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Abstract The anticancer, antimicrobial, and insecticidal activities of sarcotrocheliol (1) and cholesterol (2) obtained from the soft coral Sarcophyton trocheliophorum (S. trocheliophorum) were intensively studied. According to this study, both compounds 1 and 2 showed potential cytotoxicity towards the human colorectal carcinomaHCT-116 (IC50 10.4, 11.8 µg/mL) and human liver carcinoma HepG2 cell lines (IC50 8.8, 12.0 µg/mL), respectively. Compounds 1 and 2 were evaluated as potential inhibitors of caspase-3, a member of the cysteine protease family, which is considered a key enzyme in inducing cell apoptosis. Results showed that compounds 1 and 2 have induced apoptosis via up-regulation of caspase-3. Sarcotrocheliol (1) displayed antimicrobial activity against P. aeruginosa (15 mm), B. subtilis (15 mm), M. luteus (14 mm) and C. albicans (15 mm), with a MIC of 1.5 µg/mL against the reported test microorganisms. On the other hand, cholesterol (2) showed less activity towards P. aeruginosa (10 mm), B. subtilis (14 mm), S. aureus (12 mm) and C. albicans (10 mm) with MICs of 3.0, 1.5, 1.5 and 3.0 µg/mL against the tested microorganisms, respectively. Larvicidal activity revealed that compounds 1 and 2 induced remarkable toxicity against the third instar larvae of the mosquito, Culex pipiens even at concentration of 2 ppm. Adulticidal activity data showed that tested compounds are distinctly potent toxicants against the housefly, Musca domestica adult females. Overall, compound 2induced much more insecticidal activity than 1, and M. domestica adult females were more sensitive to tested compounds than C. pipiens larvae. Computationally, Density Functional Theory (DFT) analyses revealed that compound 2 had a higher dipole moment and lower band gap energy when compared to compound 1. So, compounds 2 is chemically more reactive and less stable than compound 1. According to the molecular docking study against PDB IDs: 3KJF, 5UHF and 1ACJ, compounds 1 and 2 demonstrated their activity mode as anticancer, antimicrobial, and insecticidal agents. The compounds exerted many interactions and showed high binding to the proteins, recognizing their potential as drug candidates with broad bioactivities.

Abstract A wind turbine system (WTS) is a highly coupled and nonlinear system where the output power depends upon highly uncertain wind speed. Therefore, the quality of produced power becomes a challenging problem for researchers. Direct Vector Control (DVC) is a powerful and widely utilized power control strategy to deal with winds that vary rapidly and randomly. As a result, this article employed the newly developed Social Spider Optimization (SSO) technique to optimize the design parameters of Fractional-Order Fuzzy Proportional-Integral with Derivative (FOFPID) regulator to maintain the output power of the studied DFIG-based WTS at the rated value under dynamic wind conditions. The suggested FOFPID controller integrates the capabilities of the Fuzzy intelligent regulator and the Fractional-Order controller, enhancing DFIG current control while allowing independent control of active and reactive power. The approach is incorporated within the DVC strategy of the DFIG’s rotor-side converter (RSC), replacing the conventional Proportional-Integral (PI) regulator in the internal current loops. Extensive performance evaluations are conducted under various operating conditions, including active power reference changes, parameter uncertainties, and rapid wind speed variations. Comparative analyses with SSO-optimized PID and Fuzzy regulators show that the FOFPID regulator performs better in terms of maximum overshoot, extreme undershoot, settling time, Total Harmonic Distortion (THD), and Weighted Total Harmonic Distortion (WTHD). The suggested FOFPID regulator also displays stronger robustness against parameters mismatch and weather change than other regulator architectures.

Testicular seminomas are the most common type of testicular tumor; atypical presentations can make diagnosis more challenging, leading to delayed treatment. Here, we present a 40-year-old previously healthy male who presented to the emergency department with severe right-sided scrotal swelling and pain. He had a diagnosed but untreated inguinal hernia. Physical examination revealed a large irreducible right inguinoscrotal swelling and tenderness. Doppler ultrasound reported herniated content in the right inguinal area, extending to the scrotum. Upon surgical exploration, a large right testicular tumor was discovered, surrounded by hematoma. A radical orchiectomy was performed, and the tumor was identified as a stage pT2 testicular seminoma. This case illustrates the diagnostic challenges posed by atypical presentations of testicular seminomas. A high index of suspicion and thorough clinical and radiological assessments are crucial for accurate diagnosis and management. In conclusion, large testicular seminomas presenting with acute pain mimicking strangulated hernias are rare. Comprehensive clinical and radiological evaluations are essential to avoid misdiagnosis and ensure appropriate surgical planning and patient management.

Abstract The aim of this study is to evaluate the role of serum level of Interleukin 6(IL-6) and Interleukin 17 (IL-17) in liver transplantation outcome for living recipients, Analyze the relation between the gene polymorphism and the occurrence of rejection after liver transplantation and Study the relation between the gene polymorphism and the occurrence of different infectious complications. The study was conducted in March 2023 and included 60 healthy volunteers from the National Liver Institute (NLI) blood bank at Menoufia University and 120 live donation liver recipient patients at NLI. During one month of liver transplantation, the cytokine levels (IL-17, IL-6 proteins, IL-6 G-174C, and IL-17 A rs2275913 gene polymorphism) and CD4 levels for 60 patients of 120 live donation liver recipient patients whom early reject transplanted tissue and the same parameters were measured after 6 months follow up for non-reject group. The main finding of this study was that the post-transplant rejection group and the post-transplant non-rejection and control groups differed significantly in the genotype frequency (CC, CG, and GG) or alleles of IL-6 G-174C (p = 0.011). On the other hand IL-17A rs2275913 gene polymorphism and its alleles (p = 0.71) showed no statistically significant difference. We also observed that serum IL-17 levels, with 100% specificity and 100% sensitivity threshold, will be more sensitive and specific than serum IL-6 and CD4 count in differentiating post-transplant rejection from non-rejection patients. The results showed that there was no significant relationship between the genotypes and serum levels of interleukins and the type and degree of rejection. Proinflammatory cytokines might be useful indicators for distinguishing and early identifying unfavorable outcomes after transplantation, allowing for prompt and effective treatment intervention. To evaluate these findings, prospective clinical trials are required.

Computed tomography (CT) multi-detector array has been heavily utilized over the past decade. While transforming an individual’s diagnosis, the risk of developing pathogenesis as a result remains a concern. The main aim of this institutional cumulative effective dose (CED) review is to highlight the number of adult individuals with a record of CED ≥ 100 mSv over a time span of 5 years. Further, we aim to roughly estimate both incidence and mortality life-attributable risks (LARs) for the shortlisted individuals. CT studies performed over one year, in one dedicated trauma and emergency facility, were retrospectively retrieved and analyzed. Individuals with historical radiological CED ≥ 100 mSv were short-listed. LARs were defined and established based on organ, age and gender. Out of the 4406 CT studies reviewed, 22 individuals were found with CED ≥ 100 mSv. CED varied amongst the short-listed individuals, with the highest CED registered being 223.0 mSv, for a 57-year-old male, cumulated over an average study interval of 46.3 days. The highest median mortality risk was for females, 214 per 100,000 registered for the age group 51–60 years. While certain clinical indications and diseases require close follow-up using radiological examinations, the benefit-to-risk ratio should be carefully considered, particularly when CT is requested.

