Explore the vast range of titles available.

Drought presents a major risk to wheat growth and productivity under changing climates. During the last few years, various morphological and physiological approaches were used to overcome drought stress-associated problems. Cultivation of tolerant wheat cultivars can serve as a sustainable choice to raise wheat yield under water stress. Herein, field trials were carried out at the experimental farm of Ismailia Agricultural Research Station, Egypt, in two successive growing seasons (2020/2021 and 2021/2022) to investigate the response of four Egyptian bread wheat cultivars (Misr 1, Misr 3, Giza 171, and Sakha 95) to drought stress according to morpho-physiological characteristics, yield, and stress indices. Irrigation treatments and cultivars were assigned to the main and sub-plots, consequently, in a split-plot design with three replicates. The findings revealed that in both the first and second seasons, drought drastically revoked growth vigor of shoot, growth vigor of flag leaf, relative water content (%), membrane stability index (%), photosynthetic pigments, heading (days), maturity (days), as well as yield and yield attributes: spike length, number of spikes/m 2 , spike weight, grain number/spike, 100-kernel weight, grain yield/m 2 , straw yield/m 2 , biological yield/m 2 , and harvest index of all four wheat cultivars. Conversely, drought caused a marked increase in saturation water deficit (%), carotenoids content, and NKP uptake of all four wheat cultivars in both study seasons. The current study found that all four of the wheat cultivars were drought-tolerant plants. These cultivars exhibited similar drought-tolerant behaviors, which included decreased loss in relative water content, membrane stability, and photosynthetic pigment levels, consequently reducing wheat grain yield loss under water stress. Additionally, the drought tolerance indices of Sakha 95 > Giza 171 > Misr 1 > Misr 3 were revealed by the stress sensitivity index (SSI), mean productivity (MP), stress tolerance index (STI), and yield stability index (YSI). In conclusion, Misr 3 was the least tolerant wheat cultivar and Sakha 95 was the most tolerant. These results can be applied to breeding programs by plant breeders.

Axitinib is a second-generation tyrosine kinase inhibitor that works by selectively inhibiting vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3). Through this mechanism of action, axitinib blocks angiogenesis, tumor growth and metastases and therefor it shows significant promise as a chemotherapeutic agent for various types of cancer. Nevertheless, the clinical efficacy of this substance is hindered by its restricted solubility in water and inadequate stability. To address these challenges, we developed spanlastics with polyethylene glycol (PEG) to improve the efficacy and stability of axitinib against breast and ovarian tumor malignancies in a targeted manner. Moreover, the study conducts a thorough examination of the interactions between the ligand Axitinib alone or after coating with PEG and a diverse array of protein types in breast (Dopamine, VEGFR) and ovarian cancer (EGFR, BCL-xL). The fabrication of axitinib- spanlastics was achieved through a thin-film hydration method. The evaluation of the impact of formulation factors on the features of nanovesicles was conducted using the I- optimal design. Subsequently, the optimum formulation was calculated. The optimal formulation was coated with polyethylene glycol (axitinib-PEG-spanlastics). An in vitro assessment was computed to evaluate the efficiency of the optimized axitinib-PEG-spanlastics against the MCF-7 breast cancer cell line and the OV-2774 ovarian cancer cell line. The optimized axitinib-PEG-spanlastics formulation exhibited a diameter of 563.42 ± 8.63 nm, accompanied by a zeta potential of −46.44 ± 0.09 mV. The formulation demonstrated an 84.32 ± 3.64% entrapment percent and a cumulative release of 73.58 ± 3.37% during a 4-hour period. The results obtained from the WST-1 assay showed a significant decrease in the percentage of cell survival, reaching 50% at a concentration of 0.68 µM for the PEG-spanlastics. In contrast, the axitinib free drug suspension exhibited 50% cell survival at a concentration of 1.1 µM in the breast cancer (MCF-7) cell line. In MCF-7 cells, the percentage of apoptotic cells generated by axitinib-PEG-spanlastics compared to the free drug suspension was 70.76 ± 4.971% vs. 32.6 ± 1.803%, while in OV-2774 cells, it was 43.55 ± 4.243% vs. 24.44 ± 4.950%. These results propose that Axitinib-PEG-spanlastics have the potential to be a successful nanoplatform for targeting breast and ovarian cancer and effectively managing tumors.

