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Catharanthine, a component of the anticancer drug vinblastine along with vindoline, disrupts the cell cycle by interfering with mitotic spindle formation. Apart from their antioxidant properties, vinca alkaloids like catharanthine inhibit phosphodiesterase activity and elevate intracellular cAMP levels. The aim of this study was to investigate how catharantine affects apoptosis and autophagy. This study conducted experiments on HepG2 liver carcinoma cells with varying doses of catharanthine to evaluate cell death rates and viability and determine the IC50 concentration via MTT assays. The apoptotic and autophagic effects of catharanthine were assessed using flow cytometry with annexin V and PI staining, while the expression of autophagy-related genes was analyzed through quantitative PCR. Additionally, molecular docking and molecular dynamics simulations were employed to further investigate catharanthine's impact on autophagy mechanisms. The study showed that catharanthine reduced oxidative stress and triggered apoptosis in HepG2 cells in a dose-dependent manner. Catharanthine also upregulated the expression of autophagy-related genes like LC3, Beclin1, and ULK1. Notably, catharanthine increased sirtuin-1 levels, a known autophagy inducer, while decreasing Akt expression compared to untreated cells. Molecular docking results indicated rapamycin had a stronger binding affinity with FRB (−10.7 KJ/mol−1) than catharanthine (−7.3 KJ/mol−1). Additionally, molecular dynamics simulations revealed that catharanthine interacted effectively with the FRB domain of mTOR, displaying stability and a strong binding affinity, although not as potent as rapamycin. In summary, besides its cytotoxic and pro-apoptotic effects, catharanthine activates autophagy signaling pathways and induces autophagic necrosis by inhibiting mTOR. [ABSTRACT FROM AUTHOR]

Individuals with inborn errors of immunity face challenges in fertility, pregnancy, and genetic disorder transmission. Prenatal genetic counseling is crucial, especially in tribal societies with consanguineous unions. Ten families with confirmed inborn errors of immunity were studied, revealing diverse pregnancy decisions: An architect with autosomal dominant STAT-1 gain of function underwent prenatal diagnosis despite initial plans for preimplantation genetic diagnosis. In a consanguineous family, two children died from leukocyte adhesion deficiency type 1 because the father refused prenatal diagnosis. First cousins opted against terminating the second pregnancy, resulting in two children affected by Bruton disease. Another consanguineous couple, with two children afflicted by ataxia-telangiectasia, chose oocyte donation for their third child, ensuring a healthy birth. Recurrent pregnancy loss was observed in a mother subsequently diagnosed with ZAP70 deficiency. A mother with Wiskott-Aldrich syndrome child opted for in vitro fertilization, leading to a healthy birth post-prenatal diagnosis. A misdiagnosis of anaplastic anemia occurred in a family with multiple instances of Wiskott-Aldrich syndrome. A leukocyte adhesion deficiency type 1 case led to parental dissolution due to the father's refusal to acknowledge the condition. In a non-consanguineous couple, the father's diagnosis of TACI deficiency influenced the mother's decision to discontinue pregnancy post-prenatal diagnosis. Genetic diagnosis alone cannot optimize prenatal care for immune dysregulation disorders. Various factors, including patient education, societal norms, ethics, and economics, impact pregnancy decisions. Clinical immunologists must integrate these elements into guidance strategies to enhance patient outcomes. [ABSTRACT FROM AUTHOR]

Unlike breast and prostate cancers, which are specifically affected by estrogens or androgens, hepatocellular carcinoma has been reported to be influenced by both sex hormones. Given the coincidental differences of hepatocellular carcinoma in men and women, we investigated the effects of β-estradiol and testosterone on the cell cycle, apoptosis, and Wnt signaling in a model of hepatocellular carcinoma to understand the sex hormone-related etiology. To determine the effective concentration of both hormones, an MTT assay was performed. The effects of β-estradiol and testosterone on cell proliferation and death were evaluated by specific staining and flow cytometry. In addition, gene expression levels of estimated factors involved in GPC3-Wnt survival signaling were analyzed using quantitative real-time polymerase chain reaction. Both hormones inhibited hepatic cell proliferation through arresting the cell cycle at S/G2 and increased the apoptosis rate in HepG2 cells. Both hormones dose-dependently decreased GPC3, Wnt, and DVL expression levels as activators of the Wnt-signaling pathway. In the case of Wnt-signaling inhibitors, the effects of both hormones on WIF were negligible, but they increased DKK1 levels in a dose-dependent manner. In each of the effects mentioned above, β-estradiol was notably more potent than testosterone. In contrast to the primary hypothesis of the project, in which testosterone was considered a stimulating carcinogenic factor in HCC pathogenesis, testosterone inhibited the occurrence of HCC similarly to β-estradiol. However, this inhibitory effect was weaker than that of β-estradiol and requires further study. [ABSTRACT FROM AUTHOR]

Recently, more studies have focused on predicting plant response to livestock grazing by using plant functional traits as indicators to study species adaptation under grazing disturbance. This study examines how different types of plant diversity (taxonomic, phylogenetic, and functional diversity) and strategies (Competitive, Stress-tolerant, and Ruderal) respond to grazing intensity. The study was conducted in the Siah Bisheh Rangelands, located in the southeast of Mazandaran province, Iran. In the region, three adjacent sites were chosen for vegetation sampling. Each site had low and high grazing intensity (LG and HG) areas. For each site and grazing intensity, three 100 m transects were randomly placed. Along each transect, 5 plots (1 × 1 m2) were sampled at 20 m intervals, resulting in a total of 90 plots. The plant coverage was recorded for each plot. To assess the evolutionary relationship among the 76 and 66 species in LG and HG grazing intensities, respectively, a phylogenetic tree was generated. To estimate plant strategy and calculate the overall functional distance between species in this study, four quantitative traits were used: canopy height, leaf area, leaf dry matter content (LDMC), and specific leaf area (SLA). Additionally, three characteristics of CSR strategy classification (Competitive, Stress-tolerance, and Ruderal), were considered. To evaluate functional differences between the two groups with different grazing intensities, we computed functional indices for each sampling plot based on the relative cover of species. The communities subjected to two grazing intensities (LG and HG) were compared using the T-test with a significance level of 5%. The study found that higher grazing intensity caused a shift from the ruderal to the stress-tolerance strategy at both the species and community levels. Furthermore, increased grazing intensity led to a decrease in species richness and diversity, while increasing functional divergence, functional evenness, and community LDMC. Ultimately, stress-tolerant and ruderal strategies dominated under high and low grazing intensities, respectively. The study suggests that plant functional traits are essential in evaluating plant strategies. Analyzing traits like leaf size, SLA, and LDMC can help understand plant survival and growth in different ecosystems. These findings highlight the importance of considering grazing intensity when evaluating plant strategies and the need for further research on how different plant functional traits impact plant responses to grazing pressure. Understanding how various traits contribute to plant performance and ecosystem dynamics can inform decisions about conservation priorities and management strategies. Plant functional traits are a powerful tool for ecologists and conservationists. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the relationship between surgical zygomatic arch fracture reduction and mandibular movements in different fracture types. Materials and Methods: Fractures were classified according to the Yamamoto classification. The extent of zygomatic arch reduction after surgery was evaluated by measuring three reference points on both fractured and normal side both before and after surgery. The selected reference points were: the most anterior (A1), the most posterior (B1) and the midpoint (C1) relative to midsagittal plane on the fracture side and the same points on the normal side (a1, b1, c1). Mouth opening, movements to right and left were recorded in these patients. Results: The highest extent of zygomatic arch reduction was observed at the midpoint of the arch (p = 0.041). Surgery did not significantly alter other points of the zygomatic arch. The extent of reduction of the zygomatic arch was not significantly associated with mandibular movements. However, type of fracture correlated with lateral excursion to the right and left (p = 0.002 and p = 0.031, respectively). Conclusion: This study showed that the amount of post-surgical changes in zygomatic arch reduction was not significantly related to mandibular movements. In addition, the amount of lateral excursion two weeks after surgical correction of more severe types of zygomatic arch fractures was less compared with other fracture types. Patients with more severe fractures may need to be followed for a longer period of time in order to regain the normal mandibular movement range. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis is the most prevalent form of leishmaniasis worldwide. Although various anti-leishmanial regimens have been considered, due to the lack of efficacy or occurrence of adverse reactions, design and development of novel topical delivery systems would be essential. This study aimed to prepare artemether (ART)-loaded niosomes and evaluate their anti-leishmanial effects against Leishmania major. ART-loaded niosomes were prepared through the thin-film hydration technique and characterized in terms of particle size, zeta potential, morphology, differential scanning calorimetry, drug loading, and drug release. Furthermore, anti-leishmanial effect of the preparation was assessed in vitro and in vivo. The prepared ART-loaded niosomes were spherical with an average diameter of about 100 and 300 nm with high encapsulation efficiencies of > 99%. The results of in vitro cytotoxicity revealed that ART-loaded niosomes had significantly higher anti-leishmanial activity, lower general toxicity, and higher selectivity index (SI). Half-maximal inhibitory concentration (IC50) values of ART, ART-loaded niosomes, and liposomal amphotericin B were 39.09, 15.12, and 20 µg/mL, respectively. Also, according to the in vivo study results, ART-loaded niosomes with an average size of 300 nm showed the highest anti-leishmanial effects in animal studies. ART-loaded niosomes would be promising topical drug delivery system for the management of cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]

