Enhancement of magnetization and optical properties of CuFe2O4/ZnFe2O4 core/shell nanostructure.

In this work, core/shell of CuFe2O4/ZnFe2O4 nanostructure composite was prepared by hydrothermal method. X-ray diffraction (XRD) analysis, transmission electron microscope imaging, energy dispersive X-ray (EDX), and Fourier transform infrared techniques were used to prove the phase formation, morphology, elemental analysis, and cation distribution of core/shell structure, respectively. Furthermore, measurement of the optical properties proved the decrease of photoluminescence (PL) efficiency. The magnetic measurements showed an enhancement of the magnetization by about 63% relative to pure Cu ferrite, and the magnetization curve exhibited superparamagnetic behavior. These results were explained in terms of the depression of the magnetic dead layer thickness in the core/shell structure. The results unleash the promising applications of the prepared samples as transformer cores in the high frequency range and as a photocatalytic agent for water purification and hydrogen production.

Myocardial Strain for the Differentiation of Myocardial Involvement in the Post-Acute Sequelae of COVID-19-A Multiparametric Cardiac MRI Study.

Myocardial involvement was shown to be associated with an unfavorable prognosis in patients with COVID-19, which could lead to fatal outcomes as in myocardial injury-induced arrhythmias and sudden cardiac death. We hypothesized that magnetic resonance imaging (MRI) myocardial strain parameters are sensitive markers for identifying subclinical cardiac dysfunction associated with myocardial involvement in the post-acute sequelae of COVID-19 (PASC). This study evaluated 115 subjects, including 65 consecutive COVID-19 patients, using MRI for the assessment of either post-COVID-19 myocarditis or other cardiomyopathies. Subjects were categorized, based on the results of the MRI exams, as having either 'suspected' or 'excluded' myocarditis. A control group of 50 matched individuals was studied. Along with parameters of global cardiac function, the MRI images were analyzed for measurements of the myocardial T1, T2, extracellular volume (ECV), strain, and strain rate. Based on the MRI late gadolinium enhancement and T1/T2/ECV mappings, myocarditis was suspected in 7 out of 22 patients referred due to concern of myocarditis and in 9 out of 43 patients referred due to concern of cardiomyopathies. The myocardial global longitudinal, circumferential, and radial strains and strain rates in the suspected myocarditis group were significantly smaller than those in the excluded myocarditis group, which in turn were significantly smaller than those in the control group. The results showed significant correlations between the strain, strain rate, and global cardiac function parameters. In conclusion, this study emphasizes the value of multiparametric MRI for differentiating patients with myocardial involvement in the PASC based on changes in the myocardial contractility pattern and tissue structure.

2nd Window NIR Imaging of Radiation Injury Mitigation Provided by Reduced Notch-Dll4 Expression on Vasculature.

PURPOSE: Vascular endothelium plays a central role in the pathogenesis of acute and chronic radiation injuries, yet the mechanisms which promote sustained endothelial dysfunction and contribute to late responding organ failure are unclear. We employed 2nd window (> 1100 nm emission) Near-Infrared (NIR) imaging using indocyanine green (ICG) to track and define the role of the notch ligand Delta-like ligand 4 (Dll4) in mediating vascular injury in two late-responding radiosensitive organs: the lung and kidney. PROCEDURES: Consomic strains of female Salt Sensitive or SS (Dll4-high) and SS with 3rd chromosome inherited from Brown Norway, SS.BN3 (Dll4-low) rats at ages 11-12 weeks were used to demonstrate the impact of reduced Dll4 expression on long-term vascular integrity, renal function, and survival following high-dose 13 Gy partial body irradiation at 42- and 90 days post-radiation. 2nd window dynamic NIR fluorescence imaging with ICG was analyzed with physiology-based pharmacokinetic modeling and confirmed with assays of endothelial Dll4 expression to assess the role of endogenous Dll4 expression on radiation injury protection. RESULTS: We show that SS.BN3 (Dll4-low) rats are relatively protected from vascular permeability disruption compared to the SS (Dll4-high) strain. We further demonstrated that SS.BN3 (Dll4-low) rats have reduced radiation induced loss of CD31+ vascular endothelial cells, and increased Dll4 vascular expression is correlated with vascular dysfunction. CONCLUSIONS: Together, these data suggest Dll4 plays a key role in pathogenesis of radiation-induced vascular injury to the lung and kidney.