Abstract Background The final decision to fast or not fast for routine lipid profile examination in a standard, healthy population is unclear. Whereas the United States and European protocols state that fasting for regular lipid analysis is unnecessary, the North American and Chinese guidelines still recommend fasting before routine lipid testing. Aim This study aimed to unravel the contradiction between the different protocols of lipid profile testing worldwide and clarify the effect of diet on lipid profile testing only in a regular, healthy population. Methods A literature search was conducted through May 2024. The analyses included studies performed from the date 2000 until now because the contradiction of guidelines for lipid profile testing appeared for the first time in this period. A planned internal validity evaluation was performed using the National Institute of Health (NIH) quality measurement tools for observational cohort, case‒control, controlled interventional, and cross-sectional studies. The data were synthesized according to RevMan 5.3. Results Eight studies with a total of 244,665 participants were included. The standardized mean difference in cholesterol in six studies showed significant differences in overall effect among fasting and nonfasting states (P

Dates are essential fruits loaded with vital nutrients that keep bones healthy and prevent bone-related disorders. Approximately 8.46 million tons of different types of dates are cultivated and produced annually around the globe. There are more than 400 types of dates that are time-consuming and expensive to produce. Classifying them using conventional methods is labor-intensive, and this is one of the biggest problems for the date industry. Dataset fruit classification plays a vital role in the food industry. Dates can be classified from a luxury class to a less quality class. Accordingly, the food industry needs an automotive date fruit classifier that can work in food factories. This study proposes a pioneering method to classify date fruit that relies on extracting features from the texture of dates using Scattering Wavelet Transformation (SWT). The SWT yields in numeric coefficients were found to be immune to the deformation of invariants. This feature set trains an ensemble classifier that combines a voting mechanism to eliminate overfitting. The ensemble classifier consists of a random forest, a support vector machine classifier, and a logistic regression hyper-learner. Our novel approach was tested on two benchmarked datasets. The first data set scored F1 between 0.95 and 1.0 at the same time. The second dataset registered F1 between 0.96 and 1.0 in each of the 20 date classes. Some dates are close to each other in texture, resulting in high false positives or recall, causing a lower F1 score accuracy degree. The novelty of this approach comes from the featured representative of each date class, relying on the texture of the fruit as a discriminative feature, not on the fruit shape or color, which may not be robust enough as distinguishable features, especially in date classes that are close to each other in shape. Doi: 10.28991/HIJ-2024-05-02-010 Full Text: PDF

Abstract Statins are used to reduce liver cholesterol levels but also carry a dose‐related risk of skeletal muscle toxicity. Concentrations of statins in plasma are often used to assess efficacy and safety, but because statins are substrates of membrane transporters that are present in diverse tissues, local differences in intracellular tissue concentrations cannot be ruled out. Thus, plasma concentration may not be an adequate indicator of efficacy and toxicity. To bridge this gap, we used physiologically based pharmacokinetic (PBPK) modeling to predict intracellular concentrations of statins. Quantitative data on transporter clearance were scaled from in vitro to in vivo conditions by integrating targeted proteomics and transporter kinetics data. The developed PBPK models, informed by proteomics, suggested that organic anion–transporting polypeptide 2B1 (OATP2B1) and multidrug resistance–associated protein 1 (MRP1) play a pivotal role in the distribution of statins in muscle. Using these PBPK models, we were able to predict the impact of alterations in transporter function due to genotype or drug–drug interactions on statin systemic concentrations and exposure in liver and muscle. These results underscore the potential of proteomics‐guided PBPK modeling to scale transporter clearance from in vitro data to real‐world implications. It is important to evaluate the role of drug transporters when predicting tissue exposure associated with on‐ and off‐target effects.

A complex system of neural pathways, collectively known as the microbiota–gut–brain (MGB) axis, interconnects the gut microbiota, the gastrointestinal system, and the brain along with its periphery. Previous studies have demonstrated that modulation of the MGB axis can influence stress-related behaviors such as anxiety. This connection becomes apparent in scenarios like agonistic behavior in laying hens, which is characterized by aggressive head and feather pecks, that can ultimately result in cannibalism and death. The objective was to examine the effects of a dietary synbiotic on agonistic behavior, plasma and brain monoamines, stress parameters, and cecal microbiota counts via modulation of the MGB axis. A total of 396 W36 Hy-Line laying hens were provided at random with a control (CON: basal diet) or treatment (SYN: basal diet supplemented with synbiotic) diet from 50 to 60 weeks old (nine pens/treatment, 22 birds/pen). Blood samples and video recordings (three consecutive days/week) were taken at 50 and 60 weeks. At 60 weeks, three hens/pen were euthanized for brain and cecal microbiota collection. Threatening, fighting, head, body, and feather pecking all occurred less frequently at 60 weeks in the SYN group (p < 0.05). Plasma corticosterone, adrenocorticotropic hormone, dopamine, and serotonin were significantly lower while tryptophan and 5-hydroxyindoleacetic acid were significantly higher in birds from the SYN group (p < 0.05). Significant differences in serotonin, 5-hydroxyindoleacetic acid, dopamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid were observed in the hypothalamus, hippocampus, and amygdala of the brain. Serotonin and dopamine turnover rates were significantly different in all three regions of the brain (p < 0.05). Cecal counts of Lactobacillus and Bifidobacterium were significantly higher in the SYN group (p < 0.05). Synbiotic supplementation resulted in many significant differences, indicating activation of the serotonergic systems and modulation of both the MGB axis and HPA axis with positive effects on welfare and stress.

Introduction The use of e-cigarettes (ECs) has reached unprecedented levels, due to a variety of reasons, including the misconception regarding their safety. Thus, there have been efforts to characterize the effects of EC exposure, including in the context of thirdhand EC (THEC) on a host of disorders, such as cardiovascular disease (CVD). Methods To address this issue, we sought to characterize the effects of THEC on platelet function and thrombus formation, using a novel mouse exposure protocol that resembles real life scenarios. To assess these effects, a host of related in vivo (i.e. tail bleeding time, and ferric chloride injury induced thrombosis model) assays and in vitro platelet specific (e.g. aggregation, and dense granule secretion) investigative assays were conducted. Results Our in vivo characterization demonstrated that THEC exposed mice exhibited a prothrombotic phenotype reflected by their shortened tail bleeding (THEC: 37 ± 15 seconds, versus clean air: 183 ± 56 s) and occlusion times (THEC: 188 ± 39 s, versus clean air: 519 ± 70 s), relative to those exposed to clean air. Importantly, we found no difference in the platelet counts between the THEC and clean air mice. As for the underlying mechanism, separate experiments revealed significantly enhanced platelet aggregation, dense and alpha granule secretion, as well as integrin/GPIIb-IIIa activation and phosphatidylserine exposure in response to thrombin and ADP agonist stimulation. Conclusions Taken together, these results provide evidence that THEC does have the capacity to increase the risk of thrombotic disease, which should increase awareness regarding its underappreciated negative health effects.