The oral delivery of diclofenac sodium (DNa), a non-steroidal analgesic, anti-inflammatory drug, is associated with various gastrointestinal side effects. The aim of the research was to appraise the potential of transdermal delivery of DNa using bilosomes as a vesicular carrier (BSVC) in inflamed paw edema. DNa-BSVCs were elaborated using a thin-film hydration technique and optimized using a 31.22 multilevel categoric design with Design Expert® software 10 software (Stat-Ease, Inc., Minneapolis, MI, USA). The effect of formulation variables on the physicochemical properties of BSVC, as well as the optimal formulation selection, was investigated. The BSVCs were evaluated for various parameters including entrapment efficiency (EE%), vesicle size (VS), zeta potential (ZP) and permeation studies. The optimized BSVC was characterized for in vitro release, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and incorporated into hydrogel base. The optimized DNa-BSVC gel effectiveness was assessed in vivo using carrageenan-induced paw edema animal model via cyclooxygenase 2 (COX-2), interleukin 6 (IL-6), Hemooxygenase 1 (HO-1) and nuclear factor-erythroid factor2-related factor 2 (Nfr-2) that potentiate anti-inflammatory and anti-oxidant activity coupled with histopathological investigation. The resulting vesicles presented VS from 120.4 ± 0.65 to 780.4 ± 0.99 nm, EE% from 61.7 ± 3.44 to 93.2 ± 2.21%, ZP from −23.8 ± 2.65 to −82.1 ± 12.63 mV and permeation from 582.9 ± 32.14 to 1350.2 ± 45.41 µg/cm2. The optimized BSVCs were nano-scaled spherical vesicles with non-overlapped bands of their constituents in the FTIR. Optimized formulation has superior skin permeability ex vivo approximately 2.5 times greater than DNa solution. Furthermore, histological investigation discovered that the formed BSVC had no skin irritating properties. It was found that DNa-BSVC gel suppressed changes in oxidative inflammatory mediators (COX-2), IL-6 and consequently enhanced Nrf2 and HO-1 levels. Moreover, reduction of percent of paw edema by about three-folds confirmed histopathological alterations. The results revealed that the optimized DNa-BSVC could be a promising transdermal drug delivery system to boost anti-inflammatory efficacy of DNa by enhancing the skin permeation of DNa and suppressing the inflammation of rat paw edema.

Atherosclerosis is an inflammatory disease characterized by the accumulation of arterial plaque. Diabetes mellitus stands out as a major risk factor for atherosclerosis. Candesartan is a potent angiotensin II receptor antagonist that enhances arterial blood flow and reduces insulin resistance. However, oral candesartan has limited activity because of its low bioavailability, water solubility, hepatic first-pass degradation, and efficacy. The current study aims to develop nasal candesartan-loaded invasome (CLI) drops to improve candesartan’s permeation, release, and bioavailability as a potential treatment for diabetes-associated atherosclerosis. Design expert software was used to prepare various CLI formulations to determine the impact of the concentrations of ethanol, cineole, and phospholipid. The desirability index was used to estimate the optimized formulation composition to maximize entrapment efficiency and minimize vesicle size. The optimized formulation had a 1% ethanol concentration, a 1.5% cineole concentration, and a 2.32% phospholipid concentration. The selected optimized formulation was then tested in a rat model of diabetes and atherosclerosis to evaluate its activity. The results showed that nasal CLI drops significantly raised serum HDL levels by a ratio of 1.42 and lowered serum glucose, cholesterol, triglycerides, LDL, and VLDL levels by 69.70%, 72.22%, 36.52%, 58.0%, and 65.31%, respectively, compared with diabetic atherosclerotic rats, throwing an insight on the potential for promising anti-diabetic and anti-atherosclerotic activities. Additionally, atherosclerotic lesions were improved in rats treated with CLI, as shown in histopathology. In conclusion, the results of this investigation showed that treatment with nasal CSN-loaded invasome formulation drops prevented the initiation and progression of diabetes-associated atherosclerosis. Graphical Abstract