Vitamin B12 status among asymptomatic young adult females and its association with some anthropometric and biochemical parameters: A cross-sectional study from Makkah (cobalamin deficiency in young adult females).

This study was designed to measure the prevalence of vitamin B12 deficiency among young adult females in Makkah City and study its correlation with some anthropometric and biochemical indicators. A cross-sectional study and a detailed questionnaire were used to collect information from 402 young women aged 19 to 22 years, who were university students. Moreover, dietary assessments using a validated food frequency questionnaire and anthropometric measurements were performed. The mean values of serum vitamin B12, serum folate, hemoglobin, and body mass index (BMI) were 343.29 ±â€…148.16 pg/mL, 12.72 ±â€…2.62 ng/mL, 12.69 ±â€…1.41 g/dL, and 22.64 ±â€…4.24 kg/m2, respectively. About three-quarters of the study sample had normal vitamin B12 levels, while the rest had vitamin B12 deficiency. Meanwhile, a significant negative association (r = -0.201, P = .048) was found between abdominal fat and serum vitamin B12 levels. This study concluded that the young adult females' population from Makkah City is among the risk groups for vitamin B12 deficiency, which is highly correlated with inappropriate values of weight, body fat, and some blood indices. Appropriate dietary interventions and awareness are needed for this population.

Profibrotic COVID-19 subphenotype exhibits enhanced localized ER-dependent HSP47+ expression in cardiac myofibroblasts in situ.

We recently described a subgroup of autopsied COVID-19 subjects (∼40%), termed 'profibrotic phenotype,' who exhibited clusters of myofibroblasts (Mfbs), which were positive for the collagen-specific chaperone heat shock protein 47 (HSP47+) in situ. This report identifies increased, localized (hot spot restricted) expression of αSMA, COLα1, POSTN and FAP supporting the identity of HSP47+ cells as myofibroblasts and characterizing a profibrotic extracellular matrix (ECM) phenotype. Coupled with increased GRP78 in COVID-19 subjects, these data could reflect induction of the unfolded protein response for mitigation of proteostasis (i.e., protein homeostasis) dysfunction in discrete clusters of cells. ECM shifts in selected COVID-19 subjects occur without significant increases in either global trichrome positive staining or myocardial injury based quantitively on standard H&E scoring. Our findings also suggest distinct mechanism(s) for ECM remodeling in the setting of SARS-CoV-2 infection. The ratio of CD163+/CD68+ cells is increased in hot spots of profibrotic hearts compared with either controls or outside of hot spots in COVID-19 subjects. In sum, matrix remodeling of human COVID-19 hearts in situ is characterized by site-restricted profibrotic mediated (e.g., HSP47+ Mfbs, CD163+ Mφs) modifications in ECM (i.e., COLα1, POSTN, FAP), with a strong correlation between COLα1 and HSP47+cells within hot spots. Given the established associations of viral infection (e.g., human immunodeficiency virus; HIV), myocardial fibrosis and sudden cardiac death, early screening tools (e.g., plasma biomarkers, noninvasive cardiac magnetic resonance imaging) for diagnosis, monitoring and treatment of fibrotic ECM remodeling are warranted for COVID-19 high-risk populations.

Real-Time Strain-Encoding Cardiovascular MRI for Assessment of Regional Heart Function in Tetralogy of Fallot Patients.