While telemedicine has shown promise for diagnosis and treatment, its integration into specialised clinics and mainstream healthcare is slow. A study at Sultan Qaboos University Hospital, Oman, investigated parental perceptions of virtual clinics and telemedicine experiences among parents of children with neurodevelopmental disorders (NDD) conducted from January 2021 to January 2022; the cross-sectional study involved 130 participants. The study revealed that 70% of participants were male, and the mean age of the children was 6.1 ± 0.26 years. Regarding telemedicine awareness, 53% of respondents were informed, yet encountered obstacles such as poor internet service and lack of awareness. Despite challenges, 46% of respondents viewed telemedicine positively. Parents showed significant differences in their perception of virtual interviews based on interview purpose (P = 0.034), clinic type (P

Quantum computers (QCs) aim to disrupt the status-quo of computing – replacing traditional systems and platforms that are driven by digital circuits and modular software – with hardware and software that operate on the principle of quantum mechanics. QCs that rely on quantum mechanics can exploit quantum circuits (i.e., quantum bits for manipulating quantum gates) to achieve ‘quantum computational supremacy’ over traditional, i.e., digital computing systems. Currently, the issues that impede mass-scale adoption of quantum systems are rooted in the fact that building, maintaining, and/or programming QCs is a complex and radically distinct engineering paradigm when compared to the challenges of classical computing and software engineering. Quantum service orientation is seen as a solution that synergises the research on service computing and quantum software engineering (QSE) to allow developers and users to build and utilise quantum software services based on pay-per-shot utility computing model. The pay-per-shot model represents a single execution of instruction on quantum processing unit and it allows vendors (e.g., Amazon Braket) to offer their QC platforms, simulators, and software services to end-users. This research contributes by (i) developing a reference architecture for enabling Quantum Computing as a Service (QCaaS), (ii) implementing microservices with the quantum-classic split pattern as an architectural use-case, and (iii) evaluating the architecture based on practitioners’ feedback. The proposed reference architecture follows a layered software pattern to support the three phases of service lifecycle namely development, deployment, and split of quantum software services. In the QSE context, the research focuses on unifying architectural methods and service-orientation patterns to promote reuse knowledge and best practices to tackle emerging and futuristic challenges of architecting QCaaS.

Purpose: To evaluate the association of sickle-cell disease (SCD) and sickle-cell trait (SCT) disease with diabetic retinopathy (DR) in patients with diabetes mellitus (DM). Design: Population-based, retrospective cohort study utilizing data from the TriNetX Research Network, including 119 million patients across 80 health care organizations worldwide. Participants: Diabetes mellitus patients (type 1 [T1DM] or 2 [T2DM]), with or without SCD and SCT, were included. Three cohorts were analyzed, including (1) DM patients without SCD, SCT, or sickle-cell/hemoglobin-C; (2) DM with SCD; and (3) DM with SCT. Methods: All patients with DM were categorized into 3 cohorts based on the presence of SCD and SCT. Each cohort underwent 1:1 propensity score matching for demographics, blood glucose levels, hemoglobin A1C, and other relevant comorbidities. Main Outcome Measures: Risk of DR in DM patients with and without SCD or SCT. Results: There was no significant difference in the risk of any T1DR between those with and without SCD. However, for those with SCT, there was a notable twofold increased risk for T1-proliferative DR (PDR) (relative risk [RR]: 2.03; 95% confidence interval [CI]: 1.33–3.01). In contrast, there was an elevated risk for any T2DR in patients with SCD (RR: 1.50; 95% CI: 1.19–1.88), particularly due to higher PDR risks in T2DM patients (RR: 1.83; 95% CI: 1.29–2.60). The risk of mild to moderate T2DM non-PDR was also found to be higher in patients with SCT. Conclusions: The risk of any DR was increased in T2DM patients with SCD or SCT, with increased risks for PDR in patients with SCT and T1DM. This indicates there may be a potential role of sickle-cell disorders in diabetic eye disease progression. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Approximately 71 million people worldwide are supposed to have chronic hepatitis C virus (CHCV). New direct-acting antiviral (DAA) medications have been used, which helped successfully in complete treatment of CHCV and achieved a sustained virological response (SVR). However, some patients may acquire HCV resistance to DAAs, which may result in treatments failure. The aim of the present study was to compare among the patients that were experiencing virologic relapse (VR) and SVR in relation to the patterns of NS5A and NS5B genes resistance associated substitutions (RASs) in the chronic HCV infected Egyptian patients, who received Sofosbuvir (SOF) and Daclatasvir (DCV) combination therapy. All patients that were infected by chronic HCV had completed treatment with SOF and DCV combination therapy and were followed up after the end of this treatment. A total of 10 out of 100 serum specimens were collected from the enrolled patients and analyzed, where two and eight specimens were representatives for VR and SVR, respectively. These samples had undergone reverse transcriptase-polymerase chain reaction amplification (RT-PCR) of NS5A and NS5B genes, partially sequenced by the Sanger method, and then analyzed phylogenetically to determine their genetic subtypes and RASs. Finally, SVR was gained in all but two patients who were experiencing VR that carried natural NS5A-RASs at positions L31M and Y93H. They were considered as significant for DCV resistance as well as natural NS5B-RASs (T282S), which represented the main polymorphism for SOF resistance. In this study, a number of mutational combinations in the analyzed NS5A and NS5B genes were identified, which may increase the risk of treatments failure in the patients administered regimens including multiple DAA, compared to the baseline sequences of those patients that were experiencing SVR.

Abstract More focus has recently been placed on enhancing the strength, elastic modulus, coefficient of thermal expansion (CTE), wear and corrosion resistance, and other qualities of aluminum (Al) alloys by varying the quantity of ceramics added for a range of industrial uses. In this regard, Al-4.2-Cu-1.6Mg matrix nanocomposites reinforced with nano-ZrO2 particles have been created using the powder metallurgy approach. The microstructure and particle size distributions of the produced powders were analyzed using a diffraction particle size analyzer, XRD, TEM, and SEM. To achieve good sinterability, the powders were compacted and sintered in argon. The sintered nanocomposites' mechanical, elastic, and physicochemical characteristics were measured. Additionally, the behavior of corrosion, wear, and thermal expansion were examined. The results showed a decrease in the particle sizes of the Al-Cu-Mg alloy by adding ZrO2 nanoparticles up to 45.8 nm for the composite containing 16 wt.% ZrO2. By increasing the sintering temperature to 570 °C, the densification of nanocomposites was enhanced. Also, the coefficient of thermal expansion and wear rate remarkably decreased by about 28 and 37.5% by adding 16 wt.% ZrO2. Moreover, microhardness yield, strength, and Young’s modulus were enhanced to 161, 145, and 64%, respectively, after adding 16 wt.% ZrO2. In addition, increasing the exposure time was responsible for decreasing the corrosion rate for the same sample.

Abstract Background Newcastle Disease Virus (NDV) causes severe economic losses in the poultry industry worldwide. Hence, this study aimed to discover a novel bioactive antiviral agent for controlling NDV. Streptomyces misakiensis was isolated from Egyptian soil and its secondary metabolites were identified using infrared spectroscopy (IR), gas chromatography–mass spectrometry (GC–MS), and nuclear magnetic resonance (NMR) spectroscopy. The inhibitory activity of bioactive metabolite against NDV were examined. Three experimental groups of 10-day-old specific pathogen-free embryonated chicken eggs (SPF-ECEs), including the bioactive metabolite control group, NDV control positive group, and α-sitosterol and NDV mixture-treated group were inoculated. Results α-sitosterol (Ethyl-6-methylheptan-2-yl]-10,13-dimethyl-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol), a secondary metabolite of S. misakiensis, completely inhibited hemagglutination (HA) activity of the NDV strain. The HA activity of the NDV strain was 8 log2 and 9 log2 for 0.5 and 0.75% RBCs, respectively. The NDV HA activity for the two concentrations of RBCs was significantly (P

This study introduces an innovative approach to address the growing challenge of detecting and distinguishing ChatGPT-generated content within scientific articles, particularly in the context of Learning Management Systems (LMS). Leveraging state-of-the-art large language models, including Robustly Optimized BERT Pretraining (RoBERTa), Text-to-Text Transfer Transformer (T5), and Generative Pre-trained Transformers (EleutherAI GPT-Neo-125M), our methodology focuses on the incorporation of the LMS concept into the research framework. To construct a comprehensive dataset representative of the diverse landscape of scientific abstracts, samples of the dataset are gathered from articles produced by human authors and those generated by ChatGPT within the LMS framework. The models (RoBERTa, T5, and EleutherAI GPT-Neo-125M) were subsequently trained on this unique dataset, showcasing their adaptability to the distinct characteristics of both human-generated and AI-generated content within the LMS context. The efficacy of our approach was rigorously evaluated using a range of metrics, resulting in an outstanding accuracy exceeding 99%. This achievement underscores the robustness of our methodology in successfully discerning content generated by ChatGPT within the LMS and that authored by human contributors, thereby advancing the field of content differentiation in scientific discourse.

