Search

Background: Silver nanoparticles (AgNPs) are toxic to microorganisms and can potentially kill multidrug-resistant bacteria. Nanoparticles can be synthesized in many ways, such as physical or chemical methods. Recently, it has been found that plant molecules can perform the same reduction reactions necessary for the production of nanoparticles but in a much more efficient way. Results: Here, green chemistry was employed to synthesize AgNPs using leaf extracts of Cymbopogon citratus. The effects of different parameters such as temperature, pH, and the volume of plant extract were also tested using their absorbance pattern at different wavelengths. The Surface Plasmon Resonance (SPR) changed with the changes in parameters. Changes in temperature from 20 °C to 60 °C have changed the highest absorbance from 0.972 to 3.893 with an SPR of 470 nm. At higher pH (11.1), the particles become highly unstable and have irregular shapes and sizes. The peak shifts to the right at a lower pH level (3.97), indicating a smaller but unstable compound. We have also investigated the effect of the volume of plant extracts on the reaction time. The sample with the highest amount of plant extract showed the most absorbance with a value of 0.963 at λmax, calculated to be 470 nm. The total formation of the AgNPs was observed visually with a color change from yellow to brownish-black. UV-visible spectroscopy was used to monitor the quantitative formation of AgNPs, showing a signature peak in absorbance between 400 and 500 nm. We have estimated the size of the nanoparticles as 47 nm by comparing the experimental data with the theoretical value using Mieplot. The biosynthesized AgNPs showed enhanced antibacterial activity against several multidrug-resistant bacteria, determined based on the minimal inhibitory concentration and zone of inhibition. Conclusion: The findings of this study indicate that an aqueous extract of C. citratus can synthesize AgNPs when silver nitrate is used as a precursor, and AgNPs act as antimicrobial property enhancers, which can be used to treat antibiotic-resistant bacteria. Hence, mass production and green synthesis of AgNPs from C. citratus will be able to increase the overall health of the general population. Moreover, it will enormously reduce the costs for drug development and provide employment options in the remotely located source areas. Finally, our findings will influence further studies in this field to better understand the properties and applications of AgNPs and ultimately contribute to improving planetary health by increasing immunity with high biocompatibility and less drug toxicity. [ABSTRACT FROM AUTHOR]

Background/objectives: Insomnia is a frequent and distressing symptom with limited treatment in patients with cancer. Among the available treatments for insomnia, psychological interventions are some of the most assessed. While studies and reviews show promise of interventions improving insomnia in patients with cancer, inconsistent approaches to operationalizing and measuring insomnia combined with the heterogeneity of available treatments render comparisons and synthetization difficult. This review sought to rigorously synthesize psychological interventions for patients with cancer and insomnia by describing current therapies, identifying gaps in the literature, and offering supportive interventions., Methods: A comprehensive search of five databases-Ovid MEDLINE, Ovid Embase, Ovid PsycInfo, EBSCO CINAHL Plus with Full Text, and Cochrane Library-was conducted through 1 August 2024. The review included randomized trials and non-inferiority trials evaluating psychological interventions for patients with various types of cancers. Twenty-one studies were included, and study quality ranged from good to excellent, according to the PEDro scale., Results: The current evidence supports the use of cognitive behavioral therapy (CBT) to treat insomnia over and above psychoeducation alone, mindfulness-based stress reduction, Brief Behavioral Therapy, the Benson Relaxation Technique, progressive muscle relaxation, mindfulness meditation, mind-body bridging, and home-based psychological nursing. Digital, minimal, and internet-based intervention modalities are effective, though professional-delivered CBT proved most effective., Conclusions: CBT remains the most effective psychological intervention for insomnia in this population. Challenges exist regarding the implementation of CBT, so further research is warranted to identify the best psychological interventions for specific settings and subsets of patients with cancer.

The Internet of Things (IoT) is a significant technological advancement that allows for seamless device integration and data flow. The development of the IoT has led to the emergence of several solutions in various sectors. However, rapid popularization also has its challenges, and one of the most serious challenges is the security of the IoT. Security is a major concern, particularly routing attacks in the core network, which may cause severe damage due to information loss. Routing Protocol for Low-Power and Lossy Networks (RPL), a routing protocol used for IoT devices, is faced with selective forwarding attacks. In this paper, we present a federated learning-based detection technique for detecting selective forwarding attacks, termed FL-DSFA. A lightweight model involving the IoT Routing Attack Dataset (IRAD), which comprises Hello Flood (HF), Decreased Rank (DR), and Version Number (VN), is used in this technique to increase the detection efficiency. The attacks on IoT threaten the security of the IoT system since they mainly focus on essential elements of RPL. The components include control messages, routing topologies, repair procedures, and resources within sensor networks. Binary classification approaches have been used to assess the training efficiency of the proposed model. The training step includes the implementation of machine learning algorithms, including logistic regression (LR), K-nearest neighbors (KNN), support vector machine (SVM), and naive Bayes (NB). The comparative analysis illustrates that this study, with SVM and KNN classifiers, exhibits the highest accuracy during training and achieves the most efficient runtime performance. The proposed system demonstrates exceptional performance, achieving a prediction precision of 97.50%, an accuracy of 95%, a recall rate of 98.33%, and an F1 score of 97.01%. It outperforms the current leading research in this field, with its classification results, scalability, and enhanced privacy.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, marked by cognitive impairment. Currently, the available treatment provides only symptomatic relief and there is a great need to design and formulate new drugs to stabilize AD. In the search for a new anti-Alzheimer's drug, 3,5- bis (2-hydroxyethyl)-1,3,5-thiadiazinane-2-thione (THTT), a tetrahydro-2H-1,3,5-thiadiazine-2-thione derivative, was investigated against a scopolamine-induced Alzheimer's model. The selected test compound was administered intraperitoneally in three doses (15 mg/kg, 30 mg/kg, and 45 mg/kg). The test compound exhibited an IC50 value of 69.41 µg/mL, indicating its ability to inhibit the acetylcholinesterase enzyme. An antioxidant DPPH assay revealed that the IC50 value of the test compound was 97.75 µg/mL, which shows that the test compound possesses antioxidant activity. The results of behavior tests including the Y-maze and elevated plus maze (EPM) show that the test compound improved short-term memory and spatial memory, respectively. Furthermore, in the Morris water maze (MWM) and light/dark model, the test compound shows improvements in learning and memory. Moreover, the results of histological studies show that the test compound can protect the brain against the harmful effects of scopolamine. Overall, the findings of our investigation suggest that our chosen test compound has disease-modifying and neuroprotective activities against the scopolamine-induced Alzheimer's model. The test compound may be beneficial, subject to further elaborate investigation for anti-amyloid disease-modifying properties in AD.

Adenoid cystic carcinoma (ACC) of head and neck origin is associated with slow but relentless progression and systemic metastasis, resulting in poor long-term survival rates. ACC does not respond to conventional chemotherapy. Determination of molecular drivers may provide a rational basis for personalized therapy. Herein, we investigate the clinical and detailed molecular genomic features of a cohort of patients treated in Ireland and correlate the site of origin, molecular features, and outcomes. Clinical and genomic landscapes of all patients diagnosed with ACC over a twenty-year period (2002-2022) in a single unit in Ireland were examined and analyzed using fluorescence in situ hybridization, DNA sequencing, and bioinformatic analysis. Fourteen patients were included for analysis. Eleven patients had primary salivary gland ACC and three primary lacrimal gland ACC; 76.9% of the analyzed tumors displayed evidence of NFIB - MYB rearrangement at the 6q23.3 locus; 35% had mutations in NOTCH pathway genes; 7% of patients had a NOTCH1 mutation, 14.3% NOTCH2 mutation, and 14.3% NOTCH3 mutation. The presence of epigenetic modifications in ACC patients significantly correlated with worse overall survival. Our study identifies genetic mutations and signaling pathways that drive ACC pathogenesis, representing potential molecular and therapeutic targets.

