Search

Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by progressive memory loss. Although AD neuropathological hallmarks are extracellular amyloid plaques and intracellular tau tangles, the best correlate of disease progression is synapse loss. What causes synapse loss has been the focus of several researchers in the AD field. Synapses become dysfunctional before plaques and tangles form. Studies based on early-onset familial AD (eFAD) models have supported that synaptic transmission is depressed by β-amyloid (Aβ) triggered mechanisms. Since eFAD is rare, affecting only 1% of patients, research has shifted to the study of the most common late-onset AD (LOAD). Intracellular trafficking has emerged as one of the pathways of LOAD genes. Few studies have assessed the impact of trafficking LOAD genes on synapse dysfunction. Since endocytic traffic is essential for synaptic function, we reviewed Aβ-dependent and independent mechanisms of the earliest synaptic dysfunction in AD. We have focused on the role of intraneuronal and secreted Aβ oligomers, highlighting the dysfunction of endocytic trafficking as an Aβ-dependent mechanism of synapse dysfunction in AD. Here, we reviewed the LOAD trafficking genes APOE4, ABCA7, BIN1, CD2AP, PICALM, EPH1A, and SORL1, for which there is a synaptic link. We conclude that in eFAD and LOAD, the earliest synaptic dysfunctions are characterized by disruptions of the presynaptic vesicle exo- and endocytosis and of postsynaptic glutamate receptor endocytosis. While in eFAD synapse dysfunction seems to be triggered by Aβ, in LOAD, there might be a direct synaptic disruption by LOAD trafficking genes. To identify promising therapeutic targets and biomarkers of the earliest synaptic dysfunction in AD, it will be necessary to join efforts in further dissecting the mechanisms used by Aβ and by LOAD genes to disrupt synapses.

CD2-associated protein (CD2AP) was identified as a genetic risk factor for late-onset Alzheimer’s disease (LOAD). However, it is unclear how CD2AP contributes to LOAD synaptic dysfunction underlying AD memory deficits. We have shown that loss of CD2AP function increases β-amyloid (Aβ) endocytic production, but it is unknown whether it contributes to synapse dysfunction. As CD2AP is an actin-binding protein, it may also function in F-actin-rich dendritic spines, which are the excitatory postsynaptic compartments. Here, we demonstrate that CD2AP colocalizes with F-actin in dendritic spines of primary mouse cortical neurons of both sexes. Cell-autonomous depletion of CD2AP specifically reduces spine density and volume, resulting in a functional decrease in synapse formation and neuronal network activity. Postsynaptic reexpression of CD2AP, but not blocking Aβ production, is sufficient to rescue spine density. CD2AP overexpression increases spine density, volume, and synapse formation, while a rare LOAD CD2AP mutation induces aberrant F-actin spine-like protrusions without functional synapses. CD2AP controls postsynaptic actin turnover, with the LOAD mutation in CD2AP decreasing F-actin dynamicity. Our data support that CD2AP risk variants could contribute to LOAD synapse dysfunction by disrupting spine formation and growth by deregulating actin dynamics. [ABSTRACT FROM AUTHOR]