In this paper, a second order hyperbolic traffic model is proposed to assess the impact of potholes on traffic evolution. The driver presumption to potholes considers the safe time headway, change in velocity and the changes in potholes width. Further, the traffic alignment is based on the driver reaction to potholes, distance headway and size of potholes. The changes in traffic evolution travel at or below traffic velocity. This rate of changes is impacted by the potholes size, driver reaction, distance headway, time headway and the changes in velocity distributions. Furthermore, the direction of travel during congestion is rearwards, while is in forward direction during smooth flow. The model proposed in this paper can be employed for traffic density below and beyond the critical density. The Gabriel et al. model considers a constant for driver presumptions and is more a fitting parameter, rather than a traffic parameter. This is an inappropriate methodology to employ driver presumptions in second order traffic systems. The Gabriel et al. traffic system is based on the uniform constant velocity for different road conditions, which characterizes traffic evolution unrealistically. The proposed and Gabriel et al. traffic models are assessed over a 4000 m road for changes in the width of a pothole. Both the Gabriel et al. and proposed traffic models are numerically implemented with the conservative scheme in Matlab. The discretization stability of both the models is enforced with the Courant, Friedrich and Levy (CFL) condition. With smaller width of the pothole, the changes in upstream traffic are minor, and the density evolution in forward direction is smoother. While, with larger width of the pothole, the density evolution is slower, resulting congestion in the upstream, and exists for longer period. Moreover, Segment Travel Time (STT) is assessed subject to various sizes of a pothole, and it is observed that the STT significantly increases with the increase in pothole size. Conversely, the Gabriel et al. model characterizes traffic inadequately subject to various sizes of the pothole. The density behavior with this model is almost uniform, thus limiting its performance. The simulation results showed that the traffic evolution with the proposed model is more appropriate than with the Gabriel et al. model.

Global dissemination of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB) such as carbapenemase-producing Enterobacterales has resulted in reviving colistin as a final therapeutic alternative. Colistin resistance foretold a catastrophe. We aimed to detect the rates of carbapenems and colistin resistance among hospital-acquired Enterobacterales species, verify the underlying mechanisms and provide antibiogram for colistin-resistant isolates. The collected Enterobacterales isolates were tested for their antimicrobial susceptibility by the disk diffusion method and agar dilution was utilized for both imipenem and colistin. The production of ESβLs and carbapenemases was phenotypically assessed by the combined disk (CDT) and modified carbapenem inactivation (mCIM) tests, respectively. Possible attributes for colistin resistance were explored by detection of both plasmid- and efflux pump-mediated mechanisms. By multiplex PCR assay, carbapenem resistance (blaNDM-1 & blaOXA-48) and mobilized colistin-resistant-1 (mcr-1) genes were identified. A total of 160 Enterobacterales isolates were obtained of which 68.8% were MDR, 25% were XDR and 6.3% were pandrug-resistant (PDR) isolates with no statistically significant difference among Enterobacterales species (P> 0.05). Carbapenems resistance was detected in 41.3% (66/160) while colistin resistance was detected in 22% (36/160) of isolates. Proteus mirabilis expressed the highest rate of colistin resistance (100%; 16/16), followed by Enterobacter aerogenes (23.1%; 6/26), E. coli (13%; 6/46) and K.pneumoniae (11.1%; 8/72). One hundred percent (36/36) of colistin-resistant isolates proved efflux pump activity for colistin. However; only 2% (2/100) of tested Enterobacterales carried mcr-1 gene through molecular analysis. Colistin-resistant isolates exhibited variable susceptibility to the tested antimicrobial agents of which fosfomycin was the highest (94.1%). Efflux pump activity played a major role for colistin resistance among Enterobacterales species and fosfomycin could be a promising therapeutic option.

We compared the outcomes of various concentrations of Cinnamomum verum bark powder (CNP), a natural product, to a conventional anticoccidial drug in induced Eimeria tenella infection in broilers aged 21 days. On day 21, 250 birds (Ross 308) were randomly assigned to one of 10 treatments, five of which had Eimeria tenella infection and five of which did not. Results 14 days post-infection (dpi) revealed that the treatments had a significant effect on body weight gain (BWG) and production efficiency factor (PEF). Although the 2 g CNP and Salinomycin (Sacox) treatments performed equally well, the 2 g CNP had the highest BWG and PEF under challenging conditions. Although the PEF improved satisfactorily at 14 dpi, the loss of BWG at 7 dpi did not compensate at 14 dpi. Challenged birds had longer and heavier small intestines, atrophiedceca, lower creatinine levels and higher eosinophils % than unchallenged birds. The elevation lesion score and oocyst secretion of challenged birds decreased with increasing cinnamon dosage. In conclusion, 6 g CNP as a natural product could be as effective as Sacox against occidiosis, with 2 g CNP performing best at 14 dpi. However, more research is required to fully understand its anticoccidial mechanisms.HighlightsCinnamomum verum bark may benefit broiler health by reducing Eimeria tenella oocysts.Under coccidial challenge, Cinnamomum verum bark at 2 g/kg diet may improve broiler body weight gain and production efficiency at 34 days of age (14 days post-infection).The lesion score and oocyst secretion of challenged birds decreased less as cinnamon dosage was increased.

The study area was classified into three categories (vegetation cover, water, and others)using four satellite images of the Landsat 8 satellite captured during March for the period 2019-2022 into. The results showed that there is a change in the climatic conditions (temperature and rainfall) for the years of the study. The average temperature increased from 12.29°C to 25.967°C from the year 2019 to 2022. The annual amount of precipitation was decreased from 469.43 mm for the year 2019 to 105.49 mm for the year 2022.this negatively changed affected the water and agricultural resources, as the amount of water storage for Lake Hamrin and Lake Al-Wand together reached to 2,314,584,000 m3 and 40,404,000 m3 for the years 2019 and 2022, respectively. This led to decrease in the vegetation area from 1587.29 km2 to 356.17 for the year 2019 km2 and 2022, respectively.

Introduction It is well documented that cardiovascular disease (CVD) is the leading cause of death in the US and worldwide, with smoking being the most preventable cause. Additionally, most smokers die from thrombotic-based diseases, in which platelets play a major role. To this end, because of the proven harm of smoking, several novel tobacco products such as electronic(e)-waterpipe have been gaining popularity among different sectors of the population, partly due to their “false” safety claims. While many investigators have focused on the negative health effects of traditional cigarettes and e-cigarettes on the cardiovascular system, virtually little or nothing is known about e-waterpipes, which we investigated herein. Methods and Materials To investigate their occlusive CVD effects, we employed a whole-body mouse exposure model of e-waterpipe vape/smoke and exposed C57BL/6J male mice (starting at 7 weeks of age) for 1 month, with the controls exposed to clean air. Exposures took place seven times a week, according to the well-known Beirut protocol, which has been employed in many studies, as it mimics real-life waterpipe exposure scenarios; specifically, 171 puffs of 530 ml volume of the e-liquid at 2.6 s puff duration and 17 s puff interval. Results The e-waterpipe exposed mice had shortened bleeding and occlusion times, when compared to the clean air controls, indicating a prothrombotic phenotype. As for the mechanism underlying this phenotype, we found that e-waterpipe exposed platelets exhibited enhanced agonist-triggered aggregation and dense granule secretion. Also, flow cytometry analysis of surface markers of platelet activation showed that both P-selectin and integrin GPIIb-IIIa activation were enhanced in the e-waterpipe exposed platelets, relative to the controls. Finally, platelet spreading and Akt phosphorylation were also more pronounced in the exposed mice. Conclusion We document that e-waterpipe exposure does exert untoward effects in the context of thrombosis-based CVD, in part, via promoting platelet hyperreactivity.