This study investigates whether Andrographolide-loaded Lactose β-Cyclodextrin (ALN-βCD) nanoparticles enhance cognitive function, particularly spatial learning and memory. The successful conjugation of lactose to β-cyclodextrin was confirmed via 1H NMR spectroscopy, facilitating neuronal cell entry. The solvent evaporation method was used to create the nanoparticles, which were characterised for particle size, PDI, zeta potential, and drug release. The nanoparticles exhibited a size of 247.9 ± 3.2 nm, a PDI of 0.5 ± 0.02, and a zeta potential of 26.8 ± 2.5 mV. FTIR and TEM analyses, along with in vitro drug release and BBB permeability studies, confirmed their stability and efficacy. Behavioural tests, including the Elevated Plus Maze, Y-Maze, Object Recognition, and Locomotor Activity tests, demonstrated significant improvements in memory, motor coordination, and exploration time in the nanoparticle-treated groups. The group treated with ALN-βCD at a dose of 100 mg/kg/p.o. showed superior cognitive performance compared to the group receiving free andrographolides (AG). Biochemical assays indicated a significant reduction in acetylcholinesterase activity and lipid peroxidation, suggesting increased acetylcholine levels and reduced oxidative stress. Histopathological examination showed improved neuronal function without toxicity. The results showed significant improvements ( p < 0.001) in memory and cognitive abilities in experimental animals, highlighting the potential of ALN-βCD nanoparticles as a non-invasive treatment for memory loss. These promising findings warrant further exploration through clinical trials.

The treatment adherence of narcotics-addicted individuals with reduced incidences of relapse can be enhanced by a sustained drug release formulation of antinarcotics. So far, different drug formulations have been reported with sustained drug release periods of 28 and 35 days. To further enhance this duration, different formulations of injectable hydrogels (IHs) have been developed by combining low molecular weight (LMW) and high molecular weight (HMW) chitosan (CS) with guar gum (GG) and crosslinking them by sodium bi phosphate dibasic. The structural, morphological, and physicochemical properties of LMW-CS IH, and HMW-CS IH were evaluated using Fourier transform infrared spectroscopy (FT-IR), thermo-gravimetric analysis (TGA), scanning electron microscopy (SEM), and rheological, swelling, and biodegradation analysis. The HMW-CS IH showed high crosslinking, increased thermal stability, high mechanical strength, elevated swelling, and low biodegradation. The antinarcotic drugs naltrexone (NTX) and disulfiram (DSF) were loaded separately into the HMW-CS IH and LMW-CS IH. The release of NTX and DSF was investigated in phosphate buffer saline (PBS) and ethanol (0.3%, 0.4%, and 0.5%) over a 56-day period using an UV spectrophotometer. The drug release data were tested in zero-order, first-order, and Korsemeyer-Peppas mathematical models. In PBS, all prepared formulations followed non-Fickian drug release, while in ethanol, only NTX HMW-CS IH followed non-Fickian release in all three different concentrations of ethanol.

Conifers are an ecologically and economically important seed plant group that can provide significant insights into the evolution of land plants. Molecular phylogenetics has developed as an important approach in evolutionary studies, although there have been relatively few studies of conifers that employ large-scale data sourced from multiple nuclear genes. Target enrichment sequencing (target capture, exon capture, or Hyb-Seq) has developed as a key approach in modern phylogenomic studies. However, until now, there has been no bait set that specifically targets the entire conifer clade. REMcon is a target sequence capture probe set intended for family- and species-level phylogenetic studies of conifers that target c. 100 single-copy nuclear loci. We tested the REMcon probe set using 69 species, including 44 conifer genera across six families and four other gymnosperm taxa, to evaluate the efficiency of target capture to efficiently generate comparable DNA sequence data across conifers. The recovery of target loci was high, with, on average, 94% of the targeted regions recovered across samples with high read coverage. A phylogenetic analysis of these data produced a well-supported topology that is consistent with the current understanding of relationships among conifers. The REMcon bait set will be useful in generating relatively large-scale nuclear data sets consistently for any conifer lineage.

This paper presents geometric analyses of welded frames after free relaxing and vibratory stress relief (VSR). The tested frames were components of a prototype packaging machine. Two types of relaxation were carried out to remove stresses introduced as a result of the welding process. One of the frames was subjected to free relaxation, while the other one was subjected to accelerated vibration relaxation. Detection of the frame geometry changes was performed using a photogrammetric system. In addition, an evaluation of the geometry change was conducted for fifteen variants of a steel frame support. A comparative analysis of the geometric deviations of the frames after free and vibratory stress relief confirmed the assumption that the frame post vibration stress relief better reproduces the nominal dimensions. Nevertheless, it should be emphasized that after vibratory stress relief, the frame is not subject to further deformation, which is a desirable effect. In the case of free relaxing, the frame undergoes dimensional changes in a random manner. In summary, carrying out accelerated vibratory stress relief allows for control of spontaneous dimensional changes in the designed frame of a packaging machine resulting from spontaneous relaxation of stresses arising from the welding process. The shortening of the relaxation process of the welded frame is also an unquestionable advantage.

P53 overexpression plays a critical role in cancer pathogenesis by disrupting the intricate regulation of cellular proliferation. Despite its firmly established function as a tumor suppressor, elevated p53 levels can paradoxically contribute to tumorigenesis, influenced by factors such as exposure to carcinogens, genetic mutations, and viral infections. This phenomenon is observed across a spectrum of cancer types, including bladder (BLCA), ovarian (OV), cervical (CESC), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), diffuse large B-cell lymphoma (DLBC), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and uterine corpus endometrial carcinoma (UCEC). This broad spectrum of cancers is often associated with increased aggressiveness and recurrence risk. Effective therapeutic strategies targeting tumors with p53 overexpression require a comprehensive approach, integrating targeted interventions aimed at the p53 gene with conventional modalities such as chemotherapy, radiation therapy, and targeted drugs. In this extensive study, we present a detailed analysis shedding light on the multifaceted role of TP53 across various cancers, with a specific emphasis on its impact on disease-free survival (DFS). Leveraging data from the TCGA database and the GTEx dataset, along with GEPIA, UALCAN, and STRING, we identify TP53 overexpression as a significant prognostic indicator, notably pronounced in prostate adenocarcinoma (PRAD). Supported by compelling statistical significance ( p < 0.05), our analysis reveals the distinct influence of TP53 overexpression on DFS outcomes in PRAD. Additionally, graphical representations of overall survival (OS) underscore the notable disparity in OS duration between tumors exhibiting elevated TP53 expression (depicted by the red line) and those with lower TP53 levels (indicated by the blue line). The hazard ratio (HR) further emphasizes the profound impact of TP53 on overall survival. Moreover, our investigation delves into the intricate TP53 protein network, unveiling genes exhibiting robust positive correlations with TP53 expression across 13 out of 27 cancers. Remarkably, negative correlations emerge with pivotal tumor suppressor genes. This network analysis elucidates critical proteins, including SIRT1, CBP, p300, ATM, DAXX, HSP 90-alpha, Mdm2, RPA70, 14-3-3 protein sigma, p53, and ASPP2, pivotal in regulating cell cycle dynamics, DNA damage response, and transcriptional regulation. Our study underscores the paramount importance of deciphering TP53 dynamics in cancer, providing invaluable insights into tumor behavior, disease-free survival, and potential therapeutic avenues.

A promising method for additive manufacturing that makes it possible to produce intricate and personalized parts is selective laser melting (SLM). However, the mechanical properties of as-corroded SLM parts are still areas of concern. This research investigates the mechanical behavior of SLM parts that are exposed to a saline environment containing a 3.5% NaCl solution for varying lengths of time. The exposure times chosen for this study were 10 days, 20 days, and 30 days. The results reveal that the tensile strength of the parts is significantly affected by the duration of exposure. Additionally, the study also examined the influence of porosity on the corrosion behavior of the parts. The analysis included studying the mass loss of the parts over time, and a regression analysis was conducted to analyze the relationship between exposure time and mass loss. In addition, the utilization of scanning electron microscopy (SEM) and X-ray photo spectroscopy (XPS) techniques yielded valuable insights into the fundamental mechanisms accountable for the observed corrosion and mechanical behavior. It was found that the presence of corrosion products (i.e., oxide layer) and pitting contributed to the degradation of the SLM parts in the saline environment. This research emphasizes the importance of considering part thickness in the design of SLM components for corrosive environments and provides insights for enhancing their performance and durability.