The coenzyme ubiquinone-10 (CoQ10) is not only an important part of the electron transport chain of the mitochondrial inner membrane but also has complex biological functions beyond mitochondrial respiration. It is a natural nutrient that is not only produced by the body but is also found in foods, such as meat, eggs, fish, and vegetable oils. Because some types of cancer reduce CoQ10 blood levels, the use of CoQ10 supplements is recommended for the treatment of cancer patients. The anti-cancer effects of CoQ10 supplementation have been reported in several cancers, including colon and breast cancer. CoQ10 scavenges free radicals to reduce oxidative stress and minimize tissue damage. CoQ10 protects the body from damage caused by chemotherapy drugs by reducing the production of inflammatory cytokines and other inflammatory factors. Recent studies suggest that CoQ10 may be a supplement to pharmacotherapy for hepatocellular carcinoma. This article examines the effects of CoQ10 in hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Plant microbial fuel cells (PMFC) have attracted great scholarly attention as a renewable energy source. These cells have three main components: anode, cathode chambers, and a proton exchange membrane. In this study, a dual-chamber plant microbial fuel cell system was designed using Cyperus papyrus and Shewanella oneidensis. The effects of various factors, including the size of the electrodes, the distance between the electrodes, and the inoculation volume of Shewanella oneidensis, on the ability of electricity generation, were scrutinized. The results indicated that increasing the size area of the electrodes from 2 × 2 to 4 × 4 and 6 × 6 cm2 caused an increase in the output voltage by 43% and 58%, respectively. The PMFC produced a maximum power of 240 mW, with a Coulombic efficiency ranging from 0.66 to 0.75%. The plant microbial fuel cell designed in this study seemed to have a high potential to remove wastewater contaminants. Based on the results, during five days of setting up the system, COD and BOD decreased by 61.75% and 93.16%, respectively, which shows that in addition to generating power, the designed PMFC had a high potential to remove wastewater contaminants. [ABSTRACT FROM AUTHOR]

Since the role of Nrf2 in cancer cell survival has been highlighted, the pharmacological modulation of the Nrf2-Keap1 pathway may provide new opportunities for cancer treatment. This study purposed to use ubiquinone (Q10) as an antioxidant and catharanthine alkaloid as a cAMP inducer suppressing HepG2 cells by reducing Nrf2 level. The effects of Q10 and catharanthine on HepG2 cells in terms of viability were analyzed by MTT test. MTT results were used to determine the effective concentration of both drugs for the subsequent treatment and analysis. Subsequently, the effects of Q10 and catharanthine in a single and combined manner on oxidant/antioxidant status, apoptosis, metastasis, and drug resistance of HepG2 cells were investigated by related methods. Both Q10 and catharanthine decreased the level of oxidative stress products and increased antioxidant capacity in HepG2 cells. Nrf2 gene expression decreased by Q10, but catharanthine unexpectedly increased it. Following Nrf2 alterations, the expression levels of MMP-9 and MRP1 involved in metastasis and drug resistance were significantly and dose-dependently decreased by Q10, while catharanthine slightly increased both. However, both drugs increased caspase 3/7 activity and apoptosis rate, and the effect of Q10 on apoptosis was stronger than that of catharanthine. Most of the effects of the combination treatments were similar to those of the Q10 single treatment and indicated the dominant effect over the catharanthine component. Despite the antioxidant and apoptotic properties of both agents, Q10 was better than catharanthine in inducing apoptosis, counteracting drug resistance, and metastasis in HepG2 cells. [ABSTRACT FROM AUTHOR]

Purpose: Pyrus boissieriana is a rich source of arbutin and has been used in herbal medicine to treat infectious diseases. This study aimed to investigate the effect of the arbutin-rich fraction of Pyrus boissieriana aerial parts on Toxoplasma gondii In Vitro and In Vivo. Methods: An arbutin-rich fraction of P. boissieriana was prepared beforehand. Flow cytometry was used to evaluate the effect of different concentrations (1–512 µg/ml) of the P. boissieriana arbutin-rich fraction on Toxoplasma tachyzoites (RH strain). The cytotoxicity of the concentrations on the macrophage J774 cell line was also investigated by MTT assay. For In Vivo investigation, 4–6-week-old female mice infected with the RH strain of T. gondii were treated with different doses (16, 32, 64, 256, and 512 mg/kg) of the fraction using gavage. Results: The highest and lowest lethality of the tachyzoites were 89.6% and 25.9% related to the concentrations of 512 µg/ml and 1 µg/ml, respectively, with an IC50 value of 18.1 µg/ml ± 0.37. The cytotoxicity test showed an IC50 value of 984.3 µg/ml ± 0.76 after 48 h incubation. The mean survival of mice at the lowest treated dose (16 mg/kg) was 6.6 days, and it was 15 days at the highest dose (512 mg/kg). The concentrations of 512, 256, 128, and 64 mg/kg of the fraction compared to the negative control (6.2 days mean survival) significantly increased the survival time of mice (P < 0.001, P = 0.009, P = 0.018, and P = 0.021, respectively). Conclusion: The results showed that the arbutin-rich fraction of P. boissieriana is effective against T. gondii In Vitro and In Vivo and may be a reliable alternative to conventional treatment for toxoplasmosis, although further studies are necessary. [ABSTRACT FROM AUTHOR]

Cold plasma is an emerging non-thermal processing technology that could fulfill the food industry's need for decontamination purposes without compromising the quality if optimized in terms of plasma parameters, including feed gases, voltage, and exposure time. Different food matrices require specialized optimized processes due to the interactions between plasma and the food. In the present study, the response surface methodology was applied to optimize the radiofrequency low-pressure cold plasma processing of saffron (Crocus sativus L. stigmas.) with the aim of achieving the highest decontamination level with the least harm to metabolites. The effects of the treatment time, power, and three gas mixtures (X, Y, and Z) consisting of air, oxygen, and argon on 22 responses related to microbial load and quality of saffron were evaluated in 42 experiments. Eleven critical responses that determine the final quality of saffron were considered to calculate the desirable function as a comprehensive approach for optimization. Analyses showed that all factors significantly affected the desirable function, and the fitted linear model was significant. The optimal condition was determined as an RF power of 76 W for 26 min using the "Y" gas mixture, which reduced the total microorganisms, coliforms, Escherichia coli, molds, and yeast by 5.75, 6.71, 6.07, and 4.00 log CFU g−1 respectively. The optimal condition preserved saffron quality within category I of the ISO specification No. 3632-1. The experimental values were in accordance with the predicted values. Optical emission spectroscopy revealed that the main plasma reactive species were Ar+ species, monoatomic oxygen, O2+, O+ ions, excited N2 species, and N2+ ions. The temperature of the samples after treatment was in the range of 40–44 °C. Scanning electron microscopy of the saffron threads indicated surface etching. Our findings showed that saffron was disinfected without substantial harm to its appearance and metabolites by applying appropriate plasma treatment. [ABSTRACT FROM AUTHOR]