Abstract Background In this meta-analysis, we aimed to update the clinical evidence regarding the efficacy and safety of TXA in the prevention of PPH. Methods A literature search of PubMed, Scopus, Web of Science, Google Scholar, and Cochrane Library from inception until December 2022 was conducted. We included randomized controlled trials (RCTs) comparing TXA with a placebo among pregnant women. All relevant outcomes, such as total blood loss, the occurrence of nausea and/or vomiting, and changes in hemoglobin, were combined as odds ratios (OR) or mean differences (MD) in the meta-analysis models using STATA 17 MP. Results We included 59 RCTs (18,649 patients) in this meta-analysis. For cesarean birth, TXA was favored over the placebo in reducing total blood loss (MD= -2.11 mL, 95%CI [-3.09 to -1.14], P

Pd(II) with the Schiff base ligand 2-Hydroxy-3-Methoxy Benzaldehyde-Thiosemicarbazone (HMBATSC) (L2) and 2-aminobenzothiazole (2-ABZ) (L1) was synthesized. The Schiff base ligand and the Palladium(II) complex were characterized by C.H.N.S, FT-IR, conductance studies, magnetic susceptibility, XRD, and TGA. From the elemental analysis and spectral data, the complex was proposed to have the formula [Pd(HMBATSC)(2-ABZ)H2O]. The interaction between the Pd(II) complex and DNA was examined through various methods, including UV–Vis spectroscopy, fluorescence techniques, and DNA viscosity titrations. The findings provided strong evidence that the interaction between the Pd(II) complex and DNA occurs through the intercalation mode. The analysis yielded the following values: a Stern–Volmer quenching constant (ksv) of 1.67 × 104 M−1, a quenching rate constant (kq) of 8.35 × 1011 M−1 s−1, a binding constant (kb) of 5.20 × 105 M−1, and a number of binding the sites (n) of 1.392. DFT studies suggest that the azole derivative may act as an electron donor through pyridine nitrogen, while the Schiff base ligand may act as an electron donor via oxygen and sulfur atoms. TDDFT calculations indicate that the intramolecular charge transfer from the Schiff base to Pd(II) is responsible for the complex’s fluorescence quenching. The powder X-ray diffraction data revealed that the complex is arranged in a monoclinic system. The resulting Pd(II) complex was investigated for its antimicrobial activity and demonstrated antibacterial efficiency. Interestingly, it showed potent activity against E. coli and E. niger that was found to be more powerful than that recorded for Neomycin.

Abstract Background Although currently most widely used in mechanical ventilation and cardiopulmonary resuscitation, features of the carbon dioxide (CO2) waveform produced through capnometry have been shown to correlate with V/Q mismatch, dead space volume, type of breathing pattern, and small airway obstruction. This study applied feature engineering and machine learning techniques to capnography data collected by the N-Tidal™ device across four clinical studies to build a classifier that could distinguish CO2 recordings (capnograms) of patients with COPD from those without COPD. Methods Capnography data from four longitudinal observational studies (CBRS, GBRS, CBRS2 and ABRS) was analysed from 295 patients, generating a total of 88,186 capnograms. CO2 sensor data was processed using TidalSense’s regulated cloud platform, performing real-time geometric analysis on CO2 waveforms to generate 82 physiologic features per capnogram. These features were used to train machine learning classifiers to discriminate COPD from ‘non-COPD’ (a group that included healthy participants and those with other cardiorespiratory conditions); model performance was validated on independent test sets. Results The best machine learning model (XGBoost) performance provided a class-balanced AUROC of 0.985 ± 0.013, positive predictive value (PPV) of 0.914 ± 0.039 and sensitivity of 0.915 ± 0.066 for a diagnosis of COPD. The waveform features that are most important for driving classification are related to the alpha angle and expiratory plateau regions. These features correlated with spirometry readings, supporting their proposed properties as markers of COPD. Conclusion The N-Tidal™ device can be used to accurately diagnose COPD in near-real-time, lending support to future use in a clinical setting. Trial registration: Please see NCT03615365, NCT02814253, NCT04504838 and NCT03356288.

Conclusion: Endogenous fungal endophthalmitis is most commonly seen in immunocompromised patients, and oral corticosteroid therapy for such patients should be used with caution as it can worsen an infection. In cases of fusarial endophthalmitis, visual prognosis is poor.

Olive is an essential industrial crop in the Mediterranean region with valuable economic and agricultural concerns. Despite its drought resistance, its productivity is restricted by extreme drought stress. Olive cultivars display considerable variation in response mechanisms to drought stress. Accordingly, the impact of mild and extreme water deprivation over two seasons compared to full irrigation requirements on growth and physiological characteristics of three diverse olive cultivars. Three olive cultivars, ‘Manzanillo’, ‘Eggizi-Shami’, and ‘Tofaahi’, were evaluated under three irrigation regimes 100% ETc, 75% ETc, and 50% ETc. Characteristics of shoot and root, as well as physio-chemical constituents, were determined. Besides, the gene expression of dehydration-responsive element binding (DREB), dehydrin (DHN), and catalase (CAT) genes in olive cultivars were explored under different irrigation regimes. The results indicated a substantial impact of irrigation level on all studied parameters. The mild and extreme drought stress treatments caused a gradual reduction in nitrogen, phosphorus, and potassium content, relative water content, root and shoot length, root and leaf numbers, branch count, and leaf area across both seasons. Conversely, proline content was considerably increased under drought treatments compared to well-watered conditions. Similarly, the assessed cultivars exhibited significant variation in all studied parameters, with ‘Eggizi-Shami’ demonstrating superiority. Under mild and extreme drought stress conditions, the cultivar ‘Eggizi-Shami’ displayed the highest proline content and most growth characteristics. Besides, the real-time quantitative PCR (RT-qPCR) analysis displayed significant alterations in gene expression of the tested three genes related to drought response (DHN, DREB, and CAT). The RT-qPCR analysis revealed that under drought stress conditions (75% and 50% ETc), ‘Eggizi-Shami’ exhibited higher expression compared to the other two cultivars (‘Tofaahi’ and ‘Manzanillo’). Combining the results of morphological and physiological parameters with gene expression analysis of drought-related genes can offer highly validated information about drought-tolerant olive cultivars. This integrated approach serves as an innovative methodology to identify and confirm genes involved in abiotic stress.

Hexahydroquinoline (HHQ) scaffold was constructed and recruited for development of new series of anticancer agents. Thirty-two new compounds were synthesised where x-ray crystallography was performed to confirm enantiomerism. Thirteen compounds showed moderate to good activity against NCI 60 cancer cell lines, with GI % mean up to 74% for 10c. Expending erlotinib as a reference drug, target compounds were verified for their inhibiting activities against EGFRWT, EGFRT790M, and EGFRL858R where compound 10d was the best inhibitor with IC50 = 0.097, 0.280, and 0.051 µM, respectively, compared to erlotinib (IC50 = 0.082 µM, 0.342 µM, and 0.055 µM, respectively). Safety profile was validated using normal human lung (IMR-90) cells. 10c and 10d disrupted cell cycle at pre-G1 and G2/M phases in lung cancer, HOP-92, and cell line. Molecular docking study was achieved to understand the potential binding interactions and affinities in the active sites of three versions of EGFRs.