In the quest for advanced materials with diverse applications in optoelectronics and energy storage, we delve into the fascinating world of halide perovskites, focusing on SiAuF 3 and SiCuF 3 . Employing density functional theory (DFT) as our guiding light, we conduct a comprehensive comparative study of these two compounds, unearthing their unique structural, electronic, elastic, and optical attributes. Structurally, SiAuF 3 and SiCuF 3 reveal their cubic nature, with SiCuF 3 demonstrating superior stability and a higher bulk modulus. Electronic investigations shed light on their metallic behavior, with Fermi energy levels marking the boundary between valence and conduction bands. The band structures and density of states provide deeper insights into the contributions of electronic states in both compounds. Elastic properties unveil the mechanical stability of these materials, with SiCuF 3 exhibiting increased anisotropy compared to SiAuF 3 . Our analysis of optical properties unravels distinct characteristics. SiCuF 3 boasts a higher refractive index at lower energies, indicating enhanced transparency in specific ranges, while SiAuF 3 exhibits heightened reflectivity in select energy intervals. Further, both compounds exhibit remarkable absorption coefficients, showcasing their ability to absorb light at defined energy thresholds. The energy loss function (ELF) analysis uncovers differential absorption behavior, with SiAuF 3 absorbing maximum energy at 6.9 eV and SiCuF 3 at 7.2 eV. Our study not only enriches the fundamental understanding of SiAuF 3 and SiCuF 3 but also illuminates their potential in optoelectronic applications. These findings open doors to innovative technologies harnessing the distinctive qualities of these halide perovskite materials. As researchers seek materials that push the boundaries of optoelectronics and energy storage, SiAuF 3 and SiCuF 3 stand out as promising candidates, ready to shape the future of these fields.

The study delves into the multifaceted potential of quercetin (Qu), a phytoconstituent found in various fruits, vegetables, and medicinal plants, in combination with silver nanoparticles (AgNPs). The research explores the synthesis and characterization of AgNPs loaded with Qu and investigates their pharmaceutical applications, particularly focusing on antibacterial properties. The study meticulously evaluates Qu's identity, and physicochemical properties, reaffirming its suitability for pharmaceutical use. The development of Qu-loaded AgNPs demonstrates their high drug entrapment efficiency, ideal particle characteristics, and controlled drug release kinetics, suggesting enhanced therapeutic efficacy and reduced side effects. Furthermore, the research examines the antibacterial activity of Qu in different solvents, revealing distinct outcomes. Qu, both in methanol and water formulations, exhibits antibacterial activity against Escherichia coli , with the methanol formulation displaying a slightly stronger efficacy. In conclusion, this study successfully synthesizes AgNPs loaded with Qu and highlights their potential as a potent antibacterial formulation. The findings underscore the influence of solvent choice on Qu's antibacterial properties and pave the way for further research and development in drug delivery systems and antimicrobial agents. This innovative approach holds promise for addressing microbial resistance and advancing pharmaceutical formulations for improved therapeutic outcomes.

Solid lipid nanoparticles (SLNs) have the advantages of a cell-specific delivery and sustained release of hydrophobic drugs that can be exploited against infectious diseases. The topical delivery of hydrophobic drugs needs pharmaceutical strategies to enhance drug permeation, which is a challenge faced by conventional formulations containing a drug suspended in gel, creams or ointments. We report the fabrication and optimization of SLNs with sulconazole (SCZ) as a model hydrophobic drug and then a formulation of an SLN-based topical gel against fungal infections. The SLNs were optimized through excipients of glyceryl monostearate and Phospholipon ® 90 H as lipids and tween 20 as a surfactant for its size, drug entrapment and sustained release and resistance against aggregation. The SCZ-SLNs were physically characterized for their particle size (89.81 ± 2.64), polydispersity index (0.311 ± 0.07), zeta potential (-26.98 ± 1.19) and encapsulation efficiency (86.52 ± 0.53). The SCZ-SLNs showed sustained release of 85.29% drug at the 12 h timepoint. The TEM results demonstrated spherical morphology, while DSC, XRD and FTIR showed the compatibility of the drug inside SLNs. SCZ-SLNs were incorporated into a gel using carbopol and were further optimized for their rheological behavior, pH, homogeneity and spreadability on the skin. The antifungal activity against Candida albicans and Trichophyton rubrum was increased in comparison to a SCZ carbopol-based gel. In vivo antifungal activity in rabbits presented faster healing of skin fungal infections. The histopathological examination of the treated skin from rabbits presented restoration of the dermal architecture. In summary, the approach of formulating SLNs into a topical gel presented an advantageous drug delivery system against mycosis.

Several leaks appeared in a mild steel (MS) pipe jet nozzle installed in a direct impact test rig after a few months of operation in erosive flow at the Centre for Erosion-Corrosion Research. The locations of perforation leaks were primarily upstream, but severe wall thinning was also noticed adjacent to the exit section. In this paper, a failure analysis was carried out on the leaking of a pipe jet nozzle, and the results are discussed in detail. The investigation carried out includes visual observation, scanning electron microscopy, 3D scanning, energy-dispersive spectroscopy, and laser profilometry measurements. In addition, numerical simulations based on computational fluid dynamics (CFD) and the discrete phase model (DPM) were conducted to investigate the root cause of the failure of leaks in the pipe jet nozzle. Further CFD-DPM simulations were performed on three different pipe jet designs for liquid-solid flow conditions, and were compared to find an alternative design to prevent the failure of the pipe jet nozzles. It was found that the increase in turbulence along with multiple impacts of particles on the wall generate leaks and cracks in the pipe jet nozzle. Moreover, the CFD-DPM showed a five-fold reduction in the maximum erosion rate; this was observed in the replacement of failed pipes with the proposed alternative nozzle pipe design featuring a chamfer reducer section. The CFD-DPM analysis of all geometric configurations showed that alteration of reducer section design has the greatest impact on erosive wear mitigation.

Aphids are a serious threat to rapeseed ( Brassica napus L.) production, and cause unmanageable loss. Therefore, effective prevention and management strategies are urgently required to avoid losses. Bacillus amyloliquefaciens AK-12 isolated from a dead aphid with aphicidal activity was tagged with a green fluorescent protein through a natural transformation. The transformed strains were checked for stability and growth, and the best-performing strain was tested for its colonization inside and outside the rapeseed plant. The stability of AK-12-GFP reached more than 95%, and the growth curve was consistent with that of AK-12. After 30 days of treatment, the colonization of 1 × 10 6 CFU/g was recorded in rapeseed leaves. Interestingly, AK-12 reduced the aphid transmission rate compared with the control and improved the growth of the rapeseed seedlings. Meanwhile, the AK-12 strain also exhibited phosphorus, potassium-solubilizing, and nitrogen-fixing activity, and produced 2.61 µg/mL of IAA at 24 h. Regulation in the activity of four enzymes was detected after the AK-12 treatment. Phenylalanine ammonia lyase (PAL) was recorded at a maximum of 86.84 U/g after 36 h, and catalase (CAT) decreased after 48 h; however, peroxidase (POD) and polyphenol oxidase (PPO) reached the maximum within 12 h of AK-12 application. Additionally, important resistance genes related to these enzymes were upregulated, indicating the activation of a defense response in the rapeseed against aphids. In conclusion, defense enzymes and defense-related gene activation could improve the pest resistance in rapeseed, which has good application prospects for the future to be developed into biopesticide.

Sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is an inborn error of metabolism caused by inactivating mutations in SGPL1 , the gene encoding sphingosine-1-phosphate lyase (SPL), an essential enzyme needed to degrade sphingolipids. SPLIS features include glomerulosclerosis, adrenal insufficiency, neurological defects, ichthyosis, and immune deficiency. Currently, there is no cure for SPLIS, and severely affected patients often die in the first years of life. We reported that adeno-associated virus (AAV) 9-mediated SGPL1 gene therapy (AAV-SPL) given to newborn Sgpl1 knockout mice that model SPLIS and die in the first few weeks of life prolonged their survival to 4.5 months and prevented or delayed the onset of SPLIS phenotypes. In this study, we tested the efficacy of a modified AAV-SPL, which we call AAV-SPL 2.0, in which the original cytomegalovirus (CMV) promoter driving the transgene is replaced with the synthetic "CAG" promoter used in several clinically approved gene therapy agents. AAV-SPL 2.0 infection of human embryonic kidney (HEK) cells led to 30% higher SPL expression and enzyme activity compared to AAV-SPL. Newborn Sgpl1 knockout mice receiving AAV-SPL 2.0 survived ≥ 5 months and showed normal neurodevelopment, 85% of normal weight gain over the first four months, and delayed onset of proteinuria. Over time, treated mice developed nephrosis and glomerulosclerosis, which likely resulted in their demise. Our overall findings show that AAV-SPL 2.0 performs equal to or better than AAV-SPL. However, improved kidney targeting may be necessary to achieve maximally optimized gene therapy as a potentially lifesaving SPLIS treatment.