BACKGROUND: Tetralogy of Fallot (ToF) is the most common form of cyanotic congenital heart disease, where right ventricular (RV) function is an important determinant of subsequent intervention. OBJECTIVE: In this study, we evaluate the feasibility of fast strain-encoding (fastSENC; a one-heartbeat sequence) magnetic resonance imaging (MRI) for assessing regional cardiac function in ToF. METHOD: FastSENC was implemented to characterize regional circumferential (Ecc) and longitudinal (Ell) strains in the left ventricle (LV) and RV in post-repair ToF. Data analysis was conducted to compare strain measurements in the RV to those in the LV, as well as to those generated by the MRI Tissue-Tracking (MRI-TT) technique, and to assess the relationship between strain and ejection fraction (EF). RESULTS: Despite normal LVEF (55±8.5%), RVEF was borderline (46±6.4%), but significantly lower than LVEF. RV strains (RV-Ell=-20.2±2.9%, RV-Ecc=-15.7±6.4%) were less than LV strains (LV-Ell=-21.7±3.7%, LV-Ecc=-18.3±4.7%), and Ell was the dominant strain component. Strain differences between fastSENC and MRI-TT were less significant in RV than in LV. There existed moderate and weak correlations for RV-Ecc and RV-Ell, respectively, against RVEF. Compared to LV strain, RV strain showed regional heterogeneity with a trend for reduced strain from the inferior to anterior regions. Inter-ventricular strain delay was larger for Ell (64±47ms) compared to Ecc (36±40ms), reflecting a trend for contraction dyssynchrony. CONCLUSION: FastSENC allows for characterizing subclinical regional RV dysfunction in ToF. Due to its sensitivity for evaluating regional myocardial contractility patterns and real-time imaging capability without the need for breath-holding, fastSENC makes it more suitable for evaluating RV function in ToF.

Aortic Remodeling Kinetics in Response to Coarctation-Induced Mechanical Perturbations.

Background: Coarctation of the aorta (CoA; constriction of the proximal descending thoracic aorta) is among the most common congenital cardiovascular defects. Coarctation-induced mechanical perturbations trigger a cycle of mechano-transduction events leading to irreversible precursors of hypertension including arterial thickening, stiffening, and vasoactive dysfunction in proximal conduit arteries. This study sought to identify kinetics of the stress-mediated compensatory response leading to these alterations using a preclinical rabbit model of CoA. Methods: A prior growth and remodeling (G&R) framework was reformulated and fit to empirical measurements from CoA rabbits classified into one control and nine CoA groups of various severities and durations (n = 63, 5-11/group). Empirical measurements included Doppler ultrasound imaging, uniaxial extension testing, catheter-based blood pressure, and wire myography, yielding the time evolution of arterial thickening, stiffening, and vasoactive dysfunction required to fit G&R constitutive parameters. Results: Excellent agreement was observed between model predictions and observed patterns of arterial thickening, stiffening, and dysfunction among all CoA groups. For example, predicted vascular impairment was not significantly different from empirical observations via wire myography (p-value > 0.13). Specifically, 48% and 45% impairment was observed in smooth muscle contraction and endothelial-dependent relaxation, respectively, which were accurately predicted using the G&R model. Conclusions: The resulting G&R model, for the first time, allows for prediction of hypertension precursors at neonatal ages that is currently challenging to examine in preclinical models. These findings provide a validated computational tool for prediction of persistent arterial dysfunction and identification of revised severity-duration thresholds that may ultimately avoid hypertension from CoA.

Temporal evolution of mechanical stimuli from vascular remodeling in response to the severity and duration of aortic coarctation in a preclinical model.