New pyrrolidine derivatives with more than 50% structural similarity with captopril were designed to get new captopril mimics with superior potential to act on both peripheral and central ACE. Further optimization was carried out through pharmacophoric mapping, then pharmacokinetics of these compounds were analyzed, 42 derivatives were selected for further study, as they exhibited potential to pass through BBB. Molecular docking on ACE using captopril and lisinopril as reference drugs was performed, and Compound 28 (2-Pyrrolidin-2-ylidene-N-thiomorpholin-4-ylmethyl-malonamic acid ethyl ester) showed the best docking scores, proving its superiority over captopril and comparability to lisinopril. Further molecular dynamics simulations and energy calculations demonstrated binding stability and close mimicry to both drugs. The results indicate that Compound 28 is a promising candidate for further investigations as a potential drug to act centrally and peripherally. Compound 28 can be synthesized by reacting Cyano-pyrrolidin-2-ylidene-acetic acid ethyl ester through Mannich reaction with thiomorpholine and formaldehyde.

ABSTRACTA library of natural sesquiterpene and phenolic compounds from Petasites japonicus are being investigated through different computational techniques to study their ability to target BMP. Lipinski rule, ADMET, molecular docking studies and metabolism were used to reach promising candidates with proposed activity against BMP. Four sesquiterpenes (kablicin, petisinol, bakkenolide D and bakkenolide IIIa) and four phenolic compounds exhibited drug-like properties (caffeic acid, petasiphenol, petasitesin A and petasitesin B), so they deserve further clinical exploration as bone loss modulators. The phenolic compounds specially fukinolic acid and petasiphenol showed lower binding energy with both BMPRIA and BMPRII than Icariin agonist and sesquiterpenes. Bakkenolide IIIa showed dual potential on both BMPRIA and BMPRII with binding energies equal – 7.82 and – 9.9 Kcal/mol respectively, which is more better score than Betulinic acid agonist. This research is focusing on plant-human interactions and exploring the ability of plant constituents to modulate a human protein such as BMP.

Nano-structured lipid carriers containing zopiclone were prepared as a targeted drug delivery system to convey zopiclone directly to brain via nasal route. Nano-structured lipid carriers were constructed adopting hot emulsification-ultrasonication method using palmitic acid in place of the solid lipid, cod liver oil as liquid lipid, and poloxamer 407 as a surfactant. A three-factor three-level central composite face-centered design was used to optimize the formulated nano-structured lipid carriers. The independent factors were lipid amount (X1), surfactant amount (X2), and sonication time (X3). The examined responses were entrapment efficiency (EE,Y1,%), particle size (PS,Y2,nm), zeta potential(mV), polydispersity index(PDI,Y3), in vitro release(Q8h,Y4,%) and dissolution efficiency (DE,Y5,%). The optimum formula showed high entrapment efficiency of 94.31% ± 2.44, in vitro drug release of 83.89% ± 1.77 with dissolution efficiency equals 88.63% ± 2.01, small particle size of 71.27 nm ± 13.57 and low polydispersity index 0.097 ± 0.15. In vivo biodistribution in mice was evaluated by a radiobiological technique using radioiodinated zopiclone([131I]iodo-ZP). Results revealed the superiority of the intranasal route to deliver zopiclone directly to brain faster and higher brain uptake (6.9 ± 1.02%ID/g at 5 min post-administration). The current study confirmed that intranasal administration of nano-structured lipid carriers had great potential as an effective tool for targeted brain zopiclone delivery for insomnia treatment.

Abstract Background To compare the microvascular features of different subtypes of diabetic macular edema (DME) by optical coherence tomography angiography (OCTA). Methods A cross-sectional study including treatment-naive patients with DME. Eyes were divided according to optical coherence tomography determined morphology into two groups: cystoid macular edema (CME) and diffuse retinal thickening (DRT), with further subdivision according to the presence of subretinal fluid. All patients underwent 3 × 3 and 6 × 6 mm OCTA scans of the macula to compare the foveal avascular zone (FAZ) area, vascular density (VD) of the superficial (SCP) and deep (DCP) capillary plexus and choriocapillaris flow (CF). Laboratory findings (HbA1C and triglyceride levels) were also correlated with the OCTA findings. Results The study included 52 eyes, 27 had CME and 25 had DRT. There were no significant differences between the VD of the SCP (p = 0.684) and DCP (p = 0.437), FAZ of SCP (p = 0.574), FAZ of DCP (p = 0.563) and CF (p = 0.311). Linear regression analysis revealed that DME morphology was the strongest predictor for BCVA. Other significant predictors included HbA1C and triglyceride levels. Conclusion The morphology of DME, irrespective of SRF, was most significantly correlated with BCVA in treatment-naive patients and CME subtype could be an independent predictor of poor BCVA in patients with DME.

The potential health benefits of phytochemicals in preventing and treating diseases have gained increasing attention. Here, we proved that the methylated isoflavone prunetin possesses a reno-therapeutic effect against renal ischemia/reperfusion (I/R) insult by activating G protein-coupled receptor 30 (GPR30). After choosing the therapeutic dose of prunetin against renal I/R injury in the pilot study, male Sprague Dawley rats were allocated into 5 groups; viz., sham-operated (SO), SO injected with 1 mg/kg prunetin intraperitoneally for three successive days, untreated I/R, I/R treated with prunetin, and I/R treated with G-15, the selective GPR30 blocker, followed by prunetin. Treatment with prunetin reversed the I/R renal injury effect and majorly restored normal renal function and architecture. Mechanistically, prunetin restored the I/R-induced depletion of renal GPR30, an impact that was canceled by the pre-administration of G-15. Additionally, post-administration of prunetin normalized the boosted inflammatory markers indoxyl sulfate, TLR4, and TRIF and abrogated renal cell demise by suppressing necroptotic signaling, verified by the inactivation of p-RIPK1, p-RIPK3, and p-MLKL while normalizing the inhibited caspase-8. Besides, prunetin reversed the I/R-mediated mitochondrial fission by inhibiting the protein expression of PGMA5 and p-DRP-1. All these favorable impacts of prunetin were nullified by G-15. To sum up, prunetin exhibited a significant reno-therapeutic effect evidenced by the enhancement of renal morphology and function, the suppression of the inflammatory cascade indoxyl sulfate/TLR4/TRIF, which turns off the activated/phosphorylated necroptotic trajectory RIPK1/RIPK3/MLKL, while enhancing caspase-8. Additionally, prunetin opposed the mitochondrial fission pathway RIPK3/PGMA5/DRP-1, effects that are mediated via the activation of GPR30.

A parametric study is conducted using the finite element method to investigate the bearing capacity and the associated failure mechanisms of strip footings on top of slope with cohesionless soil. The developed and validated numerical model was used to analyze 57 slopes with different design parameters, footing dimensions, and soil properties. Findings of the study quantified the variations in bearing capacity due to changes in setback distance, internal friction and dilatancy angles, footing embedment depth, and footing width. The observed variations in failure mechanisms are used to explain the behavior and stability of slope-footing system. A multilinear equation is developed to predict the bearing capacity of the footing on the top of slope based on the slope-footing design parameters and Meyerhof bearing capacity equation. The developed equation was able to predict the bearing capacity of a footing on slope with reasonable accuracy.

Road Pavement Condition Monitoring (RPCM) is indispensable for proactive maintenance, especially amidst increasing traffic and unpredictable weather patterns. The demand for cost-efficient solutions leveraging emerging technologies such as the Internet of Things (IoT), Machine Learning (ML), and cloud computing is increasing. This work examines the evolution of RPCM solutions, examines the challenges, and proposes future improvements. An extensive literature review is presented which exposes the challenges with existing RPCM solutions. The assessment criteria are the sensory platform, algorithms employed, detected road deformities, and performance. The approaches employed in RPCM are examined including their advantages and limitations. A holistic assessment of RPCM methodologies is presented which includes threshold, dynamic time warping, computer vision, and ML approaches. It is determined that smartphone-based monitoring solutions incorporating data acquisition and ML are superior to other methods. Future research directions are presented considering the limitations of existing solutions and the goal of cost-effective and efficient RPCM solutions.