Background: Health-related quality of life is rapidly becoming recognized as an important indicator of how a disease affects patient lives and for evaluating the quality of care, especially for chronic conditions such as chronic kidney disease (CKD). Objectives: This study is an attempt to assess the quality of life in patients with chronic kidney disease at MMIMSR and also identify characteristics that may be associated with their worsening quality of life. Materials and Methods: This cross-sectional investigation was conducted at the in-patient department (IPD) of the MMIMSR hospital. This study included 105 CKD patients and used a systematic random sampling method for quantitative analysis. This study utilized a 36-item short-form SF-36 (v1.3) questionnaire to assess HRQoL in CKD patients. Descriptive statistics were employed at the baseline. Chi square and ANOVA were used to draw comparisons between two groups or more than two groups, respectively. Logistic regression analysis was utilized to identify the potential QoL determinants. A p value of 0.05 or lower was used to determine statistical significance. Results: Among a total of 105 participants, the mean (±standard deviation) age was found to be 54.53 ± 13.47 years; 48 were male patients, and 57 were female patients. Diabetes Mellitus (61.9%), hypertension (56.2%), chronic glomerulonephritis (7.6%), chronic pyelonephritis (6.7%), and polycystic kidney disease (5.7%) were identified to be the most frequent disorders associated with CKD. The current study also demonstrated that the HRQoL score domains such as symptom problem list, the effect of kidney disease, and the burden of kidney disease decline significantly and progressively as the patient advances into higher stages of CKD ( p = 0.005). A similar pattern was observed in work status, sleep, and general health ( p < 0.005). Additionally, a statistically significant difference was noted for cognitive function, quality of social interaction, overall health, dialysis staff encouragement, patient satisfaction, social support, physical functioning, role of physical health, pain, emotional well-being, role of emotional health, social functioning, and energy fatigue ( p < 0.005). The mean difference for PCS and MCS based on CKD stages was found to be statistically significant ( p < 0.005). The PCS and MCS showed a positive correlation with GFR (r = 0.521), and Hb (r = 0.378), GFR (r = 0.836), and Hb (r = 0.488), respectively. Conclusions: The findings of this study demonstrated that a significant decrease in HRQoL was observed among CKD patients, with a progressive deterioration of HRQoL dimensions as the patient advances to end-stage renal disease. This study also revealed that CKD imposes various restrictions on patients' day-to-day lives, particularly in terms of their physical and mental functioning, even in the initial stages of the disease.

Cardiac disorders are a leading cause of global casualties, emphasizing the need for the initial diagnosis and prevention of cardiovascular diseases (CVDs). Electrocardiogram (ECG) procedures are highly recommended as they provide crucial cardiology information. Telemedicine offers an opportunity to provide low-cost tools and widespread availability for CVD management. In this research, we proposed an IoT-based monitoring and detection system for cardiac patients, employing a two-stage approach. In the initial stage, we used a routing protocol that combines routing by energy and link quality (REL) with dynamic source routing (DSR) to efficiently collect data on an IoT healthcare platform. The second stage involves the classification of ECG images using hybrid-based deep features. Our classification system utilizes the "ECG Images dataset of Cardiac Patients", comprising 12-lead ECG images with four distinct categories: abnormal heartbeat, myocardial infarction (MI), previous history of MI, and normal ECG. For feature extraction, we employed a lightweight CNN, which automatically extracts relevant ECG features. These features were further optimized through an attention module, which is the method's main focus. The model achieved a remarkable accuracy of 98.39%. Our findings suggest that this system can effectively aid in the identification of cardiac disorders. The proposed approach combines IoT, deep learning, and efficient routing protocols, showcasing its potential for improving CVD diagnosis and management.

Inflammasomes have recently been implicated in the pathogenesis of several chronic inflammatory disorders, such as diabetes and obesity. The aim of this meta-analysis was to investigate the possible role of the NLRP3 inflammasome in obesity and polycystic ovarian syndrome (PCOS). A comprehensive search of electronic databases was conducted to identify studies investigating NLRP3 its related components (Caspase 1, ASC and IL-1β) in adipose tissue and/or blood from obese individuals compared to non-obese controls. Another search was conducted for studies investigating NLRP3 in PCOS women and animal models. The ssearched databases included Medline, EMBASE, Cochrane Library, PubMed, Clinicaltrials.gov, the EU Clinical Trials Register and the WHO International Clinical Trials Register. The quality and risk of bias for the included articles were assessed using the modified Newcastle-Ottawa scale. Data were extracted and pooled using RevMan software for the calculation of the standardized mean difference (SMD) and 95% confidence interval (CI). Twelve eligible studies were included in the obesity systematic review and nine in the PCOS review. Of the obesity studies, nine ( n = 270) were included in the meta-analysis, which showed a significantly higher adipose tissue NLRP3 gene expression in obese ( n = 186) versus non-obese ( n = 84) participants (SMD 1.07; 95% CI, 0.27, 1.87). Pooled analysis of adipose tissue IL-1β data from four studies showed significantly higher IL-1β gene expression levels in adipose tissue from 88 obese participants versus 39 non-obese controls (SMD 0.56; 95% CI, 0.13, 0.99). Meta-analysis of adipose tissue ASC data from four studies showed a significantly higher level in obese ( n = 109) versus non-obese ( n = 42) individuals (SMD 0.91, 95% CI, 0.30, 1.52). Of the nine PCOS articles, three were human ( n = 185) and six were animal studies utilizing PCOS rat/mouse models. All studies apart from one article consistently showed upregulated NLRP3 and its components in PCOS women and animal models. In conclusion, obesity and PCOS seem to be associated with upregulated expression of NLRP3 inflammasome components. Further research is required to validate these findings and to elucidate the role of NLRP3 in obesity and PCOS.

This research is being conducted to learn more about various compounds and their potential uses in various fields such as renewable energy, electrical conductivity, the study of optoelectronic properties, the use of light-absorbing materials in photovoltaic device thin-film LEDs, and field effect transistors (FETs). AgZF3 (Z = Sb, Bi) compounds, which are simple, cubic, ternary fluoro-perovskites, are studied using the FP-LAPW and low orbital algorithm, both of which are based on DFT. Structure, elasticity and electrical and optical properties are only some of the many features that can be predicted. The TB-mBJ method is used to analyze several property types. An important finding of this study is an increase in the bulk modulus value after switching Sb to Bi as the metallic cation designated as "Z" demonstrates the stiffness characteristic of a material. The anisotropy and mechanical balance of the underexplored compounds are also revealed. Our compounds are ductile, as evidenced by the calculated Poisson ratio, Cauchy pressure, and Pugh ratio values. Both compounds exhibit indirect band gaps (X-M), with the lowest points of the conduction bands located at the evenness point X and the highest points of the valence bands located at the symmetry point M. The principal peaks in the optical spectrum can be understood in light of the observed electronic structure.

This work describes an ab initio principle computational examination of the optical, structural, elastic, electronic and mechanical characteristics of aluminum-based compounds AlRF 3 (R = N, P) halide-perovskites. For optimization purposes, we used the Birch-Murnaghan equation of state and discovered that the compounds AlNF 3 and AlPF 3 are both structurally stable. The IRelast software was used to compute elastic constants (ECs) of the elastic properties. The aforementioned compounds are stable mechanically. They exhibit strong resistance to plastic strain, possess ductile nature and anisotropic behavior and are scratch-resistant. The modified Becke-Johnson (Tb-mBJ) approximation was adopted to compute various physical properties, revealing that AlNF 3 and AlPF 3 are both metals in nature. From the density of states, the support of various electronic states in the band structures are explained. Other various optical characteristics have been calculated from the investigations of the band gap energy of the aforementioned compounds. These compounds absorb a significant amount of energy at high levels. At low energy levels, the compound AlNF 3 is transparent to incoming photons, whereas the compound AlPF 3 is somewhat opaque. The examination of the visual details led us to the deduction that the compounds AlNF 3 and AlPF 3 may be used in making ultraviolet devices based on high frequency. This computational effort is being made for the first time in order to investigate the aforementioned properties of these chemicals, which have yet to be confirmed experimentally.