Introduction: Durum wheat (Triticum turgidum L. var. durum) is the second most crucial wheat and the tenth main crop globally. Salinity stress prevents water absorption from the soil and disturbs the ionic balance of the cell. As a result, metabolic processes such as seed germination, seedling growth, flowering, and seed formation are inhibited. The purpose of this study is to the evaluation of the effects of salinity stress on the germination and seedling growth of different durum wheat genotypes, as well as to identify and select tolerant genotypes using multivariate selection indices such as the ideal genotype selection index (IGSI) and the multi-trait genotype--ideotype distance index (MGIDI). Materials and methods: In this research, 50 different durum wheat lines and genotypes were prepared by the Agricultural Research, Education and Extension Organization of Iran and were evaluated in terms of tolerance to salinity in the germination stage, as a factorial experiment, based on a completely randomized design with three replications. Salinity levels included 0, 75, 150, and 300 mM sodium chloride concentrations. After one day, counting the number of germinated seeds was started daily. Based on the data obtained from counting the germinated seeds, various parameters of seed germination, including coefficient of the velocity of germination (CVG), germination index (GI), average germination duration (MGT), average daily germination (MDG) and final germination percentage (FGP) were calculated. In addition, after ten days, the characteristics such as root and shoot length and dry weight of root and shoot were measured for each genotype. Also, using the seedling height and dry weight, and the seed germination percentage, the seedling vigor was calculated. The MGIDI index of the studied genotypes was calculated based on factor scores of the first three factors with eigenvalues greater than one in factor analysis based on principal component analysis (PCA). The IGSI index also was calculated considering all the traits. Results and discussion: The analysis of variance showed significant differences (p < 0.01) between salinity levels and between genotypes in terms of all traits. But, the interaction effect of salinity x genotype was not significant for all studied traits. The comparison of the salinity levels showed that the germination components and the length and weight of the root and shoot decreased by increasing salinity levels. Factor analysis based on principal component analysis (PCA) showed that in normal conditions and salinity (150 mM NaCl) stress conditions, the first three factors with eigenvalues greater than one explained 83.89 and 84.97 percent of the total variance among the traits, respectively. According to the MGIDI index, under normal conditions based on the selection intensity of 30%, genotypes G30, G39, G51, G19, G14, G2, G31, G34, G5, G48, G7, G26, G1, G23, and G33 have the lowest values and were favorable. In 150 mM salinity condition, genotypes G9, G2, G29, G5, G12, G47, G30, G1, G31, G10, G34, G41, G13, G49, and G16 were the best genotypes with the lowest MGIDI values. According to the IGSI index in the 150 mM salinity level, genotypes G5, G29, G2, G30, G23, G9, G12, G1, G10, G41, G47, G34, G48, G16, and G13 have the highest values (between 0.60 to 0.80) were considered as desirable genotypes. On the contrary, genotypes G43, G46, G4, G26, G15, G19, G8, G14, G35, G44, G24, and G42, having IGSI values less than 0.40, were considered weak genotypes in this condition. Conclusion: In this study, IGSI and MGIDI indices were used to evaluate the response of different durum wheat genotypes to salinity using all studied traits. In general, the results of the present research showed a considerable genetic diversity among the studied durum wheat genotypes in terms of salinity tolerance at the germination stage, which can be used in the breeding programs of this valuable crop. Also, the IGSI and the MGIDI indices were effective in identifying superior genotypes based on all the studied traits. Using these indices in breeding programs to select desirable genotypes can be fruitful and effective. [ABSTRACT FROM AUTHOR]