Cyber security confronts a tremendous challenge of maintaining the confidentiality and integrity of user’s private information such as password and PIN code. Billions of users are exposed daily to fake login pages requesting secret information. There are many ways to trick a user to visit a web page such as, phishing mails, tempting advertisements, click-jacking, malware, SQL injection, session hijacking, man-in-the-middle, denial of service and cross-site scripting attacks. Web spoofing or phishing is an electronic trick in which the attacker constructs a malicious copy of a legitimate web page and request users’ private information such as password. To counter such exploits, researchers have proposed several security strategies but they face latency and accuracy issues. To overcome such issues, we propose and develop client-side defence mechanism based on machine learning techniques to detect spoofed web pages and protect users from phishing attacks. As a proof of concept, a Google Chrome extension dubbed as PhishCatcher, is developed that implements our machine learning algorithm that classifies a URL as suspicious or trustful. The algorithm takes four different types of web features as input and then random forest classifier decides whether a login web page is spoofed or not. To assess the accuracy and precision of the extension, multiple experiments were carried on real web applications. The experimental results show remarkable accuracy of 98.5% and precision as 98.5% from the trials performed on 400 classified phished and 400 legitimate URLs. Furthermore, to measure the latency of our tool, we performed experiments over forty phished URLs. The average recorded response time of PhishCatcher was just 62.5 milliseconds.

Structured light is gaining importance in free-space communication. Classifying spatially-structured light modes is challenging in a dusty environment because of the distortion on the propagating beams. This article addresses this challenge by proposing a deep learning convolutional autoencoder algorithm for modes denoising followed by a neural network for modes classification. The input to the classifier was set to be either the denoised image or the latent code of the convolutional autoencoder. This code is a low-dimensional representation of the inputted images. The proposed machine learning (ML) models were trained and tested using laboratory-generated mode data sets from the Laguerre and Hermite Gaussian mode bases. The results show that the two proposed approaches achieve an average classification accuracy exceeding 98%, and both are better than the classification accuracy reported recently (83–91%) in the literature.

Abstract Background Trigeminal neuralgia (TGN) is a facial pain disorder often caused by arterial compression of the trigeminal nerve. Microvascular decompression (MVD) remains the most definitive treatment for this disorder, with a reported cure rate between 60 and 80%. MVD techniques often involve a retrosigmoid craniotomy with placement of an inert foreign material, such as Gore-Tex or Teflon, between the nerve and the compressing vessel. Recurrence of TGN after MVD has been associated with vessel migration and adhesion formation. In this study, we tested the use of Gore-Tex sling, fixed in place with fibrin glue to displace the compressing vessel away from the nerve. Results This is a retrospective study including 20 patients who had an MVD for treatment of idiopathic TGN where a sling of Gore-Tex was used with the application of fibrin glue to prevent dislocation of the vessel. It showed that sling MVD technique is an effective method for treatment of classic trigeminal neuralgia. Eighteen patients improved within 2 weeks postoperatively. One patient had recurrence of symptoms and was reoperated 1 year later. Conclusion Gore-Tex slinging technique is a safe simple technique for preventing re-dislocation of the offending vessel and thus recurrence of symptoms. However, larger series is needed to judge on the long-term efficacy and safety of this technique.

This study successfully used the powder metallurgy technique to produce hybrid Ti-7% Cu (vol%) matrix nanocomposites (TMNCs) reinforced with activated carbon and silica fume at reduced sintering temperatures, i.e., 1100 °C. The effect of different amounts of additives in the hybrid reinforcements on the bulk density, microstructure, mechanical properties, and wear of the nanocomposite samples thus prepared was investigated. X-ray diffraction (XRD) analysis revealed that the uniform distribution of hybrid ceramics in the nanocomposites and the formation of in situ Ti2Cu and TiC phases resulted from the interaction of Ti with both Cu and activated carbon during the milling and sintering processes, respectively. On the other hand, the values of the microhardness, ultimate strength, and longitudinal modulus of the non-reinforced sample (TS0) were 1.66 GPa, 401.20 MPa, and 172.40 GPa, respectively, which increased to 2.17 GPa, 591.25, and 256.24 GPa, respectively, for the sample containing 16 vol% of hybrid reinforcements (TS8). Finally, for the applied load of 40 N, the wear rate decreased from 0.0196 to 0.0089 mg/s with increases in the hybrid reinforcements from 0 to 16 vol%. Thus, the addition of activated carbon and silica fume can act as superb reinforcements in TMNCs.

It is tedious to machine high strength materials such as titanium alloy for making engineering products related to aerospace and medical applications due to its high corrosion resistance and low density. In this study, an endeavor was made to analyze the influence of tool electrodes in electrical discharge machining process for enhancing the machinability of Titanium α- β alloy. Copper, brass and tungsten carbide electrodes were utilized with iso energy pulse generator. It was observed that the use of copper electrode could enhance material removal mechanism due to its higher electrical conductivity. The better surface topography with tiny craters could be observed on machined specimen with tungsten carbide electrode owing to its high melting point. The IEPG generator can produce tiny craters with lower pulse energy and uniform energy distribution. Since it produces tiny crater and has higher melting point, the tungsten carbide tool electrode can create lower surface roughness than other electrodes. Brass electrode can create larger craters on the machined surface of titanium alloy specimens due to its low melting point. Hence it could create higher surface roughness and electrode wear.

New nicotinamide derivatives 6, 7, 10, and 11 were designed and synthesised based on the essential features of the VEGFR-2 inhibitors. Compound 10 revealed the highest anti-proliferative activities with IC50 values of 15.4 and 9.8 µM against HCT-116 and HepG2, respectively compared to sorafenib (IC50 = 9.30 and 7.40 µM). Compound 7 owned promising cytotoxic activities with IC50 values of 15.7 and 15.5 µM against the same cell lines, respectively. Subsequently, the VEGFR-2 inhibitory activities were assessed for the titled compounds to exhibit VEGFR-2 inhibition with sub-micromolar IC50 values. Moreover, compound 7 induced the cell cycle cessation at the cycle at %G2-M and G0-G1phases, and induced apoptosis in the HCT-116. Compounds 7 and 10 reduced the levels of TNF-α by 81.6 and 84.5% as well as IL-6 by 88.4 and 60.9%, respectively, compared to dexamethasone (82.4 and 93.1%). In silico docking, molecular dynamics simulations, ADMET, and toxicity studies were carried out.

Based on quinazoline, quinoxaline, and nitrobenzene scaffolds and on pharmacophoric features of VEGFR-2 inhibitors, 17 novel compounds were designed and synthesised. VEGFR-2 IC50 values ranged from 60.00 to 123.85 nM for the new derivatives compared to 54.00 nM for sorafenib. Compounds 15a, 15b, and 15d showed IC50 from 17.39 to 47.10 µM against human cancer cell lines; hepatocellular carcinoma (HepG2), prostate cancer (PC3), and breast cancer (MCF-7). Meanwhile, the first in terms of VEGFR-2 inhibition was compound 15d which came second with regard to antitumor assay with IC50 = 24.10, 40.90, and 33.40 µM against aforementioned cell lines, respectively. Furthermore, Compound 15d increased apoptosis rate of HepG2 from 1.20 to 12.46% as it significantly increased levels of Caspase-3, BAX, and P53 from 49.6274, 40.62, and 42.84 to 561.427, 395.04, and 415.027 pg/mL, respectively. Moreover, 15d showed IC50 of 253 and 381 nM against HER2 and FGFR, respectively.