Coarctation of the aorta (CoA) is one of the most common congenital cardiovascular diseases. CoA patients frequently undergo surgical repair, but hypertension (HTN) is still common. The current treatment guideline has revealed irreversible changes in structure and function, yet revised severity guidelines have not been proposed. Our objective was to quantify temporal alterations in mechanical stimuli and changes in arterial geometry in response to the range of CoA severities and durations (i.e. age of treatment) seen clinically. Rabbits were exposed to CoA resulting in peak-to-peak blood pressure gradient (BPGpp) severities of ≤ 10, 10-20, and ≥ 20 mmHg for a duration of ~ 1, 3, or 20 weeks using permanent, dissolvable, and rapidly dissolvable sutures. Elastic moduli and thickness were estimated from imaging and longitudinal fluid-structure interaction (FSI) simulations were conducted at different ages using geometries and boundary conditions from experimentally measured data. Mechanical stimuli were characterized including blood flow velocity patterns, wall tension, and radial strain. Experimental results show vascular alternations including thickening and stiffening proximal to the coarctation with increasing severity and/or duration of CoA. FSI simulations indicate wall tension in the proximal region increases markedly with coarctation severity. Importantly, even mild CoA induced stimuli for remodeling that exceeds values seen in adulthood if not treated early and using a BPGpp lower than the current clinical threshold. The findings are aligned with observations from other species and provide some guidance for the values of mechanical stimuli that could be used to predict the likelihood of HTN in human patients with CoA.

Collagen-Specific HSP47+ Myofibroblasts and CD163+ Macrophages Identify Profibrotic Phenotypes in Deceased Hearts With SARS-CoV-2 Infections.

Background Cardiac fibrosis complicates SARS-CoV-2 infections and has been linked to arrhythmic complications in survivors. Accordingly, we sought evidence of increased HSP47 (heat shock protein 47), a stress-inducible chaperone protein that regulates biosynthesis and secretion of procollagen in heart tissue, with the goal of elucidating molecular mechanisms underlying cardiac fibrosis in subjects with this viral infection. Methods and Results Using human autopsy tissue, immunofluorescence, and immunohistochemistry, we quantified Hsp47+ cells and collagen α 1(l) in hearts from people with SARS-CoV-2 infections. Because macrophages are also linked to inflammation, we measured CD163+ cells in the same tissues. We observed irregular groups of spindle-shaped HSP47+ and CD163+ cells as well as increased collagen α 1(I) deposition, each proximate to one another in "hot spots" of ≈40% of hearts after SARS-CoV-2 infection (HSP47+ P<0.05 versus nonfibrotics and P<0.001 versus controls). Because HSP47+ cells are consistent with myofibroblasts, subjects with hot spots are termed "profibrotic." The remaining 60% of subjects dying with COVID-19 without hot spots are referred to as "nonfibrotic." No control subject exhibited hot spots. Conclusions Colocalization of myofibroblasts, M2(CD163+) macrophages, and collagen α 1(l) may be the first evidence of a COVID-19-related "profibrotic phenotype" in human hearts in situ. The potential public health and diagnostic implications of these observations require follow-up to further define mechanisms of viral-mediated cardiac fibrosis.

Rapid and Simple Method for Measuring Petroleum Asphaltenes by the Centrifugation Technique.

Asphaltenes are heavy constituents of crude oil which affect the flow and viscosity of crude oil. They also stabilize water-in-oil emulsions which makes the separation process of water from oil during the primary treatment processes for crude oils more difficult and costly. Measuring asphaltenes has great importance, especially for crude oil production companies. Gravimetric and spectroscopic measurement methods are the basic techniques used by international references such as ASTM and IP. A new methodology has been introduced as a modification of ASTM D6560 gravimetric methodology by using the centrifugation technique in the separation of asphaltenes for different oil samples with the API gravity change from 17.4 (oil S1) to 39.8 (oil S5). The new methodology has the advantages of consuming little time, and multiple sample processing and can be done in the field and also in the lab. Moreover, it has good repeatability, reproducibility, and working range values compared to the reference gravimetric ASTM and IP methods. The repeatability of the new method was found to be 8.0% at its maximum value (S1, has a low asphaltene content), while the minimum value was found to be 3.75% (S10, has the highest asphaltene content). It was found that the maximum reproducibility value was 17.0% for the S1 sample and the minimum was 0.0% for S9 and S10 samples.