Introduction: Water limitation is one of the most important abiotic factors that can limit plant growth and yield due to production of reactive oxygen species (ROS) like H2O2 and the reduction of chlorophyll content. To protect against oxidative stress, plant cells produce both antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POX), and non-enzymatic antioxidants such as low weight molecules like proline, sugars and ascorbate. Also water limitation disturbs the mineral-nutrient relations in plants through their effects on nutrient availability and numerous of physiological and biochemical destruction in the vegetative and reproductive periods of plant development. Several strategies have been suggested in order to improve yield under abiotic and biotic stresses in plants, among them application of Plant Growth Promoting Rhizobacteria (PGPR) and nano particles such as nano iron-silicon oxide play a key role in yield improvement. A better understanding of physiological responses under water limitation may help in programs which the objective is to improve the drouht resistance of crop. During the course of these stresses, active solute accumulation of compatible solutes such as proline and the activities CAT, POD and PPO enzymes are claimed to be an effective stress tolerance mechanism. Therefore, the aim of this study was to evaluate the effects of bio-fertilizers and nano iron oxide and nano oxide on some physiological and biochemical (i.e., antioxidant enzyme activity, chlorophyll, protein, soluble sugars and proline) responses of triticale under water limitation conditions. Materials and methods: An experiment was conducted as factorial based on randomized complete block design with three replicates at the research farm of faculty of Agriculture and Natural Resources, University of Mohaghegh Ardabili in 2021. The experimental factors were included of irrigation in three levels (full irrigation as control, irrigation withholding at 50% of booting and heading stages as severe and moderate water limitation respectively (BBCH 43 and 55 respectively), application of bio fertilizers in four levels (no application as control, application of Azospirilum, Pseudomonas, both application Azospirilum and Pseudomonas) and nanoparticles foliar application at four levels (foliar application with water as control, nano iron oxide foliar application (1 g.l-1), nano silicon oxide (50 mg.l-1), both application nano iron-silicon oxide). Psedomunas and Azospirilum were isolated from the rhizospheres of wheat by Research Institute of Soil and Water, Tehran, Iran. For inoculation seeds were coated with gum Arabic as an adhesive and rolled into the suspension of bacteria until uniformly coated. The strains and cell densities of microorganisms used as PGPR in this experiment were 1x108 colony forming units (CFU). In each plot there were 5 rows with 2 m long. In each experimental plot, two marginal rows and 0.5 m from beginning and ending of planting lines were removed data were measured from the middle lines. The used nano silicon-iron oxide had the average particle size less than 30 nm and special surface of particles was more than 30 m2.g-1. They were product of Nanomaterial US Research which was provided by Pishgaman Nanomaterials Company of Iran. Nano iron oxide and nano silicon powder added to deionized water and was placed on ultra sonic equipment (100 W and 40 kHz) on a shaker for better solution. Foliar application of nano silicon oxide and putrecine were done in two stages of period growth BBCH 21 and 30. Results and discussion: The results showed that total chlorophyll content (48.16%), quantum yield (36.05%), relative water content (35.83%) and grain yield (43.28%) increased in dual application of bio fertilizers and nano particles foliar application under full irrigation conditions compared to no application of bio fertilizers and nano particles under irrigation cut off at booting stage. But under such conditions, electrical conductivity, hydrogen peroxide and malondialdehyde content decreased 35.67, 53.16 and 56.32% respectively compared to no application of PGPR and nanoparticles under irrigation withholding in booting stage. Also, the application of PGPR and nanoparticles under irrigation cut off in booting stage increased the activity of catalase, peroxidase and polyphenol oxidase enzymes (47.06, 55.69 and 36.53% respectively), proline and soluble sugars content (45.41 and 46.93% respectively) compared to no application of PGPR and nanoparticles under full irrigation conditions. Conclusion: Based on the results of this study, the application of plant growth promoting rhizobacteria and nonoparticle can increase grain yield of triticale under water limitation conditions due to improving biochemical and physiological traits. [ABSTRACT FROM AUTHOR]

Abstract Magnetic supported ionic liquids are a unique subclass of ionic liquids that possess the ability to respond to external magnetic fields, combining the advantageous properties of traditional ILs with this magnetic responsiveness. A novel magnetic ionic nanocatalyst of Fe3O4@SiO2@CPTMS-DTPA was prepared by anchoring an ionic liquid, CPTMS-DTPA, onto the surface of silica-modified Fe3O4. The morphology, chemical structure and magnetic property of the magnetic ionic nanocatalyst structure was characterized using scanning electron microscopy, X-ray powder diffraction, Fourier transformation infrared spectroscopy, vibrating sample magnetometer, and thermogravimetric analysis. The results confirmed the successful attachment of the ionic liquid to the magnetic substrate. Subsequently, the magnetic nanocatalyst was employed for the green synthesis of α-aminophosphonate derivatives. The synthesis was achieved via a one-pot, three-component reaction involving various aldehydes, amines, and different trialkyl(aryl) phosphite derivatives. The reactions were conducted under ultrasound conditions for a duration of 10–25 min, resulting in good to excellent product yields (64–97%). Its recyclability was tested for up to five cycles using magnetic separation which makes it a highly efficient method for quickly separating catalysts from the reaction medium without compromising catalytic activity.