A library of modified VEGFR-2 inhibitors was designed as VEGFR-2 inhibitors. Virtual screening was conducted for the hypothetical library using in silico docking, ADMET, and toxicity studies. Four compounds exhibited high in silico affinity against VEGFR-2 and an acceptable range of the drug-likeness. These compounds were synthesised and subjected to in vitro cytotoxicity assay against two cancer cell lines besides VEGFR-2 inhibitory determination. Compound D-1 showed cytotoxic activity against HCT-116 cells almost double that of sorafenib. Compounds A-1, C-6, and D-1 showed good IC50 values against VEGFR-2. Compound D-1 markedly increased the levels of caspase-8 and BAX expression and decreased the anti-apoptotic Bcl-2 level. Additionally, compound D-1 caused cell cycle arrest at pre-G1 and G2-M phases in HCT-116 cells and induced apoptosis at both early and late apoptotic stages. Compound D-1 decreased the level of TNF-α and IL6 and inhibited TNF-α and IL6. MD simulations studies were performed over 100 ns.

Two new series of symmetric (1a-h) and asymmetric (2a-l) 1,4-DHP derivatives were designed, synthesised, and evaluated as anticancer agents. In vitro anticancer screening of target compounds via National cancer institute “NCI” revealed that analogues 1g, 2e, and 2l demonstrated antiproliferative action with mean growth inhibition percentage “GI%” = 41, 28, and 64, respectively. The reversal doxorubicin (DOX) effects of compounds 1g, 2e, and 2l were examined and illustrated better cytotoxic activity with IC50 =1.12, 3.64, and 3.57 µM, respectively. The most active anticancer analogues, 1g, 2e, and 2l, were inspected for their putative mechanism of action by estimating their epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER-2), and Bruton’s tyrosine kinase (BTK) inhibitory activities. Furthermore, the antimicrobial activity of target compounds was assessed against six different pathogens, followed by determining the minimum inhibitory concentration “MIC” values for the most active analogues. Molecular docking study was achieved to understand mode of interactions between selected inhibitors and different biological targets.

A new series of 1H-pyrrole (6a–c, 8a–c), pyrrolo[3,2-d]pyrimidines (9a–c) and pyrrolo[3,2-e][1, 4]diazepines (11a–c) were designed and synthesised. These compounds were designed to have the essential pharmacophoric features of EGFR Inhibitors, they have shown anticancer activities against HCT116, MCF-7 and Hep3B cancer cells with IC50 values ranging from 0.009 to 2.195 µM. IC50 value of doxorubicin is 0.008 µM, compounds 9a and 9c showed IC50 values of 0.011 and 0.009 µM respectively against HCT-116 cells. Compound 8b exerted broad-spectrum activity against all tested cell lines with an IC50 value less than 0.05 µM. Compound 8b was evaluated against a panel of kinases. This compound potently inhibited CDK2/Cyclin A1, DYRK3 and GSK3 alpha kinases with 10–23% compared to imatinib (1–10%). It has also arrested the cell cycle of MCF-7 cells at the S phase. Its antiproliferative activity was further augmented by molecular docking into the active sites of EGFR and CDK2 cyclin A1.

The purpose of this study was to eliminate phosphate (P) from wastewater using MnFe2O4 nanoparticles. BET, TGA/DTG, FTIR, SEM, TEM, VSM, XRD and EDX/Map analyses were used to determine the MnFe2O4 surface properties. The specific surface area of the adsorbent was 196.56 m2/g and VSM analysis showed that the adsorbent has a ferromagnetic property. The maximum P sorption efficiency using MnFe2O4 (98.52%) was achieved at pH 6, temperature of 55 °C, P concentration of 10 mg/L, time of 60 min, and sorbent dosage of 2.5 g/L, which is a significant value. Also, the thermodynamic study indicated that the P sorption process is spontaneous and endothermic. Moreover, the utmost sorption capacity of P using MnFe2O4 was 39.48 mg/g. Besides, MnFe2O4 can be used for up to 6 reuse cycles with high sorption efficiency (>91%). Also, MnFe2O4 was able to remove phosphate, COD, and BOD5 from municipal wastewater with considerable removal efficiencies of 82.7%, 75.8%, and 77.3%, respectively.

In Iraq generally and Kurdistan region specifically, goats are an important resource for meat and milk production. It is well known that Myostatin genes (MSTN) have the essential role in growth and development due to its crucial involvement in muscle growth. The goal of this research was to reveal the polymorphism of MSTN gene in different Capra hircus breeds (native, Shami, Meriz and Kamori goat) and in wild mountain goat (Capra aegagrus) via PCR-RFLP technique and direct seqencing The MSTN (exon 1) polymorphisms were investigated in all breeds, MSTN-Dra I/RFLP revealed three genotypes AA and BB were homozygous and AB was heterozygous. The calculated genotype frequencies were 0.270, 0.368 and 0.362 for AA, BB and AB genotype respectively. The allelic frequency was 0.451 for the A allele and 0.549 for the B allele. The average of the observed heterozygosity was 0.362 and the observed homozygosity was 0.638. The sequence data of MSTN gene of Native and Shami goats revealed 31 SNPs in nonfunctional region. In addition, in exon region there was 1 SNPs in both breed samples which did not change amino acid sequence and its silence mutation. In conclusion, the result of PCR-RFLP and SNP experiments obtained in this investigation were evaluated as very useful in genotype analysis of local goat breeds/populations. Thus, DNA polymorphisms in the Myostatin gene could be used as reliable genetic marker in breeding programs in this region.

A microscopic traffic flow model is developed that incorporates vehicle vibrations due to pavement condition. The Intelligent Driver (ID) model employs a fixed exponent so traffic behavior is the same regardless of the road condition. Thus, it ignores the underlying physics. To address this limitation, the proposed model employs the Pavement Condition Index (PCI) in describing traffic behavior. The performance of both models is evaluated on a 3000 m circular road using the Euler numerical discretization technique. The results show that the performance of the proposed model varies with the pavement condition (PCI), as expected. Furthermore, the traffic flow increases with vehicle speed. The oscillations in speed and density with the proposed model decrease as the PCI increases, and are larger when the speed is higher. Consequently, the results with the proposed model align more closely with reality as they are based on the PCI, and so are a more accurate representation of traffic behavior.

Abstract Purpose Yoghurt is a widely consumed dairy product around the world. It has healing properties and characteristics that are important for human health. Our goal was to see how using ewes' milk fed Spirulina platensis (SP) or fish oil (FO)-supplemented diets affected the chemical, physical, and nutritional properties of yoghurt, as well as the activity and survival of starter and probiotic bacteria during storage. Methods The collected milk from each ewe group was preheated to 65 °C and homogenized in a laboratory homogenizer, then heated to 90 °C for 5 min, cooled to 42 °C, and divided into two equal portions. The first portion was inoculated with 2.0% mixed starter culture (Lactobacillus bulgaricus and Streptococcus thermophilus, 1:1), whereas the second was inoculated with 2% mixed starter culture and 1% Bifidobacterium longum as a probiotic bacteria. Results SP yoghurt had the highest levels of short chain-FA, medium chain-FA, mostly C10:0, and long chain-FA, namely C16:0, C18:2 and the lowest levels of C18:0 and C18:1, followed by FO yoghurt. The addition of SP or FO to ewes' diets resulted in yoghurt with higher viable counts of L. bulgaricus and S. thermophilus, which were still >107 cfu/g at the end of storage, as well as a higher level of acetaldehyde content (P