Facile Synthesis of Some Coumarin Derivatives and Their Cytotoxicity through VEGFR2 and Topoisomerase II Inhibition.

Novel semisynthetic coumarin derivatives were synthesized to be developed as chemotherapeutic anticancer agents through topoisomerase II, VEGFR2 inhibition that leads to apoptotic cancer cell death. The coumarin amino acids and dipeptides derivatives were prepared by the reaction of coumarin-3-carboxylic acid with amino acid methyl esters following the N,N-dicyclohexylcarbodiimide (DCC) method and 1-hydroxy-benzotriazole (HOBt), as coupling reagents. The synthesized compounds were screened towards VEGFR2, and topoisomerase IIα proteins to highlight their binding affinities and virtual mechanism of binding. Interestingly, compounds 4k (Tyr) and 6c (ß-Ala-L-Met) shared the activity towards the three proteins by forming the same interactions with the key amino acids, such as the co-crystallized ligands. Both compounds 4k and 6c exhibited potent cytotoxic activities against MCF-7 cells with IC50 values of 4.98 and 5.85 µM, respectively causing cell death by 97.82 and 97.35%, respectively. Validating the molecular docking studies, both compounds demonstrated promising VEGFR-2 inhibition with IC50 values of 23.6 and 34.2 µM, compared to Sorafenib (30 µM) and topoisomerase-II inhibition with IC50 values of 4.1 and 8.6 µM compared to Doxorubicin (9.65 µM). Hence, these two promising compounds could be further tested as effective and selective target-oriented active agents against cancer.

One-pot multi-functional finishing of wool fabric using reactive nonionic softener.

Crossbred wool is widely used in the textile and clothing fields. Nevertheless, the surface roughness of crossbred wool fabric is higher than that of Merino wool. Herein we propose a reactive nonionic softener (RNS) based on fatty acid (FA) and 2-amino-2-methyl propane diol (AMPD) to impart desirable multi-functions for crossbred wool fabric, such as improved smoothness, enhanced wettability, and induced resistance to felting shrinkage. Adopting the pad-dry-cure method, treatment of wool with the said softener was carried out using different concentrations of FA/AMPD condensate at different curing temperatures and durations. The results showed that the highest fabric surface smoothness was attained when wool fabric was treated with 3.5% (o.w.f.) RNS, and the curing temperature and time were 130 °C and 5 min, respectively. The surface smoothness of the treated fabric and its resistance to felting shrinkage were increased by 21.7% and 90% respectively. The effects of treatment of wool with the RNS on its bending stiffness, air and water permeability, yellowness, electrostatic charge, and ultraviolet protection factor (UPF) were monitored. The reaction mechanism between the used RNS and wool was studied using FTIR spectroscopy. Scanning electron microscopic investigation showed a layer of the used RNS on the surface of the treated fabric. The finished fabric retained its air permeability and dyeability with anionic dye. The imparted fabric smoothness was find to be durable against washing until 5 washing cycles, and decreased by 5.5% of after 10 washing cycles respectively.

Clinical, Experimental, and Computational Validation of a New Doppler-Based Index for Coarctation Severity Assessment.