Abstract Aim We assessed the impact of a 3-year change-percent in adiposity measures on regression and pre-diabetes (Pre-DM) progression among Iranian adults. Methods Three-year change-percent in body weight (BW), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and visceral adiposity index (VAI) were calculated for 1458 Pre-DM subjects (mean age of 53.0 ± 13.7, 46.8% men), participated in the third examination of the Tehran Lipid and Glucose Study (2006–2008). Multinomial logistic regression models were used to estimate relative risk ratios (RRRs) of the outcomes [i.e., regression to normal glucose regulation (NGR), persistence in Pre-DM, and progression to newly diagnosed type 2 diabetes (T2D)] across 3-year change categories of adiposity measures (i.e., ≥ 5% decrease, 0–5% decrease, increase). Results Over nine years of follow-up, 37.7 and 39.0% returned to NGR and progressed to T2D, respectively. Decreased BW (0–5 and ≥ 5%) was associated with regression to NGR (RRRs = 1.44, 95% CIs = 1.05–1.98, and 2.64, 1.63–4.28, respectively). Decreased BMI and WC ≥ 5% were also associated with regression to NGR (RRRs = 1.63, 95% CI = 1.01–2.64; 1.69, 1.20–2.37, respectively). Changes in WHR and VAI were not associated with Pre-DM regression or progression. Pre-DM subjects with ≥ 5% BW loss had a constant FSG level overtime and a lower overall mean of FSG (116 vs. 111 and 112 mg/dL, P = 0.023 and 0.009, respectively) and 2 h-SG (154 vs. 165 and 168 mg/dL) compared to those had 0–5% BW loss or BW gain. Conclusion Short-term management of adiposity measures increases the regression probability to NGR. Targeting BW loss seems a more potent predictor of Pre-DM reversion among the adiposity measures.

Abstract It is critical to understand the impact of significant physiological changes during pregnancy on the extent of maternal and fetal drug exposure. Fostemsavir (FTR) is a prodrug of temsavir (TMR) and is approved in combination with other antiretrovirals for multi‐drug‐resistant human immunodeficiency virus (HIV) infections. This physiologically based pharmacokinetic model (PBPK) study was used to estimate TMR PK in pregnant populations during each trimester of pregnancy to inform FTR dosing. A PBPK model was developed and validated for TMR using PK data collected following intravenous TMR and oral FTR dosing (immediate‐release and extended‐release tablets) in healthy volunteers. Predicted TMR concentration–time profiles accurately predicted the reported clinical data and variability in healthy (dense data) and pregnant (sparse data) populations. Predicted versus observed TMR geometric mean (CV%) clearance following intravenous administration was 18.01 (29) versus 17 (21) (L/h). Predicted versus observed TMR AUC0–inf (ng.h/mL) in healthy volunteers following FTR administration of the extended‐release tablet were 9542 (66) versus 7339 (33). The validated TMR PBPK model was then applied to predict TMR PK in a population of pregnant individuals during each trimester. Simulations showed TMR AUC in pregnant individuals receiving FTR 600 mg twice daily was decreased by 25% and 38% in the second and third trimesters, respectively. However, TMR exposure remained within the range observed in nonpregnant adults with no need for dose adjustment. The current PBPK model can also be applied for the prediction of local tissue concentrations and drug–drug interactions in pregnancy.

This study discusses the impacts of misinformation on social cohesion, trust, and well-being, particularly when targeting specific racial and ethnic groups. It categorizes and reviews various articles to identify the sources and types of misinformation on social media, highlighting common themes and origins. The study briefly acknowledges that generative artificial intelligence and machine learning tools can increase the chance of the generation and spread of harmful misinformation across digital platforms. It also highlights the importance of digital and media literacy education in helping individuals critically evaluate information and navigate online spaces responsibly. Promoting racial and ethnic digital literacy is crucial for protecting against misinformation and fostering informed, representative online discourse. The study calls for a multifaceted approach centered on trust, transparency, and accountability in addressing social media misinformation. Ultimately, it advocates for a culture of critical thinking, factchecking, and ethical behavior to create an online environment that respects diversity, inclusion, and truth, thereby contributing to an informed and empowered society.

