langmuir model is stronger than that of Freundlich. The adsorption efficiencies of Cu (II), Zn(II), Ni(II), Ga(II), and Cd(II) on POTSC nanocomposite were 77, 7, 22.7, 2, and 2.8% respectively, which implied that POTSC nanocomposite is good selectivity for Cu (II) than other cations. POTSC nanocomposite may be used to separate copper radionuclides from the irradiated targets.
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