Herein, a novel optical chemosensor, ( CM1 = 2, 6-di((E)-benzylidene)-4-methylcyclohexan-1-one), was designed/synthesized and characterized by 1 H-NMR and FT-IR spectroscopy. The experimental observations indicated that CM1 is an efficient and selective chemosensor towards Cd 2+ , even in the presence of other metal ions, such as Mn 2+ , Cu 2+ , Co 2+, Ce 3+ , K + , Hg 2+ , , and Zn 2+ in the aqueous medium. The newly synthesized chemosensor, CM1 , showed a significant change in the fluorescence emission spectrum upon coordination with Cd 2+ . The formation of the Cd 2+ complex with CM1 was confirmed from the fluorometric response. The 1:2 combination of Cd 2+ with CM1 was found optimum for the desired optical properties, which was confirmed through fluorescent titration, Job's plot, and DFT calculation. Moreover, CM1 showed high sensitivity towards Cd 2+ with a very low detection limit (19.25 nM). Additionally, the CM1 was recovered and recycled by the addition of EDTA solution that combines with Cd 2+ ion and, hence, frees up the chemosensor.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for COVID-19, which was declared a global pandemic in March 2020 by the World Health Organization (WHO). Since SARS-CoV-2 main protease plays an essential role in the virus's life cycle, the design of small drug molecules with lower molecular weight has been a promising development targeting its inhibition. Herein, we evaluated the novel peptidomimetic azatripeptide and azatetrapeptide nitriles against SARS-CoV-2 main protease. We employed molecular dynamics (MD) simulations to elucidate the selected compounds' binding free energy profiles against SARS-CoV-2 and further unveil the residues responsible for the drug-binding properties. Compound 8 exhibited the highest binding free energy of -49.37 ± 0.15 kcal/mol, followed by compound 7 (-39.83 ± 0.19 kcal/mol), while compound 17 showed the lowest binding free energy (-23.54 ± 0.19 kcal/mol). In addition, the absorption, distribution, metabolism, and excretion (ADME) assessment was performed and revealed that only compound 17 met the drug-likeness parameters and exhibited high pharmacokinetics to inhibit CYP1A2, CYP2C19, and CYP2C9 with better absorption potential and blood-brain barrier permeability (BBB) index. The additional intermolecular evaluations suggested compound 8 as a promising drug candidate for inhibiting SARS-CoV-2 Mpro. The substitution of isopropane in compound 7 with an aromatic benzene ring in compound 8 significantly enhanced the drug's ability to bind better at the active site of the SARS-CoV-2 Mpro.

The rolling process of rebar steel production is one of the well established manufacturing processes; however, it should be subjected to revision and redesign for productivity enhancement and power reduction throughout the slit rolling process. In this work, slitting passes are extensively reviewed and modified for the attainment of better rolling stability and reduction in power consumption. The study has been applied for grade B400B-R Egyptian rebar steel, which is equivalent to steel grade ASTM A615M, Grade 40. Traditionally, the rolled strip in the rolling pass is edged before implementing a slitting pass using grooved rolls; this produces a single barreled strip. This single barrel form causes instability in the next slitting stand on the pressing by the slitting roll knife. Multiple industrial trials are attempted to achieve the deformation of the edging stand using a grooveless roll. As a result, a double barreled slab is produced. In parallel, finite element simulations of the edging pass are performed using grooved and grooveless rolls, and similar slab geometry with single and double barreled form are produced. In addition, further finite element simulations of the slitting stand are execute using idealized single barreled strips. The power calculated by the FE simulations of the single barreled strip is (245 kW), which is in acceptable agreement with the experimental observations in the industrial process (216 kW). This result validates the FE modeling parameters such as material model and boundary conditions. The FE modeling is extended to the slit rolling stand of a double barreled strip, which was previously produced by the grooveless edging rolls. It is found that the power consumption is (165 kW) 12% lower than the power consumed (185 kW) for slitting the single barreled strip.

We present an analysis of the pseudorapidity η and transverse momentum pT distributions of charged hadrons in pp collisions for the kinematic range of 01 GeV/c at 0.9 and 2.36 TeV within the experimental errors, while Dire overshoots and Vicia undershoots the data by 50% each. At 7 TeV, the Dire module presents a good prediction, whereas the Simple and Vincia modules underestimate the data within 30% and 50%. Comparing the Simple module of the Pythia model and the predictions of the CRMC models with the experimental data shows that at 0.9 TeV, EPOS-LHC has better results than the others. At 2.36 GeV, the cosmic rays Monte Carlo (CRMC) models have better prediction than the Simple module of Pythia at low pT, while QGSJETII-04 predicts well at high pT. QGSJETII-04 and EPOS-LHC have closer results than the Pythia-Simple and Sibyll2.3d at 7 TeV. In the case of the pseudorapidity distributions, only the Pythia-Simple reproduced the experimental measurements at all energies. The Dire module overestimates, while Vincia underestimates the data in decreasing order of discrepancy (20%, 12%, 5%) with energy. All CRMC models underestimate the data over the entire η range at all energies by 20%. The angular ordering of partons and the parton fragmentation could be possible reasons for this deviation. Furthermore, we used the two-component standard distribution to fit the pT spectra to the experimental data and extracted the effective temperature (Teff) and the multiplicity parameter (N0). It is observed that Teff increases with the increase in the center of mass energy. The fit yielded 0.20368±0.01, 0.22348±0.011, and 0.24128±0.012 GeV for 0.9, 2.36, and 7 TeV, respectively. This shows that the system at higher energies freezes out earlier than lower ones because they quickly attain the equilibrium state.

Liver fibrosis is a major pathological feature of chronic liver disease and effective therapies are limited at present. The present study focuses on the hepatoprotective potential of L . corymbulosum against carbon tetrachloride (CCl 4 )-induced liver damage in rats. Analysis of Linum corymbulosum methanol extract (LCM) using high-performance liquid chromatography (HPLC) revealed the presence of rutin, apigenin, catechin, caffeic acid and myricetin. CCl 4 administration lowered ( p < 0.01) the activities of antioxidant enzymes and reduced glutathione (GSH) content as well as soluble proteins, whereas the concentration of H 2 O 2 , nitrite and thiobarbituric acid reactive substances was higher in hepatic samples. In serum, the level of hepatic markers and total bilirubin was elevated followed by CCl 4 administration. The expression of glucose-regulated protein (GRP78), x-box binding protein-1 total (XBP-1 t), x-box binding protein-1 spliced (XBP-1 s), x-box binding protein-1 unspliced (XBP-1 u) and glutamate-cysteine ligase catalytic subunit (GCLC) was enhanced in CCl 4 -administered rats. Similarly, the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemo attractant protein-1 (MCP-1) was strongly increased with CCl 4 administration to rats. Co-administration of LCM along with CCl 4 to rats lowered ( p < 0.05) the expression of the above genes. Histopathology of the liver showed hepatocyte injury, leukocyte infiltration and damaged central lobules in CCl 4 -treated rats. However, LCM administration to CCl 4 -intoxicated rats restored the altered parameters towards the levels of control rats. These outcomes indicate the existence of antioxidant and anti-inflammatory constituents in the methanol extract of L. corymbulosum .

The aim of this work was to assess the limiting rate of eugenol (Eg) and eugenyl-glycidyl methacrylate (EgGMA) at which the ideal degree of conversion (DC) of resin composites is achieved. For this, two series of experimental composites, containing, besides reinforcing silica and a photo-initiator system, either EgGMA or Eg molecules at 0-6.8 wt% per resin matrix, principally consisting of urethane dimethacrylate (50 wt% per composite), were prepared and denoted as UGx and UEx, where x refers to the EgGMA or Eg wt% in the composite, respectively. Disc-shaped specimens (5 × 1 mm) were fabricated, photocured for 60 s, and analyzed for their Fourier transform infrared spectra before and after curing. The results revealed concentration-dependent DC, increased from 56.70% (control; UG0 = UE0) to 63.87% and 65.06% for UG3.4 and UE0.4, respectively, then dramatically decreased with the concentration increase. The insufficiency in DC due to EgGMA and Eg incorporation, i.e., DC below the suggested clinical limit (>55%), was observed beyond UG3.4 and UE0.8. The mechanism behind such inhibition is still not fully determined; however, radicals generated by Eg may drive its free radical polymerization inhibitory activity, while the steric hindrance and reactivity of EgGMA express its traced effect at high percentages. Therefore, while Eg is a severe inhibitor for radical polymerization, EgGMA is safer and can be used to benefit resin-based composites when used at a low percentage per resin.

This research investigates the machinability of Inconel 718 under conventional machining speeds using three different tool coatings in comparison with uncoated tool during milling operation. Cutting speed, feed rate and depth of cut were selected as variable machining parameters to analyze output responses including surface roughness, burr formation and tool wear. It was found that uncoated and AlTiN coated tools resulted in lower tool wear than nACo and TiSiN coated tools. On the other hand, TiSiN coated tools resulted in highest surface roughness and burr formation. Among the three machining parameters, feed was identified as the most influential parameter affecting burr formation. Grey relational analysis identified the most optimal experimental run with a speed of 14 m/min, feed of 1 μm/tooth, and depth of cut of 70 μm using an AlTiN coated tool. ANOVA of the regression model identified the tool coating parameter as most effective, with a contribution ratio of 41.64%, whereas cutting speed and depth of cut were found to have contribution ratios of 18.82% and 8.10%, respectively. Experimental run at response surface optimized conditions resulted in reduced surface roughness and tool wear by 18% and 20%, respectively.