Functional lateralization was previously established for various cognitive domains—but not for number processing. Although numbers are considered to be bilaterally represented in the intraparietal sulcus (IPS), there are some indications of different functional roles of the left vs. right IPS in processing number pairs with small vs. large distance, respectively. This raises the question whether number size plays a distinct role in the lateralization within the IPS. In our preregistered study, we applied anodal transcranial direct current stimulation (tDCS) over the left vs. right IPS to investigate the effect of stimulation as compared to sham on small vs. large distance, in both single-digit and two-digit number comparison. We expected that anodal tDCS over the left IPS facilitates number comparison with small distance, while anodal tDCS over the right IPS facilitates number comparison with large distance. Results indicated no effect of stimulation; however, exploratory analyses revealed that tDCS over the right IPS slowed down single-digit number processing after controlling for the training effect. In conclusion, number magnitude processing might be bilaterally represented in the IPS, however, our exploratory analyses emphasise the need for further investigation on functional lateralization of number processing. [ABSTRACT FROM AUTHOR]

In 2017, blowouts and then explosions occurred in a Middle Eastern oilfield. A root cause of the incident is lack of study and investigation of the past kicks and blowouts data. Therefore, as a pioneer work in the region, data gathering and analysis of past kicks and blowouts were made in the studied oilfield to learn lessons and find gaps. Out of the 149 drilled wells, a total of 117 kicks and three (3) blowouts occurred. In this work, a list of drilling parameters to be considered in data gathering and analysis were suggested as a guideline for future works elsewhere. The statistical analysis not only showed all the three exploration wells kicked which is not a surprise, but it also showed that 39 out of 146 (26.71%) also experienced kicks during reservoir drilling. The large number of kicks in development wells proved that possibility of kick occurrence in development wells is not low. In exploration wells, the predominant kick causes were gas-cut mud and insufficient mud weight which indicates the necessity of using pressure while drilling in addition to drilling rate control systems in exploration wells. However, in development wells, lost circulation was the predominant kick cause indicating the necessity of using low-weight drilling fluids and managed pressure drilling systems. The direct role of human error exists at least in 60% of kicks occurred in this field, which shows the great importance of improved drilling personnel training. Although only 3.45% kicks in development wells occurred due to improper hole fill-up during tripping, this cause should not only be deemed trivial, but it should also be taken seriously as being the cause of the blowout. The 2.56% possibility of kick conversion to blowouts and 67% risk of blowout conversion to explosion emphasize the necessity of maintaining primary well control and using efficient and early kick detection systems. Bullhead was the more commonly used method than standard well control methods; as this kill method may not always be safe, its application should be revised. [ABSTRACT FROM AUTHOR]

Purpose: The proper application of high-quality clinical practice guidelines improves trauma patients' care and outcomes. This study aimed to adopt and adapt guidelines on the timing of decompressive surgery in acute spinal cord injury (SCI) in Iranian clinical settings. Methods: This study followed a systematic search and review of the literature to enter them into the selection process. The source guidelines' clinical suggestions were converted into clinical scenarios for clinical questions on the timing of decompressive surgery. After summarizing the scenarios, we prepared an initial list of recommendations based on the status of the Iranian patients and the health system. The ultimate conclusion was reached with the help of a national interdisciplinary expert panel comprising 20 experts throughout the country. Results: A total of 408 records were identified. After title and abstract screening, 401 records were excluded, and the full texts of the remaining seven records were reviewed. Based on our screening process, only one guideline included recommendations on the topic of interest. All of the recommendations were accepted by the expert panel with slight changes due to resource availability in Iran. The final two recommendations were the consideration of early surgery (≤24 h) as a treatment option in adult patients with traumatic central cord syndrome and in adult patients with acute SCI regardless of the level of injury. Conclusion: Considering early surgery for adult patients with acute traumatic SCI regardless of the level of injury was the final recommendation for Iran. Although most of the recommendations are adoptable in developing countries, issues with infrastructure and availability of resources are the limitations. [ABSTRACT FROM AUTHOR]

Considerable evidence points to a dominant role of inflammation in tumor pathology. The biological response of the immune system can be triggered by Toxoplasma gondii as a common brain-tropic parasite. The aim of this study was to investigate an association between Toxoplasma infection and brain tumors. This case-control study was performed on sera of brain tumor patients (n = 124) and age- and sex-matched control subjects (n = 124) in Southern Iran. Data related to tumor site and type were collected during sample collection. Anti-Toxoplasma IgG was assessed by enzyme-linked immunosorbent assay (ELISA). Seroprevalence anti-Toxoplasma IgG was significantly higher in brain tumor patients 30.6% (38/124) compared with 12.1% (15/124) of the healthy controls (OR 3.211; 95% CI 1.658 to 6.219; p = 0.001). The highest seroprevalence was detected in patients with ependymoma (100%), followed by glioblastoma (83%), pituitary adenoma (47.3%), astrocytoma (27.2%), schwannoma (23%), and meningioma (22.6%). The parasite infection was correlated to brain tumor's location i.e., the patients with frontal lobe and sella region tumors had higher seropositivity compared with others (P < 0.05). The higher prevalence of Toxoplasma infection among patients with brain tumor compared with the control group indicates a probable association between the infection and brain tumors. [ABSTRACT FROM AUTHOR]

Introduction: Thyroid carcinoma is the most common endocrine cancer which may manifest with unusual presentations. We addressed distant metastases as the first presentations of thyroid carcinoma in several patients, though previously considered to occur rarely. Methods: In this case series, 10 patients are introduced with signs and symptoms of distant metastasis. Detailed history, physical examination, laboratory data, and histopathologic final report of thyroid cancer are presented. Conclusion: Although it seems unusual to discover a distant metastasis without abnormal thyroid examination, several reports of similar findings urge the need to improve screening process. It is prudent to bear in mind these presentations for early detection of thyroid carcinoma. [ABSTRACT FROM AUTHOR]

Exposure to PM2.5 can cause various diseases, including allergies, cardiovascular disease, and other related diseases. Therefore, in this study, the level of PM2.5 and potentially toxic elements (PTEs), including nickel (Ni), lead (Pb), chromium (Cr), arsenic (As), and cadmium (Cd), bound to PM2.5 in the indoor air of school were meta-analyzed. PubMed and Scopus were used to retrieve articles on the level of PM2.5 and PTEs in PM2.5 from 1 January 2000 to 20 July 2020. The level of PM2.5 and PTEs in PM2.5 was meta-analyzed based on the country subgroup in the random effect model. Seventy-six articles with 133 data reports were included in our study. Most people spend between 80 and 90 percent of their time indoors. The lowest and highest level of PM2.5 in the indoor air is in Greece (1.71 ug/m3) and Canada (313.39 ug/m3), respectively. The overall pooled level of PM2.5 was 16.29, 95%CI (14.37–18.22 ug/m3). The pooled level of PM2.5 in Canada, Poland, South Korea, Turkey, China, Qatar, India, Serbia, the UK, Taiwan, Iran, Kuwait, Spain, and Portugal was higher than the WHO guideline (25 ug/m3 24-h mean). The rank of PTEs in PM2.5 based on the overall level in the indoor air of urban schools was Ni (7.58 ng/m3) > Pb (6.52 ng/m3) > Cr (3.48 ng/m3) > As (1.61 ng/m3) > Cd (0.74 ng/m3). All counties' pooled Ni and Cr in PM2.5 were higher than standard limits. Therefore, it is recommended to carry out control programs to reduce the emission of air pollutants around schools. [ABSTRACT FROM AUTHOR]