This paper introduces a novel method for automatically classifying questions with multiple labels, using data specifically sourced from Stack Overflow. Traditional tagging methods frequently face challenges due to the complexity and semantic diversity of these questions, resulting in inconsistent and sometimes inaccurate results. The process starts with preprocessing to remove any unwanted elements. Next, we convert the questions into meaningful representations using SMPNet. The semantic vectors obtained are then processed using UMAP to help us understand the overall structure of the data and make it easier to cluster similar items. After dimensionality reduction with UMAP, we use the K-Means method to group the questions into clusters, with the best number of groups determined by the Silhouette Score. Finally, a fine-tuned DeBERTa model is trained for each cluster to accurately predict the appropriate tags. Our approach significantly outperforms traditional methods, achieving 2% improvement over the best baseline. This strategy improves model efficiency by narrowing the focus to specific subsets of data.

Abstract Carbamazepine is a pharmacological medication commonly prescribed to treat epilepsy. Dose adjustments, poor bioavailability, and prolonged side effects present significant challenges associated with its use. Poloxamer micelles have demonstrated exceptional properties as nanocarriers for drug delivery. This research aimed to develop Poloxamer nanomicelles containing carbamazepine and assess their potential to cross the blood–brain barrier. Poloxamer 407 and P-85 micelles, anchored with TAT as a ligand and containing carbamazepine, were prepared. The morphology, entrapment efficiency, drug release, stability, and toxicity of nanomicelles were examined, along with animal studies conducted to evaluate their anticonvulsant effects. The distribution of carbamazepine-Poloxamer in the brain and plasma was assessed. The results indicated the successful formation of spherical nanomicelles with an average size of less than 100 nm, and carbamazepine was effectively incorporated into the micelles. Formulations composed of mixtures of Poloxamer exhibited a high encapsulation efficiency of approximately 92.1% and remained stable for three months. A sustained release of carbamazepine was observed for up to 72 h. The anticonvulsant effect of carbamazepine-loaded nanomicelles in mice was found to be significantly greater than that of those treated with carbamazepine solution, with the effect increasing by approximately tenfold. Compared to free carbamazepine, the carbamazepine-loaded nanomicelles exhibited a 5.5-fold increase in the brain targeting index, with no toxicity observed in mice treated with these nanomicelles. These findings suggest that Poloxamer micelles represent a promising nanoscale, controlled-release delivery system that is free from toxicity and can enhance the penetration of carbamazepine into the brain while improving its anticonvulsant activity. Graphical Abstract

Introduction and purpose: Fleas are ectoparasites of birds and mammals. In addition to causing harassment due to their bites, these insects transmit some diseases, such as plague, endemic typhus, and tularemia, to humans. The present study aimed to identify the species and biodiversity of important fleas in Neka City (Mazandaran Province, Iran). The present research followed a descriptive-analytical approach. Methods: The sampling was performed for one year, from April to March 2022, in the rural areas of Neka City. In this study, 15 villages were randomly selected according to the geographic location of the north, south, east, west, and center. Different methods, including hand catch, human bait, and spreading white cloth, were employed to collect fleas. The collected samples were preserved in closed tubes containing 70% alcohol. After clarification and mounting in the laboratory, they were identified using validated identification keys. Results: A total of 2600 fleas were caught in this study, involving Ctenocephalides canis (30.93%), Ctenocephalides felis (57.54%), and Pulex irritans (11.53%) species. Among them, 33.12% were male, and 66.89% were female. The dominant species among the caught fleas was Ctenocephalides felis, and the majority of the collected fleas were caught in the Estakhr Posht village. Furthermore, the highest number of fleas caught was associated with the mountainous climate and occurred during spring. Conclusion: The results revealed that Ctenoscephalides felis is the dominant and most abundant species in Neka City, Iran, which can be considered a health concern. Therefore, their presence and frequency should be considered a serious issue, and appropriate control measures should be made.