The aerodynamic characteristics of airplanes (i.e., coefficients and derivatives) are essential for the airplane design and optimization process. Generally, accurate calculations of these characteristics are complex and time-consuming. However, the level of accuracy can be adjusted depending on the design phase, problem complexity, and available time for analysis. Thus, diverse tools ranging from simple analytical methods to complex numerical simulations are used to calculate these characteristics during different design steps. This paper presents an efficient tool to expedite the calculation of the aerodynamic characteristics of airplanes with acceptable accuracy based on a combination of analytical and empirical approaches. The goal is to develop a a program tool (AeroMech) that can be used during the airplane preliminary design steps to rapidly assess a large number of alternative configurations and select the best ones for further detailed analysis. For this, enormous empirical relations that are typically represented in charts are digitized and implemented in the developed tool together with the analytical-empirical equations to facilitate and speed up the calculations. Cessna-182 and Cessna-310 airplanes are selected as two case-studies to verify the developed tool against the most common tools such as Digital DATCOM and XFLR5. Finally, the developed tool is partially validated with the available published experimental data for the case-study airplanes. The results show that the tool is able to predict the aerodynamic characteristics with reasonable accuracy for the preliminary design steps, which saves time and resources in the early design stages.

Peripheral nerve injuries significantly impact patients’ quality of life and poor functional recovery. Chitosan–ufasomes (CTS–UFAs) exhibit biomimetic features, making them a viable choice for developing novel transdermal delivery for neural repair. This study aimed to investigate the role of CTS–UFAs loaded with the propranolol HCl (PRO) as a model drug in enhancing sciatica in cisplatin-induced sciatic nerve damage in rats. Hence, PRO–UFAs were primed, embedding either span 20 or 60 together with oleic acid and cholesterol using a thin-film hydration process based on full factorial design (24). The influence of formulation factors on UFAs’ physicochemical characteristics and the optimum formulation selection were investigated using Design-Expert® software. Based on the optimal UFA formulation, PRO–CTS–UFAs were constructed and characterized using transmission electron microscopy, stability studies, and ex vivo permeation. In vivo trials on rats with a sciatic nerve injury tested the efficacy of PRO–CTS–UFA and PRO–UFA transdermal hydrogels, PRO solution, compared to normal rats. Additionally, oxidative stress and specific apoptotic biomarkers were assessed, supported by a sciatic nerve histopathological study. PRO–UFAs and PRO–CTS–UFAs disclosed entrapment efficiency of 82.72 ± 2.33% and 85.32 ± 2.65%, a particle size of 317.22 ± 6.43 and 336.12 ± 4.9 nm, ζ potential of −62.06 ± 0.07 and 65.24 ± 0.10 mV, and accumulatively released 70.95 ± 8.14% and 64.03 ± 1.9% PRO within 6 h, respectively. Moreover, PRO–CTS–UFAs significantly restored sciatic nerve structure, inhibited the cisplatin-dependent increase in peripheral myelin 22 gene expression and MDA levels, and further re-established sciatic nerve GSH and CAT content. Furthermore, they elicited MBP re-expression, BCL-2 mild expression, and inhibited TNF-α expression. Briefly, our findings proposed that CTS–UFAs are promising to enhance PRO transdermal delivery to manage sciatic nerve damage.