Heat transfer in cavities under the influence of magnetic field is very important in industry. The effect of the presence of a magnetic field on the behavior of heat transfer in closed cavities (electrical transformers) is inevitable, which is addressed in this research. The present study is about the heat transfer of water/alumina nanofluid in a rectangular cavity. The cavity has two insulated walls in front of each other, a constant temperature warm wall at an angle of zero with the horizontal and a constant temperature cold wall. A constant magnetic force with Hartmann number of Ha = 0–45 is applied, which has a zero angle with respect to the horizontal line. The Rayleigh number is Ra = 105, and the problem is solved for various length-to-width cavity aspect ratios of AR = 1–6. In this paper, the solution method uses a finite volume discretization with a pressure-based and segregated algorithm. Results revealed that for AR = 1, the temperature contours have a decreasing trend from top to bottom, as it experiences the maximum and minimum temperatures near the warm and cold walls. For this aspect ratio, the minimum dimensionless temperature occurs at the dimensionless position of X = 0.7–0.8 for various Hartmann numbers, which also coincides with the maximum Nusselt number. For the aspect ratio of AR = 2, increasing the magnetic force results in a higher Lorentz force, which opposes the buoyancy force, reducing the local Nusselt number. However, for AR = 4, increasing the magnetic force creates straight isothermal lines. For this aspect ratio, the isothermal lines are close to each other near the warm wall at two points of X = 0.3 and 0.7, with a slight temperature difference, thereby maximizing the Nusselt number. For AR = 6 and all Hartmann numbers, the Nusselt number is maximum at two points of X = 0.34 and 0.65, while the minimum is located at X = 0.2, 0.5, and 0.8. [ABSTRACT FROM AUTHOR]

This study specifically investigates the impact of economic policy uncertainty (EPU) on travel and leisure (TL) companies' debt holdings policy. To the best of our knowledge, there is a momentous gap in exclusively conducting the impact of EPU on the debt holdings policy behavior of Western European firms operating in the TL sector and its sub-sectors, namely the airlines, gambling, hotels, recreational services, restaurants and bars, and travel and tourism. In this sector, external financing is strongly needed to finance enormous investments and replace, expand, and modernize tangible and intangible assets. To fill the gap, the present study selects 92 publicly listed TL companies operating in Western Europe's top tourist destinations, namely, the UK, Germany, France, Spain, and Italy, and performs both the static and dynamic panel data estimation approaches during the 2005–2019 period. The results reveal that the EPU negatively impacts TL firms' debt holdings, implying that firms tend to decline in debt levels by rising EPU. Consequently, the results highlight that the level of EPU matters, and firms' debt ratios are relatively lower in countries having a higher EPU and vice versa. Besides, the results underscore that the EPU negatively impacts firms' debt holdings in each sub-sector; however, the negative effect is most prominent on the debt ratios of the firms, particularly those operating in gambling, hotels, travel, and tourism, and also recreational services sub-sectors. The results are robust and have important suggestions for regulatory bodies, policymakers, and firms' managers. [ABSTRACT FROM AUTHOR]

Introduction: Cystic echinococcosis (CE) is a neglected tropical disease caused by the larval stages of Echinococcus granulosus (E. granulosus). MicroRNAs (miRNAs) are small noncoding RNAs acting as mediators in host-parasite interaction. Recently, numerous studies have been conducted on miRNAs in infectious diseases; however, little data are available about the role of miRNAs in pathogenesis and early diagnosis of CE. Methods: The current study evaluated the expression of four E. granulosus-derived miRNAs, including egr-miR-125,5p, egr-let-7,5p, egr-miR-2, and egr-miR-71 in fibrotic and healthy liver tissues of 31 CE patients with active and inactive hydatid cysts by qRT-PCR. Results: Of the 31 patients, 48.4% had active cysts (CE1 and CE2), while the remainder had transitional (16.1%) and inactive (35.5%) CE types cysts. The qRT-PCR analysis revealed a significant increase of 11.2, 9.91, 6.2, and 13.1-fold in the fibrotic tissue group for egr-miR-125,5p, egr-let-7,5p, egr-miR-2, and egr-miR-71, respectively. Among these miRNAs, egr-miR-125-5p exhibited the highest area under the curve (AUC) value of 0.8050 for predicting liver fibrosis. Conclusions: Our findings provide new data about the role of E. granulosus-derived miRNAs in pathogenesis of CE. The high AUC of egr-miR125,5p reflecting the possibility of using egr-miR125,5p as biomarker in CE diagnosis. Further studies on serum of CE patients are needed to confirm the potential role of circulating egr-miR-2a-3p and egr-miR-125-5p in the early diagnosis of CE. [ABSTRACT FROM AUTHOR]

Introduction: Cystic Echinococcosis (CE) is a chronic parasitic disease caused by the metacestodes of Echinococcus granulosus senso lato (E. granulosus s.l.). The larval stages of this parasite, hydatid cyst, are usually diagnosed using imaging modalities and serological testing; however, several studies have recently suggested using the parasite-derived microRNAs (miRNAs) as novel diagnostic biomarkers. Materials and Methods: The present study included 31 CE patients who were older than 5 years and were admitted to the hospitals of Ahvaz, Iran for hydatid cyst removal surgery during 2019–2021. The egr-miR-125-5p and egr-miR-2a-3p levels were evaluated in the sera of the CE patients before and 6 months after the surgery using Quantitative Real-Time PCR (qRT-PCR), and the results were compared with the serum samples from 15 healthy volunteers. Then, the intergroup comparisons were performed using the t test. Results: The patients' age range was 6–72 years, with a mean age of 34.6 years. Moreover, based on the classification by the WHO-IWGE, one patient (3.2%) had CE1, 14 patients (45.2%) had CE2, 5 patients (16.1%) had CE3, 2 patients (6.5%) had CE4, and 9 patients (29%) had CE5. Also, 21 patients (67.74%) had a positive antigen test using the ELISA method, while 10 patients (32.26%) had a negative ELISA. The pre-operative expression level of egr-miR-2a-3p was 10.36 folds higher compared to 6 months after the surgery, with an AUC value of 0.8176. However, the expression levels of egr-miR-125-5p did not change significantly 6 months after the surgery compared to pre-operative levels. Conclusions: According to the present study results, the serum levels of egr-miR-2a-3p can be a promising non-invasive biomarker for diagnosing CE and monitoring its potential recurrence after cystectomy. [ABSTRACT FROM AUTHOR]

Despite community vaccination against coronavirus disease 2019 (COVID-19) and reduced mortality, there are still challenges in treatment options for the disease. Due to the continuous mutation of SARS-CoV-2 virus and the emergence of new strains, diversity in the use of existing antiviral drugs to combat the epidemic has become a crucial therapeutic chance. As a broad-spectrum antiparasitic and antiviral drug, ivermectin has traditionally been used to treat many types of disease, including DNA and RNA viral infections. Even so, based on currently available data, it is still controversial that ivermectin can be used as one of the effective antiviral agents to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or not. The aim of this study was to provide comprehensive information on ivermectin, including its safety and efficacy, as well as its adverse effects in the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