Abstract In this paper, we study the existence and multiplicity of weak solutions of the p ( x ) $p(x)$ -Laplacian problems that are subject to Dirichlet boundary conditions, employing variational techniques as our primary analytical framework.

Abstract The research aimed to evaluate the antioxidative and antibacterial characteristics of aqueous sumac extract on methicillin-resistant Staphylococcus aureus through in-vitro and in-vivo study. Sumac extract has been obtained through the soaking method, and its antioxidant properties were gauged using the DPPH free radical scavenging method. The minimum inhibitory concentration (MIC) of sumac extract was determined on S. aureus obtained from hospitalized patients, as well as an assessment of biofilm-formation and the release of bacterial intracellular compounds. in vivo experimentation involved injecting bacteria (108 cfu/ml) into mice, which subsequently manifested indicators of symptoms of infection, and the number of bacteria within their bloodstream was quantified. The Sumac extract demonstrated strong antioxidant properties at concentrations of 1000 mg/ml. Furthermore, the agar tests for the gram staining, mannitol, coagulase, and DNase revealed that 190 cultured bacteria samples were identified as Staphylococcus aureus. These bacteria were resistant to clindamycin, ciprofloxacin, and methicillin antibiotics, but sensitive to erythromycin and penicillin antibiotics. Additionally, the bacteria displayed significant methicillin resistance and formed a strong biofilm (65.78%). The sumac extract showed a MIC range of 125–1000 µg/ml against Staphylococcus aureus. Treatment with concentrations above the MIC was found to prevent the formation of biofilm and increase the release of bacterial intracellular compounds. Sumac extract led to a decrease in bacterial count in the blood of mice and reduced signs of infection. Sumac extract demonstrated powerful antioxidant and antibacterial effects against resistant microorganisms, suggesting its potential as a promising compound for the treatment of resistant infections in future research.

Introduction: Ovarian cancer, as an aggressive epithelial tumor, remains one of the leading causes of cancer-related mortality in women. Regarding to the side effects of chemical drugs, medicinal plants, according to their unique properties such as cheapness, naturalness and availability, and without any significant side effects, medicinal plants have recently been considered in the prevention of diseases. In this laboratory research, the cytotoxic effect of hydroalkolic extract of Daphne mucronata Royle on cell viability of A2780 cancer cell and the expression of MAPK8 and PTK2 genes in the cells treated with the Ephedra plant extract during three-time interval 24,48 and 72 hours after treatment were investigated. Methods: The inhibitory effect of hydroalcholic extact of D. mucronato on targeted cells was done using MTTassay then, expression level of MAPK8 and PTK2 genes in cells treated with plant extract were investigated using qRT-PCR method. Data analyses were done using GraphPad prism software. Results: Regarding to the results of cell viability, IC50 rate for 24, 48 and 72h after treatment were determined as 105.40, 85.98 and 81.38µg/mL, respectively. Expression analysis of tested genes showed that hydroalcoholic plant extract of D. mucronato had not significant effect on expression of targeted genes (Pvalue≤0.05) so that there was no significant difference on their expression level compared to the control. Conclusion: According to the results, it can be concluded that D. mucronato extract had a significant inhibitory effect on treated A2870s cancer cells, but it was not able to change the expression level of genes involved in anticancer activities and its molecular pathways. The use of bio-markers and other gene pathways is suggested for additional studies.