Sphingosine kinase 1 (SPHK1) and the sphingosine-1-phosphate (S1P) signaling pathway have been shown to play a role in pulmonary arterial hypertension (PAH). S1P is an important stimulus for pulmonary artery smooth muscle cell (PASMC) proliferation and pulmonary vascular remodeling. We aimed to examine the specific roles of SPHK1 in PASMCs during pulmonary hypertension (PH) progression. We generated smooth muscle cell-specific, Sphk1 -deficient ( Sphk1 f/f TaglnCre + ) mice and isolated Sphk1 -deficient PASMCs from SPHK1 knockout mice. We demonstrated that Sphk1 f/f TaglnCre + mice are protected from hypoxia or hypoxia/Sugen-mediated PH, and pulmonary vascular remodeling and that Sphk1 -deficient PASMCs are less proliferative compared with ones isolated from wild-type (WT) siblings. S1P or hypoxia activated yes-associated protein 1 (YAP1) signaling by enhancing its translocation to the nucleus, which was dependent on SPHK1 enzymatic activity. Further, verteporfin, a pharmacologic YAP1 inhibitor, attenuated the S1P-mediated proliferation of hPASMCs, hypoxia-mediated PH, and pulmonary vascular remodeling in mice and hypoxia/Sugen-mediated severe PH in rats. Smooth muscle cell-specific SPHK1 plays an essential role in PH via YAP1 signaling, and YAP1 inhibition may have therapeutic potential in treating PH.

Introduction: The psychometric properties of the Arab translation of the Compulsive Internet Use Scale (CIUS) have been previously studied by confirmatory factor analysis (CFA) with AMOS software using the asymptotically distribution-free (ADF) estimator. Unidimensionality has been achieved at the cost of correlating several item variance errors. However, several reviews of SEM software packages and estimation methods indicate that the option of robust standard errors is not present in the AMOS package and that ADF estimation may yield biased parameter estimates. We therefore explored a second analysis through item response theory (IRT) using the parametric graded response model (GRM) and the marginal maximum likelihood (MML) estimation method embedded in the LTM package of R software. Differential item functioning (DIF) or item bias across subpopulations was also explored within IRT framework as different samples were investigated. The objective of the current study is to (1) analyze the Arab CIUS scale with IRT, (2) investigate DIF in three samples, and (3) contribute to the ongoing debate on Internet-use-related addictive behaviors using the CIUS items as a proxy., Methods: We assessed three samples of people, one in Algeria and two in Lebanon, with a total of 1520 participants., Results: Almost three out of every five items were highly related to the latent construct. However, the unidimensionality hypothesis was not supported. Furthermore, besides being locally dependent, the scale may be weakened by DIF across geographic regions. Some of the CIUS items related to increasing priority, impaired control, continued use despite harm, and functional impairment as well as withdrawal and coping showed good discriminative capabilities. Those items were endorsed more frequently than other CIUS items in people with higher levels of addictive Internet use., Conclusions: Contrary to earlier ADF estimation findings, unidimensionality of the CIUS scale was not supported by IRT parametric GRM in a large sample of Arab speaking participants. The results may be helpful for scale revision. By proxy, the study contributes to testing the validity of addiction criteria applied to Internet use related-addictive behaviors.

Background: Brain metastases (BMs) carry a high morbidity and mortality burden. Neoadjuvant stereotactic radiotherapy (NaSRT) has shown promising results. We systematically reviewed the literature on NaSRT for BMs., Methods: PubMed, EMBASE, Scopus, Web-of-Science, Cochrane, and ClinicalTrial.gov were searched following the PRISMA guidelines to include studies and ongoing trials reporting NaSRT for BMs. Indications, protocols, and outcomes were analyzed using indirect random-effect meta-analyses., Results: We included 7 studies comprising 460 patients with 483 BMs, and 13 ongoing trials. Most BMs originated from non-small lung cell carcinoma (41.4%), breast cancer (18.7%) and melanoma (43.6%). Most patients had single-BM (69.8%) located supratentorial (77.8%). Patients were eligible if they had histologically-proven primary tumors and ≤4 synchronous BMs candidate for non-urgent surgery and radiation. Patients with primary tumors clinically responsive to radiotherapy, prior brain radiation, and leptomeningeal metastases were deemed non-eligible. Median planning target volume was 9.9 cm 3 (range, 2.9-57.1), and NaSRT was delivered in 1-fraction (90.9%), 5-fraction (4.8%), or 3-fraction (4.3%), with a median biological effective dose of 39.6 Gy10 (range, 35.7-60). Most patients received piecemeal (76.3%) and gross-total (94%) resection after a median of 1-day (range, 1-10) post-NaSRT. Median follow-up was 19.2-months (range, 1-41.3). Actuarial post-treatment rates were 4% (95%CI: 2-6%) for symptomatic radiation necrosis, 15% (95%CI: 12-18%) and 47% (95%CI: 42-52%) for local and distant recurrences, 6% (95%CI: 3-8%) for leptomeningeal metastases, 81% (95%CI: 75-87%) and 59% (95%CI: 54-63%) for 1-year local tumor control and overall survival., Conclusion: NaSRT is effective and safe for BMs. Ongoing trials will provide high-level evidence on long-term post-treatment outcomes, further compared to adjuvant stereotactic radiotherapy.

Background : Children with Down Syndrome (C-DS) have language, cognitive and communication difficulties, in addition to consistent physical inactivity that contributes to poor health and higher-disability-adjusted life years. The purpose of this study was to determine the correlation between the use of electronic technology and levels of physical activity in C-DS in the Riyadh region of Saudi Arabia. Methods : A cross-sectional study was conducted with 49 mothers, where each had a child (6-12 years of age) with Down Syndrome (DS), and who were recruited using purposive sampling from three DS centers in Riyadh, Saudi Arabia. The Children's Physical Activity Questionnaire and Research Questionnaire on the Impact of Technology on Children were used. Descriptive statistics were used to describe the demographics. Pearson's correlation, Student's t -test and the Chi-square test were used to assess the association between technology use, physical activity levels and socio-demographic variables. Results : There was no significant correlation between physical activity and the use of technology by C-DS. However, there was a negative correlation between a high level of physical activity and technology use (R = -0.037). Although, no significant correlation between the mother's characteristics and technology use was found; there was a significantly positive correlation ( p = 0.05) between the education level of mothers and the technology use by C-DS. Nonetheless, there was no association between the physical activity level and the gender of the child with DS. Conclusions : This study found that no significant relationship exists between the use of electronic gadgets and the level of physical activity in C-DS.

Cerebral palsy is a common motor disorder that results in long-term impairment. The purpose of this study was to find out what factors influence Saudi mothers' compliance with their Children with Cerebral Palsy (C-CP ) Home Exercise Program (HEP). A self-administered online questionnaire was used to perform this qualitative research study on a group of 113 mothers who had children with CP. The study included mothers with children from birth to 12 years old who had received a HEP prescription from a physiotherapist. The measuring instrument tool was a questionnaire with two sections: demographic characteristics and a questionnaire about the parents' adherence to the HEP. The questionnaire utilized in this study was subjected to a reliability analysis, and the derived Cronbach's alpha was found to be 0.814 for the questionnaire (which had 17 phrases). These results imply that the questionnaire is reliable. A total of 113 responses were received, with 4 incomplete responses being eliminated. The majority of mothers (66.1%) did not follow the HEP, according to the findings of this survey. The demographics of the mothers revealed that 20-25-year-old mothers were more adherent than the other age groups. The findings of this study demonstrated that the physical therapist's treatment of the mother influenced exercise compliance.

Al-based fluoroperovskites compounds AlMF 3 (M = Cr, B) are investigated computationally and calculated their elastic, structural, optical, and electrical properties in this study utilising TB-MBJ potential (also GGA+U for AlCrF 3 ) approximations, according to the Birch Murnaghan Equation curve and tolerance factor, these material are structurally cubic and stable. The IRelast algorithm is used to forecast elastic properties, and the outputs show that these compound are mechanically stable, anisotropic and ductile. AlBF 3 has a metallic nature and overlapping states, while AlCrF 3 have a narrow indirect band gap at (X-M) points of symmetry, with band gaps of 0.71 eV for AlCrF 3 and zero eV for AlBF 3 . The partial and total density of states are being used to determine the influences of different basic states to the conduction and valence bands (TDOS & PDOS). Investigation of Optical properties shows that these compounds have low refractive index and high absorption coefficient, conductivity, reflective coefficient at high energy ranges. Owing to the indirect band gap, the applications of these compounds are deemed in conducting industries. Here we are using these compounds for first time and are examined using the computational method, which delivers a complete view into the different properties.