Exposure to potentially toxic elements (PTEs) bound to PM2.5 can cause various health effects, including cardiovascular disease, allergies, and other related diseases. There have been several studies on the concentration of PTEs, including zinc (Zn), iron (Fe), and manganese (Mn) bound PM2.5 in the indoor air of urban schools. In this study, the concentration of Zn, Fe, and Mn in the indoor air of schools bound PM2.5 were meta-analyzed. PubMed and Scopus were used to retrieve papers related to the concentration of PTEs bound PM2.5 in the indoor air of urban schools from January 1, 2000 to March 10, 2020. The concentration of PTEs in PM2.5 was meta-analyzed based on the country subgroup in the random-effects model (REM). Thirty papers with 25 data reports were included in the study. The rank order of PTEs bound PM2.5 was Zn (17.32 ng/m3) > Fe (14.49 ng/m3) > Mn (7.40 ng/m3). The rank order of countries based on the concentration of Fe-bound PM2.5 in the indoor air of urban schools was China > Poland > Italy > Spain > Taiwan > Turkey > Iran) > Chile; Zn, Poland > Iran > Taiwan > Turkey > Spain > Italy > Chile; and for Mn, Poland > China > Iran > Taiwan > Spain > Italy > Chile. The pooled concentration of PTEs (Fe, Mn, and Zn) bound PM2.5 in the indoor air of urban schools in Poland and China was higher than in other countries, hence, therefore, it is recommended to carry out a PM2.5 concentration reduction program in the indoor air of schools in these countries. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis (CL) is one of the most important parasitic diseases in the world. Despite the existence of many therapeutic strategies, the treatment of this infection still faces problems. Sodium chlorite as an antimicrobial agent has been shown to have acceptable tissue regenerative and wound healing properties. Therefore, the present study aimed to analyze the in vitro effects of different concentrations of sodium chlorite on Leishmania major promastigotes and macrophage cells. The inhibitory and toxicity effect of various concentrations (0.0035, − 1.8 mg/ml) of sodium chlorite on the standard Iranian strain of L. major promastigotes were evaluated via counting the cells and flow cytometry. Furthermore, cytotoxicity on promastigotes and J774 macrophage cell line were performed by MTT assay. The results of the inhibitory test demonstrated that sodium chlorite had dose-dependent, anti-leishmanial activities. The half-maximal inhibitory concentration (IC50) for promastigotes and J774 cells by cytotoxicity test was detected at 0.17 mg/ml and 0.08 mg/ml after 48 h respectively. Flow cytometry results showed that 27.34% death of promastigotes was observed in 0.0035 mg/ml of sodium chlorite and 78.12% in 1.8 mg/ml. The results of the present study showed that sodium chlorite could be used as an effective treatment for CL, especially in cases resistant to treatment with pentavalent compounds. However, the toxicity of this substance in high concentrations should be considered in clinical setting. [ABSTRACT FROM AUTHOR]

The flow shop scheduling problem is one of the most complex and widely applicable scheduling problem. In this paper, we design efficient parallel algorithms for solving large-size non-permutation flow shop scheduling problems by leveraging the huge amount of computing power of the current multi-core computing systems. We design two parallel algorithms based on the Shifting Bottleneck heuristic. The first one is a coarse-grained parallel algorithm that is suitable for execution on multi-core systems with a small number of cores, while the second one is a fine-grained parallel algorithm suitable for multi-core systems with a large number of cores. We perform an extensive experimental analysis to evaluate the performance of the proposed algorithms for instances of various sizes. The results show that the proposed algorithms can solve large-size instances of the problem in a reasonable amount of time and obtain solutions that are within acceptable distance from the lower bounds. The proposed parallel algorithms achieve good speedup with respect to the serial variants of the algorithms. [ABSTRACT FROM AUTHOR]

Introduction: The main mechanism underlying hepatic fibrosis is the imbalance between tissue Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinases (TIMPs). This study aimed to investigate the potential role of TIMP-1 and TIMP-2 in the process of hepatic fibrosis caused by Echinococcus granulosus senso lato (E. granulosus s.l.). Methods: The expressions levels of TIMP-1 and TIMP-2 mRNAs were evaluated in fibrotic and normal hepatic tissues of 30 patients with Cystic Echinococcus (CE) using qRT-PCR. Moreover, their serum levels of TIMP-1 were assessed before CE cyst removal and 6 months after surgery using ELISA. Results: The qRT-PCR results showed that the expression levels of TIMP-1 and TIMP-2 mRNAs were significantly higher in the fibrotic hepatic tissue compared to the normal liver tissue, in a way that the TIMP-1 and TIMP-2 mRNA expression levels were 19.07 and 6.58 folds higher in the fibrotic tissue compared to the normal liver tissue. Among these TIMPs, TIMP-1 exhibited the higher area under the curve (AUC) value for predicting liver fibrosis. However, we could not find a significant difference in the serum levels of TIMP-1 before and after the cyst removal procedure (p = 0.48). Conclusions: For the first time, our study showed that the significant overexpression of both TIMP mRNAs in the fibrotic liver tissue of the CE patients may be due to the increased expression of MMPs in the peri-cystic tissue. However, we could not find a significant difference in the pre- and post-operative TIMP-1 levels, which may be due to recurrence or heterogeneity in the cyst type. Therefore, performing further studies with a larger sample size of the CE patients is recommended. [ABSTRACT FROM AUTHOR]

Nanotechnology is a developing and revolutionary science that has been widely recommended for diagnosis and treatment of cancer. Among the various nanoparticles used in nanotechnology, gold nanoparticles (AuNPs) have attracted much attentions due to their promising anticancer properties. Despite the potential advantages of AuNPs, their apoptotic and anti-angiogenic effects have not yet been reported on human bladder cancer 5637 cells. This motivated us to evaluate (reactive oxygen species) ROS-mediated apoptosis in 5637 cells. For this task, inhibitory effect of AuNPs was investigated after 24-h exposure to different concentrations of AuNPs by MTT assay. Also, apoptosis level was assessed by ROS production, flow cytometry, and Hoechst 33,258 staining. Besides, mRNA expression of B-cell lymphoma protein 2 (Bcl-2), Bcl-2-associated X (Bax), vascular endothelial growth factor A (VEGFA) genes, and caspase-3,7 activity were determined by qRT-PCR and colorimetric assay, respectively. Moreover, migration rate was evaluated by wound healing assay. MTT results demonstrate that AuNPs can reduce 5637-cell viability in a dose-dependent manner, while fluorimetric assay data show significant increased ROS production in 25 and 50 µg/ml-treated cells. It is also observed that AuNPs lead to Bax overexpression and downregulation of Bcl-2 and VEGFA genes. In line with this, flow cytometry results show increased levels of apoptosis in 25 and 50 µg/ml AuNP-treated cells (p < 0.05). Similarly, Hoechst staining indicates a remarkable increase in cells with apoptotic morphology after treating with AuNPs. Overall, our findings show that AuNPs significantly provoke ROS production, induce apoptosis, and suppress cell migration in bladder cancer 5637 cells. [ABSTRACT FROM AUTHOR]

Toxoplasmosis is a globally parasitic zoonotic disease transmitted by Toxoplasma gondii protozoa. This infection in its chronic form can cause a change in its host's specific behavior and is also associated with developing neuropsychological symptoms in humans. Changes in neurotransmitters' levels, especially dopamine, have been identified as a behavior change factor in the infected host. This study aimed to evaluate serum dopamine levels in acute murine toxoplasmosis. In this study, 50 mice infected with Toxoplasma were studied in 5 separate groups, and ten healthy mice were considered as negative control. For five consecutive days after parasite injection, blood sampling and serum isolation were performed daily from one of the groups. Serum dopamine levels were measured by HPLC method. Statistical studies showed that serum dopamine on the first to the fourth day after parasite inoculation was the same as the negative control, but the fifth day began to increase. The present study results indicate that dopamine production in mice infected with Toxoplasma gondii increases from day five after infection. This result suggests that in acute toxoplasmosis, dopamine production is low, and the trend of chronic disease increases dopamine production. [ABSTRACT FROM AUTHOR]