BACKGROUND: Long-term morbidity including hypertension often persists in coarctation patients despite current guidelines. Coarctation severity can be invasively assessed via peak-to-peak catheter pressure gradient (PPCG), which is estimated noninvasively via simplified Bernoulli equation and conventionally reported as peak instantaneous Doppler gradient (PIDG). However, underlying simplifications of the equation limit diagnostic accuracy. We studied the diagnostic performance of a new Doppler-based diastolic index called the continuous flow pressure gradient (CFPG) versus conventional indices in assessing coarctation severity. METHODS: In a rabbit model mimicking human aortic coarctation, temporal blood pressure waveforms revealed the diastolic instantaneous pressure gradients and spectral Doppler features impacted by coarctation severity. We therefore hypothesized that CFPG provides superior correlation with coarctation gradients measured invasively. PIDG and CFPG were quantified using color flow echocardiography in humans and rabbits with discrete coarctations. Results were compared with PPCG in rabbits (n = 34) and arm-leg systolic gradients (n = 25) in humans via 1-way analysis of variance, Pearson's correlation, linear regression, and Bland-Altman analysis. RESULTS: A threshold of CFPG ≥ 4.6 mm Hg was identified via the Youden index as representative of PPCG ≥ 20 mm Hg (the current guideline value for coarctation intervention) in rabbits, while a CFPG ≥1.0 mm Hg represented an arm-leg systolic gradient ≥20 mm Hg in humans. Accuracy measures revealed superior correlation of CFPG (R2 > 0.80) and mild receiver operating characteristic improvement (area under the receiver operating characteristic curve, 0.94-0.95) compared with PIDG (R2 < 0.63; area under the receiver operating characteristic curve, 0.89-0.95). Inter-/intraobserver variability tested by intraclass correlation coefficient revealed measurement reliability with differences ≤8.2% and 10.7%, respectively. Computational simulations of anesthetized versus conscious hemodynamics showed parameters were minimally impacted by isoflurane inherent in the data used to derive CFPG. These results confirm the potential diagnostic accuracy of CFPG in echocardiography-based coarctation severity assessment. We are optimistic that CFPG will be useful for translation of results from preclinical studies that revisit current guidelines to limit morbidity in humans with aortic coarctation.

Design, Synthesis and Molecular Docking of Novel Acetophenone-1,2,3-Triazoles Containing Compounds as Potent Enoyl-Acyl Carrier Protein Reductase (InhA) Inhibitors.

New medications are desperately needed to combat rising drug resistance among tuberculosis (TB) patients. New agents should ideally work through unique targets to avoid being hampered by preexisting clinical resistance to existing treatments. The enoyl-acyl carrier protein reductase InhA of M. tuberculosis is one of the most crucial targets since it is a promising target that has undergone extensive research for anti-tuberculosis drug development. A well-known scaffold for a variety of biological activities, including antitubercular activity, is the molecular linkage of a1,2,3-triazole with an acetamide group. As a result, in the current study, which was aided by ligand-based molecular modeling investigations, 1,2,3-triazolesweredesigned and synthesized adopting the CuAAC aided cycloaddition of 1-(4-(prop-2-yn-1-yloxy)phenyl)ethanone with appropriate acetamide azides. Standard spectroscopic methods were used to characterize the newly synthesized compounds. In vitro testing of the proposed compounds against the InhA enzyme was performed. All the synthesized inhibitors completely inhibited the InhA enzyme at a concentration of 10 µM that exceeded Rifampicin in terms of activity. Compounds 9, 10, and 14 were the most promising InhA inhibitors, with IC50 values of 0.005, 0.008, and 0.002 µM, respectively. To promote antitubercular action and investigate the binding manner of the screened compounds with the target InhA enzyme's binding site, a molecular docking study was conducted.

Preparation of fatty acid-amino diol condensate and its utilization as a durable nonionic softener for PAN fabrics.