Antagonism of transient receptor potential vanniloid-1 (TRPV1) and desensitization of transient receptor potential ankyrin-1 (TRPA1) nociceptors alleviate inflammatory bowel diseases (IBD)-associated chronic pain. However, there is limited literature available about their role in regulating the mucosal layer, its interaction with host physiology, and luminal microbial community. The present study focuses on the effects' intra rectal administration of capsazepine (modulator of TRPA1/TRPV1 expressing peptidergic sensory neurons) on colonic mucus production and gut health. We performed histological analysis, gut permeability alteration, gene expression changes, metabolite profiling, and gut microbial abundance in the ileum, colon, and cecum content of these animals. Intra rectal administration of capsazepine modulates TRPA1/TRPV1-positive nociceptors (behavioral pain assays) and resulted in damaged mucosal lining, increased gut permeability, and altered transcriptional profile of genes for goblet cell markers, mucus regulation, immune response, and tight junction proteins. The damage to mucosal lining prevented its role in enterosyne (short chain fatty acids) actions. These results suggest that caution must be exercised before employing TRPA1/TRPV1 modulation as a therapeutic option to alleviate pain caused due to IBD.

This work displays the structural, electronic, elastic, optical, and magnetic properties in spin-polarized configurations for cubic fluoroperovskite ABF3 (A = Tl, B = Nb, V) compounds studied by density functional theory (DFT) by means of the Tran-Blaha-modified Becke-Johnson (TB-mBJ) approach. The ground state characteristics of these compounds, i.e., the lattice parameters a0, bulk modulus (B), and its pressure derivative B' are investigated. The structural properties depict that the selected compounds retain a cubic crystalline structure and have stable ground state energy. Electronic-band structures and DOS (density of states) in spin-polarized cases are studied which reports the semiconducting nature of both materials. The TDOS (total density of states) and PDOS (partial density of states) studies in both spin configurations show that the maximum contributions of states to the different bands is due to the B-site (p-states) atoms as well as F (p-states) atoms. Elastic properties including anisotropy factor (A), elastic constants, i.e., C 11 , C 12 , and C 44 , Poisson's ratio (υ), shear modulus and (G), Young's modulus (E) are computed. In terms of elastic properties, the higher (bulk modulus) "B" and ratio of "B/G" yield that these materials exhibit a ductile character. Magnetic properties indicate that both the compounds are ferromagnetic. In addition, investigations of the optical spectra including the real (ε1ω) and imaginary (ε2ω) component of the dielectric function, refractive index nω, optical reflectivity Rω, optical conductivity σω, absorption coefficient αω, energy loss function Lω, and electron extinction coefficient kω are carried out which shows the transparent nature of TlVF3 and TlNbF3. Based on the reported research work on these selected materials, their applications can be predicted in many modern electronic gadgets.

This paper explains our first-principle computational investigation regarding the structural, optical, elastic, and electrical characteristics of gallium-based GaMF 3 (M = Be and Ge) perovskite-type (halide-perovskite) compounds. Our current computation is based on density functional theory (DFT) and is achieved with the help of the WIEN2k code. We used the Birch-Murnaghan equation for optimization; in both compounds, we found that both GaBeF 3 and GaGeF 3 compounds are structurally stable. For the computation of elastic characteristics, the IRelast package for calculating elastic constants (ECs) is utilized. These compounds are mechanically ductile, scratch-resistant, anisotropic, and mechanically stable, showing huge opposition to plastic strain. The modified Becke-Johnson (TB-mBJ) potential approximation method is used to calculate different physical characteristics and shows that GaGeF 3 behaves as a metal, whereas the GaBeF 3 compound is insulating in nature. The involvement of various electronic states in band structures is calculated using the theory of the density of states. The different optical properties of these compounds can be studied easily using their band gap energy. At high energy ranges, these substances demonstrate strong absorption. At low energies, the GaGeF 3 compound is transparent, while the GaBeF 3 compound is opaque to incoming photons. Investigation of the optical characteristics has led us to the conclusion that both GaGeF 3 and GaBeF 3 compounds can be used for high-frequency ultraviolet device applications. This computational work is considered to be the first time that we can study these compounds, which to our knowledge have not previously been experimentally validated.

Erosion of the elbow due to non-Newtonian viscous slurry flows is often observed in hydrocarbon transportation pipelines. This paper intends to study the erosion behavior of double offset U-bends and 180° U-bends for two-phase (liquid-sand) flow. A numerical simulation was conducted using the Discrete Phase Model (DPM) on carbon steel pipe bends with a 40 mm diameter and an R/D ratio of 1.5. The validity of the erosion model has been established by comparing it with the results quantified in the literature by experiment. While the maximum erosive wear rates of all evaluated cases were found to be quite different, the maximum erosion locations have been identified between 150° and 180° downstream at the outer curvature. It was seen that with the increase in disperse phase diameter, the erosive wear rate and impact area increased. Moreover, with the change of configuration from a 180° U-bend to a double offset U-bend, the influence of turbulence on the transit of the disperse phase decreases as the flow approaches downstream and results in less erosive wear in a double offset U-bend. Furthermore, the simulation results manifest that the erosive wear increases with an increase in flow velocity, and the erosion rate of the double offset U-bend was nearly 8.58 times less than the 180° U-bend for a carrier fluid velocity of 2 m/s and 1.82 times less for 4 m/s carrier fluid velocity. The erosion rate of the double offset U-bend was reduced by 120% compared to the 180° U-bend for 6 m/s in liquid-solid flow.

Drought stress is a major abiotic stress that hinders plant growth and development. Brassinosteroids (BR), including 2,4-epibrassinolide (EBR), play important roles in plant growth, development, and responses to abiotic stresses, including drought stress. This work investigates exogenous EBR application roles in improving drought tolerance in tobacco. Tobacco plants were divided into three groups: WW (well-watered), DS (drought stress), and DSB (drought stress + 0.05 mM EBR). The results revealed that DS decreased the leaf thickness (LT), whereas EBR application upregulated genes related to cell expansion, which were induced by the BR ( DWF4 , HERK2 , and BZR1 ) and IAA ( ARF9 , ARF6 , PIN1 , SAUR19 , and ABP1 ) signaling pathway. This promoted LT by 28%, increasing plant adaptation. Furthermore, EBR application improved SOD (22%), POD (11%), and CAT (5%) enzyme activities and their related genes expression ( FeSOD , POD , and CAT ) along with a higher accumulation of osmoregulatory substances such as proline (29%) and soluble sugars (14%) under DS and conferred drought tolerance. Finally, EBR application augmented the auxin (IAA) (21%) and brassinolide (131%) contents and upregulated genes related to drought tolerance induced by the BR ( BRL3 and BZR2 ) and IAA ( YUCCA6 , SAUR32 , and IAA26 ) signaling pathways. These results suggest that it could play an important role in improving mechanisms of drought tolerance in tobacco., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Over the past few decades, gene therapy has gained immense importance in medical research as a promising treatment strategy for diseases such as cancer, AIDS, Alzheimer's disease, and many genetic disorders. When a gene needs to be delivered to a target cell inside the human body, it has to pass a large number of barriers through the extracellular and intracellular environment. This is why the delivery of naked genes and nucleic acids is highly unfavorable, and gene delivery requires suitable vectors that can carry the gene cargo to the target site and protect it from biological degradation. To date, medical research has come up with two types of gene delivery vectors, which are viral and nonviral vectors. The ability of viruses to protect transgenes from biological degradation and their capability to efficiently cross cellular barriers have allowed gene therapy research to develop new approaches utilizing viruses and their different genomes as vectors for gene delivery. Although viral vectors are very efficient, science has also come up with numerous nonviral systems based on cationic lipids, cationic polymers, and inorganic particles that provide sustainable gene expression without triggering unwanted inflammatory and immune reactions, and that are considered nontoxic. In this review, we discuss in detail the latest data available on all viral and nonviral vectors used in gene delivery. The mechanisms of viral and nonviral vector-based gene delivery are presented, and the advantages and disadvantages of all types of vectors are also given.