Of the most common infectious diseases that occur mainly by uropathogenic Escherichia coli (UPEC) is urinary tract infections (UTIs). The purpose of this study was to investigate virulence factors, antibiotic resistance, and phylogenetic groups among UPEC strains isolated from patients with UTI in southern Iraq. A total of 100 UPEC isolates were collected from urine samples of UTI patients from various hospitals in southern Iraq, and confirmed by morphological and biochemical tests. Antimicrobial susceptibility testing on isolates was performed by disk diffusion method. Multiplex PCR techniques were used to evaluate the phylogenetic groups based on Clermont method and to detect the presence of six virulence factor genes. The majority of isolates belonged to the phylogenetic groups B2 (46%) and C (13%). The most prevalent virulence factors were fimH (96%), followed by aer (47%), papC (36%), cnf1 (17%), hly (15%), and afa (8%). Phenotypic testing showed that the isolates were most resistant to piperacillin, ticarcillin, amoxicillin/clavulanic acid (92%, 91%, and 88%, respectively) and most sensitive to amikacin and imipenem, respectively. The maximum antibiotic resistance and virulence factors were observed in the phylogenetic group B2. The results showed that the UPEC isolates had all six virulence factors with high frequency and the highest drug resistance. Besides, the results showed a direct relationship between virulence factors, gene diversity, phylogenetic background, and antimicrobial resistance in the UPEC isolates. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) imposes high economic burden to the health systems. However, the risk factors for development of the disease are still remained unknown. Exposure to heavy metals may be associated with occurrence of UC. The aim of this study was to evaluate the relationship between the concentration of metal(loid)s including Pb, As, Ni, Cu, Zn, Fe, and Se in drinking water with incidence of UC. To do this, 35 biopsy samples were each taken from patients and healthy subjects along with the same number of samples of their drinking water. The furnace atomic absorption spectrophotometry was used for sample analysis. Our results showed that exposure to Pb, As, Cu, and Fe was associated with occurrence of UC (ORs > 1; P < 0.05); meanwhile, the concentrations of Zn and Ni were higher in healthy subject biopsies than UC patients (ORs < 1; P < 0.05). Also, the mean concentration of Pb in the drinking water samples (0.12 ± 0.07 mg/L) was higher than the permissible limit of the Institute of Standards and Industrial Research of Iran (ISIRI). The results showed that by increasing Pb in drinking water, Zn concentration in the intestinal tissues of patients was decreased (P = 0.005). However, the concentration of Pb, As, Cu, and Fe in UC patients may affect the exacerbation of the disease, though Zn may potentially reduce the risk of this disease. In conclusion, our findings demonstrated that exposure to the metal ions through drinking water can affect the body's heavy metal content, which may be act as preventing or developing factors for UC. [ABSTRACT FROM AUTHOR]

Estrogen receptor alpha (ER/ESR1) is frequently mutated in endocrine resistant ER-positive (ER+) breast cancer and linked to ligand-independent growth and metastasis. Despite the distinct clinical features of ESR1 mutations, their role in intrinsic subtype switching remains largely unknown. Here we find that ESR1 mutant cells and clinical samples show a significant enrichment of basal subtype markers, and six basal cytokeratins (BCKs) are the most enriched genes. Induction of BCKs is independent of ER binding and instead associated with chromatin reprogramming centered around a progesterone receptor-orchestrated insulated neighborhood. BCK-high ER+ primary breast tumors exhibit a number of enriched immune pathways, shared with ESR1 mutant tumors. S100A8 and S100A9 are among the most induced immune mediators and involve in tumor-stroma paracrine crosstalk inferred by single-cell RNA-seq from metastatic tumors. Collectively, these observations demonstrate that ESR1 mutant tumors gain basal features associated with increased immune activation, encouraging additional studies of immune therapeutic vulnerabilities. Mutations of ESR1, the gene encoding the estrogen receptor alpha, are associated with acquired resistance to therapy in luminalbreast cancer. Here the authors show that ESR1 mutant tumors gain basal-like features with increased expression of basal cytokeratines and immune activation. [ABSTRACT FROM AUTHOR]

In this paper, the microbial degradation of methyl red (MR) was investigated by novel isolated bacteria S1 and K1 from wastewater effluent. Based on morphological, biochemical and molecular methods, strain S1 belonged to the Staphylococcus schleiferi subsp. coagulans GA 211 with 92.67% similarity (accession number MT573965) and strain K1 belonged to the Klebsiella michiganensis W14 with 99.85% similarity (accession number MT572941). To the best of our knowledge, this is the first report of dye degradation activity of these bacteria. The Taguchi Statistical Method (TSM) was used to optimize the experimental conditions. Taguchi's L18 orthogonal array (OA) was performed, and the results were used to calculate signal-to-noise (S/N) ratios. According to S/N ratios, it was discovered that optimum experimental conditions are at pH 8, temperature 40°C, initial dye concentration 50 mg/l, carbon source glucose, rpm 75, inoculum 3% v/v and strain S1. Analyzing the results of the biodegradation assay by Minitab 19 statistical software, it was found that rpm and temperature are most and less effective in the MR biodegradation assay, respectively. Significant changes in the HPLC and UV-Vis spectrum of samples of strain S1 before and after biodegradation assay confirmed the complete biodegradation of MR by S1 strain. [ABSTRACT FROM AUTHOR]

Recent evidence reveals that miRNA sponges neutralize miRNAs activity by binding to miRNAs and sequester them from their relevant targets to regulate expression. The detailed mechanisms of sponge RNAs in colorectal cancer remain to be exactly determined. In this study DANCR, miR-145-5p, NRAS axis was evaluated and the diagnostic value of these targets was assessed in colorectal cancer patients. A case-control study was carried out on 40 samples of tumor tissues and 40 adjacent tissues. Total RNA was extracted, and then, the expression level of DANCR, miR-145-5p and NRAS was evaluated using qRT-PCR. In addition, the sensitivity and specificity of these markers were evaluated by receiver operating characteristic (ROC) curve analysis. Our results revealed that the expression level of DANCR was significantly upregulated in colorectal cancer tissues (p < 0.001). It was demonstrated that DANCR could regulate NRAS expression by sponging miR-145-5 in colorectal cancer patients. Furthermore, the mean expression of miR-145-5p (p < 0.001) and NRAS (p < 0.001) was significantly different between tumor and normal tissue. A significant correlation was observed between DANCR and miR-145-5p (p = 0.001), and also between miR-145-5p and NRAS (p < 0.001). Sensitivity and specificity value for DANCR, miR-145-5p and NRAS were (0.875 and 0.725), (0.875 and 0.745), and (0.877 and 0.694), respectively. According to the values of sensitivities and specificity of DANCR, miR-145-5p and NRAS, confirmed with ROC curve analysis, these biomarkers may be useful in the screening and differentiating between tumor and control sample in colorectal neoplasm. [ABSTRACT FROM AUTHOR]

The honey bee, Apis mellifera L., is the world's most important managed pollinator of agricultural crops, however, Varroa mite, Varroa destructor Anderson and Trueman, infestation has threatened honey bee survivorship. Low efficacy and development of Varroa mite resistance to currently used Varroacides has increased the demand for innovative, effective treatment tool options that exhibit high efficacy, while minimizing adverse effects on honey bee fitness. In this investigation, the toxicity of 16 active ingredients and 9 formulated products of registered miticides for use on crops from 12 chemical families were evaluated in comparison to amitraz on Varroa mites and honey bees using contact surface and topical exposures. It was found that fenpyroximate (93% mortality), spirotetramat (84% mortality) and spirodiclofen (70% mortality) had greater toxicity to Varroa mites, but high dose rates caused high bee mortality (> 60%). With this in mind, further research is needed to investigate other options to minimize the adverse effect of these compounds on bees. The results also found high toxicity of fenazaquin and etoxazole against Varroa mites causing 92% and 69% mortality, respectively; and were found to be safe on honey bees. Collectively, it is recommended that fenazaquin and etoxazole are candidates for a potential Varroacide and recommended for further testing against Varroa mites at the colony level. [ABSTRACT FROM AUTHOR]