Background: Given the various issues that Polycystic ovary syndrome (PCOS) can cause in women and the need to address its consequences and provide solutions to improve the course of the disease and alleviate its symptoms, the present study aimed to investigate the association between body image and eating disorders, anxiety, and depression in individuals with PCOS.Methods: This observational study was conducted on 150 girls with PCOS in Hamadan, Iran in 2023. Convenience sampling method was used to select unmarried girls of reproductive age with PCOS. The participants were asked to complete certain questionnaires, including demographic questionnaires, the eating disorders examination questionnaire (EDE-QS), the hospital anxiety and depression scale (HADS), and the body shape questionnaire (BSQ). The collected data were analyzed using Stata-13 software, with a significance level of P

This experimental study examined techniques of subtitling for the deaf and hard-of-hearing (SDH) from the point of viewers’ content comprehension and image recognition. Three groups of deaf and hard of hearing people (n = 78) participated in the study. The research focused on four parameters: speed of subtitles, speaker identification, emotion and sound indication. By selecting three usual techniques for each parameter, three subtitled versions of a movie were produced. Each group of participants watched one of the subtitled versions and comprehension and freeze-frame tests were employed to examine participants’ reception. Based on the results, except for the image recognition, there were significant differences among the techniques in terms of participants’ content comprehension. As for the techniques of speaker identification, color-coding caused significantly better content comprehension scores than tagging. Concerning sound comprehension, the three techniques were not significantly different from one another in terms of viewers’ content comprehension. Regarding emotion comprehension, the absence of information and emoticons helped the participants comprehend characters’ tone and mood better than emotion descriptions.

Aim: This in vitro study investigates the effects of Silver Diamine Fluoride (SDF) application on the shear bond strength (SBS) of resin composite to sound and demineralized human teeth using different adhesive systems. Methods: Eighty sound human third molars were sectioned, mounted in acrylic blocks, and prepared to expose a 2 mm thick dentin layer. The teeth were randomly divided into eight groups, each representing a combination of sound or demineralized dentin, SDF application, and adhesive system used. Demineralization was achieved using a pH cycling process. SDF was applied to the designated groups, followed by the use of either an etch-and-rinse or self-etch adhesive system. Resin composite was then applied, and the SBS was measured using a universal testing machine. Data were analyzed using three-way ANOVA and post-hoc tests to identify significant differences. Results: The application of SDF generally led to a significant decrease in bond strength (p 0.05). The bond strength in the demineralized group using Clearfil SE Bond showed no significant difference between SDF application and non-application (p > 0.05). Conclusion: SDF application can significantly reduce the bond strength of resin composite to dentin, with the effect being dependent on the type of adhesive system and the state of the dentin. Further in vivo studies are needed to validate these findings.

Background: Research has demonstrated the association between susceptibility to coronavirus disease 2019 (COVID-19) and single nucleotide polymorphisms (SNPs). On the other hand, the cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) serves as a pivotal inhibitory receptor with a substantial impact on the advancement of viral infections. Besides, the disintegrin and metalloproteinase33 (ADAM33) gene is associated with both asthma and heightened airway responsiveness. Hence, this investigation sought to elucidate the potential association between the CTLA-4 rs5742909 and ADAM33 rs2280091 SNPs and the fatality rate of COVID-19 across various variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: Both SNPs were genotyped with the PCR-RFLP assay in 1734 improved and 1450 deceased individuals. Results: Our obtained results revealed a significant association between the CTLA-4 rs5742909 C/T-T/T genotypes and increased mortality risk of COVID-19 in three different SARS-CoV-2 variants. The ADAM33 rs2280091 polymorphism demonstrated no significant association with COVID-19 mortality under various inheritance models. Nevertheless, subsequent adjustments for SARS-CoV-2 variants revealed a notable association between the GA genotype of ADAM33 rs2280091 and mortality rates specifically among individuals infected with the Delta variant. Conclusions: In summary, the prediction of COVID-19 severity could be facilitated through the utilization of the CTLA-4 rs5742909 marker. Conversely, in the case of ADAM33 rs2280091, such prognostication appears to be contingent upon the specific variants of the SARS-CoV-2 virus.