Protein kinases play an essential role in plants' responses to environmental stress signals. SnRK2 (sucrose non-fermenting 1-related protein kinase 2) is a plant-specific protein kinase that plays a crucial role in abscisic acid and abiotic stress responses in some model plant species. In apple, corn, rice, pepper, grapevine, Arabidopsis thaliana , potato, and tomato, a genome-wide study of the SnRK2 protein family was performed earlier. The genome-wide comprehensive investigation was first revealed to categorize the SnRK2 genes in the Liriodendron chinense (L . chinense) . The five SnRK2 genes found in the L. chinense genome were highlighted in this study. The structural gene variants, 3D structure, chromosomal distributions, motif analysis, phylogeny, subcellular localization, cis-regulatory elements, expression profiles in dormant buds, and photoperiod and chilling responses were all investigated in this research. The five SnRK2 genes from L . chinense were grouped into groups (I-IV) based on phylogeny analysis, with three being closely related to other species. Five hormones-, six stress-, two growths and biological process-, and two metabolic-related responsive elements were discovered by studying the cis-elements in the promoters. According to the expression analyses, all five genes were up- and down-regulated in response to abscisic acid (ABA), photoperiod, chilling, and chilling, as well as photoperiod treatments. Our findings gave insight into the SnRK2 family genes in L. chinense and opened up new study options., Competing Interests: The authors declare no conflict of interest.

Neuroendocrine prostate cancer (NEPC) represents a highly aggressive form of prostate tumors. NEPC results from trans-differentiated castration-resistant prostate cancer (CRPC) with increasing evidence indicating that the incidence of NEPC often results from the adaptive response to androgen deprivation therapy. Recent studies have shown that a subset of NEPC exhibits overexpression of the MYCN oncogene along with the loss of tumor suppressing TP53 and RB1 activities. N-MYC is structurally disordered with no binding pockets available on its surface and so far, no clinically approved drug is available. We adopted a drug-repurposing strategy, screened ~1800 drug molecules, and identified fludarabine phosphate to preferentially inhibit the proliferation of N-MYC overexpressing NEPC cells by inducing reactive oxygen species (ROS). We also show that fludarabine phosphate affects N-MYC protein levels and N-MYC transcriptional targets in NEPC cells. Moreover, enhanced ROS production destabilizes N-MYC protein by inhibiting AKT signaling and is responsible for the reduced survival of NEPC cells and tumors. Our results indicate that increasing ROS production by the administration of fludarabine phosphate may represent an effective treatment option for patients with N-MYC overexpressing NEPC tumors.

Effective child protection systems and processes require reliable and accurate data. The aim of this study was to determine what data could be extracted from hospital records in a single site that reflected a child's journey from admission with suspected abuse to the decisions regarding substantiation made by the multidisciplinary child protection team. A retrospective study of the case records of 452 children referred to a major UK children's tertiary centre for suspected child maltreatment was undertaken. Child maltreatment was substantiated in 65% of referred cases, with the majority of referrals coming from children living in the most deprived neighbourhoods in the country. Domestic violence and abuse and the child's previous involvement with statutory bodies were associated with case substantiation. Physical abuse predominated, with soft tissue injuries, including dog bites and burns, most frequent. Burns were related almost exclusively to supervisory neglect. There were also cases of medical neglect. Emotional abuse was associated with exposure to domestic violence and abuse and to self-harm. The strengths and limitations for single-centre data systems were explored, concluding with a recommendation to establish an agreed national and international minimum data set to protect children from maltreatment.

Nowadays, the use of statistical approaches, i.e., Box-Bhenken designs, are becoming very effective for developing and optimizing pharmaceutical drug formulations. In the current work, a Box-Bhenken design was employed using Design Expert version 11 to develop, evaluate, and optimize a hydrogel-based formulation for sustained release of an antiviral drug, i.e., favipiravir. The hydrogels were prepared using the free radical polymerization technique. β-Cyclodextrin (β-CD), N , N '-methylenebisacrylamide (MBA), acrylic acid (AA), and potassium per sulfate (KPS) were used as oligomer, crosslinker, monomer, and initiator, respectively. Three variables, including β-CD (X 1 ), MBA (X 2 ), and AA (X 3 ) were used at various concentrations for the preparation of hydrogels, followed by evaluation of a sol-gel fraction, swelling, porosity, chemical compatibilities, in vitro drug release, and entrapment efficiency. The results of the studies revealed that the degree of swelling was pH dependent, the best swelling being at pH 7.2 (1976%). On the other hand, for the low sol fraction of 0.2%, the reasonable porosity made the hydrogel capable of loading 99% favipiravir, despite its hydrophobic nature. The maximum entrapment efficiency (99%) was observed in optimized hydrogel formulation (F15). Similarly, in vitro drug release studies showed that the prepared hydrogels exhibited a good, sustained release effect till the 24th hour. The kinetic modelling of drug release data revealed that the Korsmeyer-Peppas model was best fit model, describing a diffusion type of drug release from the prepared hydrogels. Conclusively, the outcomes predict that the hydrogel-based system could be a good choice for developing a sustained-release, once-daily dosage form of favipiravir for improved patient compliance.

Newly designed series of indole-containing pyrazole analogs, pyrazolinylindoles, were synthesized, and their structures were confirmed based on the spectral data of the 1 H NMR, 13 C NMR, and HR-MS analyses. Preliminary anti-cancer activity testings were carried out by the National Cancer Institute, United States of America (NCI, USA). Compounds HD02, HD05, and HD12 demonstrated remarkable cytotoxic activities against nine categories of cancer types based cell line panels which included leukemia, colon, breast, melanoma, lungs, renal, prostate, CNS, and ovarian cancer cell lines. The highest cytotoxic effects were exhibited by the compounds HD02 [1-(5-(1-H-indol-3-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenylethanone], HD05 [1-(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenoxyethanone], and HD12 [(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanone] against some of the 56 types of NCI-based cell lines in different panels. Compound HD05 showed the maximum range of cancer cell growth inhibitions against all categories of the cell lines in all nine panels. On average, in comparison to the referral standard, imatinib, at a dose level of 10 µM, the HD05 showed significant activity against leukemia in the range of 78.76%, as compared to the imatinib at 9% of cancer cells' growth inhibitions. Molecular docking simulation studies were performed in silico on the epidermal growth factor receptor (EGFR) tyrosine kinase, in order to validate the activity.

Sucrose (Suc) accumulation is one of the key indicators of leaf senescence onset, but little is known about its regulatory role. Here, we found that application of high (120-150 mM) and low levels (60 mM) of Suc to young leaf (YL) and fully expanded leaf (FEL) discs, respectively, decreased chlorophyll content and maximum photosynthetic efficiency. Electrolyte leakage and malondialdehyde levels increased at high Suc concentrations (90-120 mM in YL and 60 and 150 mM in FEL discs). In FEL discs, the senescence-associated gene NtSAG12 showed a gradual increase in expression with increased Suc application; in contrast, in YL discs, NtSAG12 was upregulated with low Suc treatment (60 mM) but downregulated at higher levels of Suc. In YL discs, trehalose-6-phosphate (T6P) accumulated at a low half-maximal effective concentration (EC50) of Suc (1.765 mM). However, T6P levels declined as trehalose 6 phosphate synthase (TPS) content decreased, resulting in the maximum velocity of sucrose non-fermenting-1-related protein kinase (SnRK) and hexokinase (HXK) occurring at higher level of Suc. We therefore speculated that senescence was induced by hexose accumulation. In FEL discs, the EC50 of T6P occurred at a low concentration of Suc (0.9488 mM); T6P levels progressively increased with higher TPS content, which inhibited SnRK activity with a dissociation constant ( K d ) of 0.001475 U/g. This confirmed that the T6P-SnRK complex induced senescence in detached FEL discs.

Non-obstructive azoospermia (NOA), characterized by spermatogenesis failure and the absence of sperm in ejaculation, is the most severe form of male infertility. However, the etiology and pathology between meiosis-associated monogenic alterations and human NOA remain largely unknown. A homozygous MSH5 mutation (c.1126del) was identified from two idiopathic NOA patients in the consanguineous family. This mutation led to the degradation of MSH5 mRNA and abolished chromosome axial localization of MutSγ in spermatocytes from the affected males. Chromosomal spreading analysis of the patient's meiotic prophase I revealed that the meiosis progression was arrested at a zygotene-like stage with extensive failure of homologous synapsis and DSB repair. Therefore, our study demonstrates that the MSH5 c.1126del could cause meiotic recombination failure and lead to human infertility, improving the genetic diagnosis of NOA clinically. Furthermore, the study of human spermatocytes elucidates the meiosis defects caused by MSH5 variant, and reveals a conserved and indispensable role of MutSγ in human synapsis and meiotic recombination, which have not previously been well-described.