The most important pathogenesis factor in the Apicomplexa parasites is invasion to the host cell. Given the inhibitory role of Butanedione Monoxime (BDM) on myosin–actin interaction, this study aimed to investigate the effects of this molecule on the vitality and infectivity of Toxoplasma tachyzoites in order to provide a new option for vaccine development. The tachyzoites of the RH strain of Toxoplasma gondii were exposed to different concentrations (1, 2, 4, 8, 16, 32, 64, and 128 μg/mL) of BDM, and mortality effect was assessed by flow cytometry. Then, the penetration ability of the tachyzoites was investigated in HeLa and macrophage cell lines. The infectivity of exposed tachyzoites to BDM were also investigated in mice through following up and detecting the etiological factor. The highest percentage of mortality (72.69%) was seen in the tachyzoites exposed to 128 μg/mL of the compound. The tachyzoites exposed to 32, 64, and 128 μg/mL of BDM began the proliferation in HeLa cells after 48 h, while this proliferation was initiated within 24 h in macrophage cells. All the mice inoculated with the BDM-treated tachyzoites died after 13 days. The mean survival time of the mice receiving tachyzoites exposed to 128 μg/mL of BDM was 12.4 days, which was significantly different from the negative control group (p = 0.001). BDM, as the inhibitor of myosin–actin interaction, and other substances that block the entry of parasites into cells may be suitable candidates for vaccine production against Toxoplasma. Yet, future studies are required to be conducted on the issue. [ABSTRACT FROM AUTHOR]

A new keratinase producer, Bacillus sp. BK111, isolated from a poultry feather was identified as Bacillus zhangzhouensis, which is the first report for its keratinolytic activity. The keratinase production was optimized, followed by the enzyme purification and characterization using biochemical assays. A 2.34-fold increase was observed in the enzyme production under optimized conditions. The enzyme was characterized as a serine protease with 42 kDa molecular weight, stable in a wide range of temperature and pH with maximum keratinolytic activity at 60 °C and pH 9.5. The enzyme had a wide range of different substrates with the best performance on the feather meal substrate. Metal ions of Ca2+, K+, Na+ and Mn2+ enhanced the enzyme activity. The enzyme showed a great deal of stability in the presence of ethanol, methanol, acetone, 2-propanol, dimethyl sulfoxide, Tween-80 and Triton X-100. Dithiothreitol (DTT), as a reducing agent, caused a twofold increase in keratinolytic activity. The half-life of the enzyme at optimum temperature was calculated to be 125 min and the ratio of keratinolytic:caseinolytic for the enzyme was 0.8. Our results showed the remarkable features of the enzyme that make it suitable for biotechnological usages. [ABSTRACT FROM AUTHOR]

Acinetobacter species are defined as multidrug-resistant pathogens and the development of resistance against antimicrobials is a major problem in the treatment of infections caused by them. This study aimed to evaluate the antibacterial activity of aqueous and methanol extracts of Salvia chorassanica and Artemisia khorassanica on multidrug-resistant Acinetobacter isolates and also examining the interaction of the methanol extract of the plants with the combination of amikacin and imipenem. First, the presence of adeI and adeB genes in bacterial isolates was investigated. The aqueous and methanol extracts of the leaves of the plants were prepared by ‏Maceration method. Minimum Inhibition Concentration (MIC) values were determined to evaluate the antibacterial activities of plant extracts and antibiotics. Combined effects of the antibiotics with plant extracts were performed using the checkerboard method. The accumulation assay was used to examine the inhibitory effects of plant extracts on the bacterial efflux pump. MIC results indicated that the methanol extracts were effective against Acinetobacter species. FICI values indicated that the combination of antibiotics with methanol plant extracts improves bacterial sensitivity to antibiotics. The extracts also exhibited efflux pump inhibitory activities. Consequently, combination of the plant extracts with antibiotics could enhance the antibiotic susceptibility of resistant pathogens. [ABSTRACT FROM AUTHOR]

Background: Ultrasonography is a suitable modality that can potentially improve patient care, saving time and lives. Purpose: This article has evaluated the caveats and pitfalls of point-of-care ultrasonography in the diagnosis of pneumothorax, hemothorax and contusion. Materials and methods: This prospective study was performed in 157 patients with blunt chest trauma in 3 university hospitals. Ultrasonography was performed by 2 board-certified emergency medicine specialists and an emergency medicine resident PGY-3 after passing the training process successfully. Results: The false-negative cases were not significantly correlated with accompanying traumatic injuries. Lung ultrasonography accompanied by chest physical examination show accuracy 91.8. Point-of-care ultrasonography (PoCUS) showed sensitivity 75.0%, specificity 100%, positive-predictive value (PPV) of 100% and a negative-predictive value (NPV) of 94.9% for the diagnosis of pneumothorax. For hemothorax, bedside PoCUS had a sensitivity of 45.4%, specificity of 100%, PPV of 100% and NPV of 91.8%. PoCUS was assessed 58.1% sensitive and 100% specific for detecting lung contusion with positive-predictive value (PPV) of 100% and a negative-predictive value (NPV) of 86.3%. Performing US resulted in no false-positive cases. Conclusions: Point-of-care ultrasonography was highly sensitive to detect pneumothorax and can be beneficial for the disposition of stable patients and to detect PTX in unstable patients before transferring to the operating room. It is also moderately appropriate for the diagnosis of hemothorax and lung contusion compared to the gold standard, CT scan. It is essential to consider the false-negative and false-positive instances of lung ultrasound in various situations to enhance management and disposition of blunt thoracic injuries. [ABSTRACT FROM AUTHOR]

Liver fibrosis is a dynamic process that occurs in response to chronic liver disease resulting from factors such as chronic infections, autoimmune reactions, allergic responses, toxins, radiation, and infectious agents. Among the infectious agents, multicellular parasites cause chronic inflammation and fibrosis. Twenty-five patients with different stages of cystic echinococcosis (CE) were enrolled in the study. The expression of ACTA2, COL3A1, IFN-γ, MMP2, MMP9, TGF-β1, and TNF-α genes was determined by qRT-PCR in healthy and fibrotic liver tissue of the CE patients. TGF-β1 expression was evaluated by immunohistochemistry, and histology was conducted to assess the development of liver fibrosis. Expression of MMP9, ACTA2, COL3A1, and MMP2 was found significantly higher in the fibrotic tissue compared to healthy tissue. We observed a significant correlation between TGF-β1 and TNF-α gene expressions and liver fibrosis. The mRNA level of IFN-γ was lower in the fibrotic than in the healthy hepatic tissue. Immunohistochemistry analysis revealed TGF-β1 upregulation in the fibrotic tissue. Histology showed inflammation and fibrosis to be significantly higher in the fibrotic tissue. The findings of this study suggest that Echinococcus granulosussensu lato can promotes fibrosis through the overexpression of TGF-β1, MMP9, ACTA2, COL3A1, and MMP2. The downregulation of IFN-γ mRNA in fibrotic samples is probably due to the increased production of TGF-β1 and the suppression of potential anti-fibrotic role of IFN-γ during advanced liver injury caused by E. granulosussensu lato. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the association between rs13266634 polymorphism in SLC30A8 gene and type 2 diabetes in Iranian population, and also to provide a way for adjusting the deviation from the Hardy-Weinberg equilibrium. Methods: This was a case-control study, the patients were selected from the East Azerbaijan province, Iran. In this study, 125 patients with type 2 diabetes (cases) and 125 healthy individuals (controls) were studied. Genotype and allele frequencies were determined in both groups, and the deviations from the Hardy-Weinberg equilibrium were assessed using Bayesian analysis. Results: A statistically significant association was observed between rs13266634 polymorphism in SLC30A8 gene and type 2 diabetes. In genotype assessing, data analysis showed that, TT genotype play a role in diabetes type 2 risk (P = 0.001). Subjects with TT genotype had a lower risk of diabetes compared to those with CC and CT genotypes. Also, there was no significant relationship between this polymorphism and type 2 diabetes mellitus in the absence of Hardy-Weinberg equilibrium. Conclusion: Our findings show that, rs13266634 polymorphism was associated with the type 2 diabetes risk in the population of Eastern Azerbaijan province; however, the low number of TT homozygous genotypes affected the precision of the results. Also, the deviation from HWE affected the results. It is recommended to perform further studies to establish Hardy-Weinberg equilibrium. The inconsistency in the results may be due to the ignorance of this equilibrium. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive overview of artificial intelligence (AI) for serious games. Reporting about the work of a European flagship project on serious game technologies, it presents a set of advanced game AI components that enable pedagogical affordances and that can be easily reused across a wide diversity of game engines and game platforms. Serious game AI functionalities include player modelling (real-time facial emotion recognition, automated difficulty adaptation, stealth assessment), natural language processing (sentiment analysis and essay scoring on free texts), and believable non-playing characters (emotional and socio-cultural, non-verbal bodily motion, and lip-synchronised speech), respectively. The reuse of these components enables game developers to develop high quality serious games at reduced costs and in shorter periods of time. All these components are open source software and can be freely downloaded from the newly launched portal at gamecomponents.eu. The components come with detailed installation manuals and tutorial videos. All components have been applied and validated in serious games that were tested with real end-users. [ABSTRACT FROM AUTHOR]