Background: Itraconazole (ITZ) is an antiangiogenic agent recognized as a potent suppressor of endothelial cell growth that suppresses angiogenesis. Nevertheless, its exploitation is significantly restricted by its low bioavailability and systematic side effects. The objective of this study was to utilize glycerosomes (GLY), glycerol-developed vesicles, as innovative nanovesicles for successful ITZ pulmonary drug delivery. Methods: The glycerosomes were functionalized with hyaluronic acid (HA-GLY) to potentiate the anticancer efficacy of ITZ and extend its local bio-fate. ITZ-HA-GLY were fabricated using soybean phosphatidylcholine, tween 80, HA, and sonication time via a thin-film hydration approach according to a 24 full factorial design. The impact of formulation parameters on ITZ-HA-GLY physicochemical properties, as well as the optimal formulation option, was evaluated using Design-Expert®. Sulphorhodamine-B (SRB) colorimetric cytotoxicity assay of the optimized ITZ-HA-GLY versus ITZ suspension was explored in the human A549 cell line. The in vivo pharmacokinetics and bio-distribution examined subsequent to intratracheal administrations of ITZ suspension, and ITZ-HA-GLY were scrutinized in rats. Results: The optimized ITZ-HA-GLY unveiled vesicles of size 210.23 ± 6.43 nm, zeta potential of 41.06 ± 2.62 mV, and entrapment efficiency of 73.65 ± 1.76%. Additionally, ITZ-HA-GLY manifested a far lower IC50 of 13.03 ± 0.2 µg/mL on the A549 cell line than that of ITZ suspension (28.14 ± 1.6 µg/mL). Additionally, the biodistribution analysis revealed a higher concentration of ITZ-HA-GLY within the lung tissues by 3.64-fold as compared to ITZ suspension. Furthermore, the mean resistance time of ITZ-HA-GLY declined more slowly with 14 h as compared to ITZ suspension, confirming the accumulation of ITZ inside the lungs and their promising usage as a target for the treatment of lung disease. Conclusions: These data indicate that the improved ITZ-HA-GLY demonstrates significant promise and represents an exciting prospect in intratracheal delivery systems for lung cancer treatment, meriting further investigation.

Background/Objectives: Raloxifene (RLF) is a therapeutic option for invasive breast cancer because it blocks estrogen receptors selectively. Low solubility, limited targeting, first-pass action, and poor absorption are some of the challenges that make RLF in oral form less effective. This study aimed to create an intra-tumoral in situ pH-responsive formulation of RLF–invasome (IPHRLI) for breast cancer treatment, with the goals of sustaining RLF release, minimizing adverse effects, and enhancing solubility, bioavailability, targeting, and effectiveness. Methods: Numerous RLF–invasome formulations were optimized using design expert software (version 12.0.6.0, StatEase Inc., Minneapolis, MN, USA). Integrating an optimal formulation with an amalgam of chitosan and glyceryl monooleate resulted in the IPHRLI formulation. In vivo testing of the IPHRLI formulation was conducted utilizing the Ehrlich cancer model. Results: Requirements for an optimum RLF–invasome formulation were met by a mixture of phospholipids (2.46%), ethanol (2.84%), and cineole (0.5%). The IPHRLI formulation substantially sustained its release by 75.41% after 8 h relative to free RLF. The bioavailability of intra-tumoral IPHRLI was substantially raised by 4.07-fold compared to oral free RLF. Histopathological and tumor volume analyses of intra-tumoral IPHRLI confirmed its efficacy and targeting effect. Conclusions: the intra-tumoral administration of the IPHRLI formulation may provide a potential strategy for breast cancer management.

A simple and efficient method for derivatization of the pyrimidine nucleus is developed. The readily available 6-amino-2-thioxo-2,3-dihydropyrimidin-4(1 H )-one has been used as a versatile building block for the synthesis of thioxopyrimidine derivatives. A variety of novel fused pyrimidines has been prepared via nucleophilic and/or electrophilic reactions of thioxopyrimidine derivatives. The structures of the newly synthesized products have been deduced on the basis of elemental analysis and spectral data.

Urinary bladder entrapment or incarceration within pelvic fracture have been described in many reports in the literature, most of which were reported in adult patients. We describe a case of a 14-year-old boy presented with isolated locked symphysis pubis disruption after falling from a height. His initial evaluation was negative for any other associated injuries. The decision was made to treat him surgically by open reduction and internal fixation using a symphyseal plate; however, upon completing the Pfannenstiel incision, the surgeon faced a soft tissue mass hindering bony fragment dissection; upon careful examination, the soft tissue mass turned out to be entrapped urinary bladder within the symphyseal disruption. After careful soft tissue dissection, and with the help of Jungbluth distractor, the disruption was over-distracted, the bladder was freed entirely (which was intact) and reduced to its position, followed by the application of a symphyseal plate in a reduced symphysis pubis position. The patient did well postoperatively, and at three months follow up, the disruption and fracture united, and there were no urinary-related symptoms. Although rare, urinary bladder entrapment within an element of anterior pelvic fracture could be a reason for the difficult reduction; careful evaluation and steady soft tissue dissection are paramount for avoiding undue iatrogenic urinary bladder injury.