Polyacrylonitrile (PAN) fabrics meet the customers' requirements in many aspects. Nevertheless, PAN fabrics suffer from low moisture regain and the accumulation of electrostatic charges on the fabric surface. Some PAN products exhibit rough a surface which is uncomfortable for human skin. Herein, we synthesized a new hydrophilic nonionic softener by reacting a fatty acid (FA), extracted from wool wax, with 2-amino-2-methyl-1,3-propanediol (AMPD). Adopting the pad-dry-cure technique, the synthesized softener was chemically bound to pretreated PAN fabrics. Without deterioration of the fabrics' mechanical properties, new functions have been imparted to the treated PAN fabrics, viz., silk-like hand, induced resistance to the accumulation of electrostatic charges, and improved wettability. Fourier-transform infrared (FTIR) spectroscopy and carbon-13 nuclear magnetic resonance (13C-NMR) were utilized for the structure elucidation of the prepared softener as well as to determine whether AMPD reacts with the fatty acid through its amino or hydroxyl group. The mechanism of the preparation of the softener as well as its mode of action on PAN fabrics were proposed. The effects of the applied softener on air and water permeability, ultraviolet protection factor (UPF), stiffness, tensile properties, and yellowness of the treated fabric were studied. The scanning electron micrographs of the treated fabric revealed the existence of a layer of the applied softener on the fabric surface. The finished fabric was found to be durable against washing for up to 20 cycles in terms of the fabric smoothness and durability.

Harnessing ROS-Induced Oxidative Stress for Halting Colorectal Cancer via Thiazolidinedione-Based SOD Inhibitors.

Based on the "canonical" view of reactive oxygen species' (ROS) contribution to carcinogenesis, ROS induce oxidative stress and promote various tumor progression events. However, tumor cells also need to defend themselves against oxidative damage. This "heresy" was supported by several recent studies underlining the role of cellular antioxidant capacity in promoting metastasis and resistance to chemotherapy. Accordingly, harnessing the ROS-induced oxidative stress via selective suppression of the cancer antioxidant defense machinery has been launched as an innovative anticancer strategy. Within this approach, pharmacological inhibition of superoxide dismutases (SODs), the first-line defense antioxidant enzymes for cancer cells, selectively kills tumor cells and circumvents their acquired resistance. Various SOD inhibitors have been introduced, of which some were tolerated in clinical trials. However, the hit SOD inhibitors belong to diverse chemical classes and lack comprehensive structure-activity relationships (SAR). Herein, we probe the potential of newly synthesized benzylidene thiazolidinedione derivatives to inhibit SOD in colorectal cancer with special emphasis on their effects on correlated antioxidant enzymes aldehyde dehydrogenase 1 (ALDH1) and glutathione peroxidase (GPx). This may possibly bring a new dawn for utilizing thiazolidinediones (TZDs) in cancer therapy through SOD inhibition mechanisms. The preliminary 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that all of the evaluated TZDs exhibited excellent safety profiles on normal human cells, recording an EC100 of up to 47.5-folds higher than that of doxorubicin. Compounds 3c, 6a, and 6e (IC50 = 4.4-4.7 µM) were superior to doxorubicin and other derivatives against Caco-2 colorectal cancer cells within their safe doses. The hit anticancer agents inhibited SOD (IC50 = 97.2-228.8 µM). Then, they were selected for further in-depth evaluation on the cellular level. The anticancer IC50 doses of 3c, 6a, and 6e diminished the antioxidant activities of SOD (by 29.7, 70.1, and 33.3%, respectively), ALDH1A (by 85.92, 95.84, and 86.48%, respectively), and GPX (by 50.17, 87.03, and 53.28%, respectively) in the treated Caco-2 cells, elevating the Caco-2 cellular content of ROS by 21.42, 7.863, and 8.986-folds, respectively. Docking simulations were conducted to display their possible binding modes and essential structural features. Also, their physicochemical parameters and pharmacokinetic profiles formulating drug-likeness were computed.

Novel Hybrid 1,2,4- and 1,2,3-Triazoles Targeting Mycobacterium Tuberculosis Enoyl Acyl Carrier Protein Reductase (InhA): Design, Synthesis, and Molecular Docking.

Tuberculosis (TB) caused by Mycobacterium tuberculosis is still a serious public health concern around the world. More treatment strategies or more specific molecular targets have been sought by researchers. One of the most important targets is M. tuberculosis' enoyl-acyl carrier protein reductase InhA which is considered a promising, well-studied target for anti-tuberculosis medication development. Our team has made it a goal to find new lead structures that could be useful in the creation of new antitubercular drugs. In this study, a new class of 1,2,3- and 1,2,4-triazole hybrid compounds was prepared. Click synthesis was used to afford 1,2,3-triazoles scaffold linked to 1,2,4-triazole by fixable mercaptomethylene linker. The new prepared compounds have been characterized by different spectroscopic tools. The designed compounds were tested in vitro against the InhA enzyme. At 10 nM, the inhibitors 5b, 5c, 7c, 7d, 7e, and 7f successfully and totally (100%) inhibited the InhA enzyme. The IC50 values were calculated using different concentrations. With IC50 values of 0.074 and 0.13 nM, 7c and 7e were the most promising InhA inhibitors. Furthermore, a molecular docking investigation was carried out to support antitubercular activity as well as to analyze the binding manner of the screened compounds with the target InhA enzyme's binding site.

Effect of Two Different Rehabilitation Approaches on Pulmonary Functional Tests, Neuromuscular Functions and Quality of Life in Juvenile Myasthenia Gravis: A Randomized Controlled Trial Study.

Background and Objectives: Children with juvenile myasthenia gravis have a variety of symptoms, ranging from isolated intermittent ocular complaints to overall muscle weakness with or without respiratory insufficiency. This study aimed to investigate the efficacy of a specialized physical therapy with or without partial body weight supported treadmill training on pulmonary functional tests, neuromuscular functions, and quality of life. Materials and Methods: Thirty children, ranging in age from 13 to 16 years, were distributed randomly into two study groups (A or B). Both groups underwent a designed physical therapy program. In addition, group A underwent the partial body weight supported treadmill training. The treatment was conducted three times a week for 12 weeks successively. Pulmonary functional tests (FVC, FEV1, PEFR, and MVV), neuromuscular function tests (compound motor action potential, isometric muscle force of biceps brachii and rectus femoris, balance, walking endurance, and fatigue), and quality of life were measured before and after 12 successive weeks. Results: A significant improvement in all investigated variables were recorded in both groups in favor of group A. Conclusions: Both a specialized physical therapy and partial body weight supported treadmill training are effective in terms of enhancing pulmonary functional tests, neuromuscular functions, and quality of life. Partial body weight supported treadmill training is an excellent adjunctive to the physical therapy program.

Myocardial Contractility Pattern Characterization in Radiation-Induced Cardiotoxicity Using Magnetic Resonance Imaging: A Pilot Study with ContractiX.

Radiation therapy (RT) plays an integral role in treating thoracic cancers, despite the risk of radiation-induced cardiotoxicity. We hypothesize that our newly developed magnetic resonance imaging (MRI)-based contractility index (ContractiX) is a sensitive marker for early detection of RT-induced cardiotoxicity in a preclinical rat model of thoracic cancer RT. Adult salt-sensitive rats received image-guided heart RT and were imaged with MRI at 8 weeks and 10 weeks post-RT or sham. The MRI exam included cine and tagging sequences to measure left-ventricular ejection fraction (LVEF), mass, myocardial strain, and ContractiX. Furthermore, ventricular torsion, diastolic strain rate, and mechanical dyssynchrony were measured. Statistical analyses were performed between the sham, 8 weeks post-RT, and 10 weeks post-RT MRI parameters. The results showed that both LVEF and myocardial mass increased post-RT. Peak systolic strain and ContractiX significantly decreased post-RT, with a more relative reduction in ContractiX compared to strain. ContractiX showed an inverse nonlinear relationship with LVEF and continuously decreased with time post-RT. While early diastolic strain rate and mechanical dyssynchrony significantly changed post-RT, ventricular torsion changes were not significant post-RT. In conclusion, ContractiX measured via non-contrast MRI is a sensitive early marker for the detection of subclinical cardiac dysfunction post-RT, and it is superior to other MRI cardiac measures.