Soluble forms of vascular adhesion molecules, ICAM-1 and VCAM-1, accelerate atherosclerosis pathogenesis. The present study was conducted to evaluate the effect of daily supplementation of 3 g cinnamon on the plasma levels of ICAM-1 and VCAM-1 among patients with type 2 diabetes. This randomized double-blind placebo-controlled trial was performed on 44 adult patients with type 2 diabetes aged 25-70 years. The patients were randomized to two groups of intervention (n = 22) and control (n = 22), differing by daily cinnamon supplementation or placebo (3 g) for 8 weeks. Plasma levels of ICAM-1 and VCAM-1 were measured at the beginning and end of the study. After 8 weeks, 39 subjects (n = 20 in the cinnamon and n = 19 in the placebo groups) completed the trial. There was a significant reduction in the mean levels of ICAM-1 and VCAM-1 within cinnamon and placebo groups (P < 0.001). But there was no significant difference in ICAM-1 (P = 0.75) and VCAM-1 (P = 0.72) between the groups at the end of the trial. According to the results, cinnamon supplementation has no beneficial effect on the reduction of ICAM-1 and VCAM-1 levels in patients with type 2 diabetes, which have a role in the development of atherogenesis. [ABSTRACT FROM AUTHOR]

In the present study, 10,116 body weight-age records were measured on 2537 Kermani lambs. The records were collected from Kermani Sheep Breeding Station, located in Shahrbabak city, Kerman Province, south-eastern part of Iran, between 1993 and 2013 and used for evaluation of non-linear models describing growth curve from birth to yearling age and estimation of genetic parameters for growth curve traits in Kermani sheep. Six non-linear models including Brody, negative exponential, von Bertalanffy, Richards, Verhulst, and Gompertz were compared applying Akaike's information criterion (AIC), root mean square error (RMSE) and Durbin-Watson statistic (DW) for determining the most appropriate model describing the growth curve in Kermani sheep. The von Bertalanffy model showed the lowest AIC and RMSE among the tested models. Furthermore, positive autocorrelations were found between residuals under the all tested model with the lowest value under the von Bertalanffy model. Therefore, von Bertalanffy model was selected as the best one for describing growth curve in Kermani sheep. A multivariate animal model was used for genetic analysis of the growth curve traits including parameters A (estimated mature weight), B (an integration constant related to initial animal weight), K (maturation rate), inflection age (IA), and inflection weight (IW) under a Bayesian approach. Posterior means for heritability estimates of A, B, K, IA, and IW were significant values of 0.10, 0.03, 0.04, 0.15, and 0.10, respectively. The parameter A had significant and positive genetic and phenotypic correlations with parameters B, IA, and IW. The posterior means for genetic and phenotypic correlations between parameters A and K were negative estimates of − 0.32 and − 0.22, respectively, implied that the lambs with slower maturation rate had higher mature weight. Positive and medium estimates were obtained for posterior means of phenotypic (0.31) and genetic (0.35) correlations between B and K. The posterior means for phenotypic and genetic correlations of B with IA and IW were not statistically significant. High and positive estimates were obtained for posterior means of genetic (0.6) and phenotypic (0.84) correlations between IA and IW. Generally, von Bertalanffy model showed high level of adequacy for describing the growth curve in Kermani sheep. Low additive genetic variations were found for all the studied growth curve traits. Therefore, the traits highly influenced by environmental which necessitate improving environmental influencing factors on the studied traits for achieving desired shape of growth curve and developing an efficient breeding strategy in Kermani sheep. [ABSTRACT FROM AUTHOR]

This paper represents our newly developed software for emotion recognition from facial expressions. Besides allowing emotion recognition from image files and recorded video files, it uses webcam data to provide real-time, continuous, and unobtrusive facial emotional expressions. It uses FURIA algorithm for unordered fuzzy rule induction to offer timely and appropriate feedback based on learners' facial expressions. The main objective of this study was first to validate the use of webcam data for a real-time and accurate analysis of facial expressions in e-learning environments. Second, transform these facial expressions to detected emotional states using the FURIA algorithm. We measured the performance of the software with ten participants, provided them with the same computer-based tasks, requested them a hundred times to mimic specific facial expressions, and recorded all sessions on video. We used the recorded video files to feed our newly developed software. We then used two experts' opinions to annotate and rate participants' recorded behaviours and to validate the software's results. The software provides accurate and reliable results with the overall accuracy of 83.2%, which is comparable to the recognition by humans. This study will help to increase the quality of e-learning. [ABSTRACT FROM AUTHOR]

Purpose: Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer that is predominantly estrogen receptor alpha (ER)-positive (+) and is thus treated with endocrine therapies. Herein, we sought to understand the molecular underpinnings of the 4-hydroxytamoxifen (4OHT) resistance in ILC by assessing the potential role of the epithelial-to-mesenchymal transition transcription factor (EMT-TF) SNAIL (SNAI1). Methods: Using a series of breast cancer cell lines, we measured the basal, estrogen and 4OHT-induced expression of SNAIL and other EMT-TF family members by quantitative reverse transcription-polymerase chain reaction and immunoblotting. Chromatin immunoprecipitation experiments were performed to assess ER binding to the SNAIL promoter. Cell proliferation, cell cycle and apoptosis were assessed in 2D cultures. 3D growth was assessed in Matrigel and Collagen I cultures. Results: Estrogen and 4OHT induced SNAIL expression, but not that of the other EMT-TF family members SLUG (SNAI2) and SMUC (SNAI3), with the 4OHT effect being specific to the lobular but not the ductal subtype. We observed estrogen and 4OHT-induced ER recruitment to the SNAI1 promoter and high endogenous basal levels of SNAIL and several EMT-TFs in ILC cell lines. While SNAIL knockdown had a minor impact on the 4OHT partial agonism in estrogen-depleted conditions, it led to a surprising increase in cell proliferation in full serum. In complementary experiments, inducible SNAI1 overexpression caused decreased proliferation, associated with a cell cycle arrest in G0/G1. Additionally, apoptosis was observed in BCK4 cells. Conclusion: These data suggest a previously unrecognized role for SNAIL in ILC, substantiating a context-dependent behavior for this EMT-TF. [ABSTRACT FROM AUTHOR]

Abstract: Ionic liquids (ILs) are typically mixed together and/or with conventional solvents, and other organic and inorganic compounds to inhibit unfavorable characteristics. Methanol is a widely used solvent and additive in many industrial applications and can be beneficially combined with ILs. Ionic liquids in isolation have some intrinsic disadvantages such as high viscosity. Pumping viscous liquids is a challenge for most industrial applications. This undesirable feature is typically tackled by combining ILs with specific solvents. Here, the binary attributes of IL-solvent combinations are assessed and correlated utilizing 731 data records from published sources. A support vector machine (SVM) algorithm is applied to establish reliable correlations between binary density of the IL systems and the methanol component they contain. Error analysis of the results suggests that the proposed SVM model is highly reliable for the purpose of determining the density of IL-methanol systems with a high degree of accuracy such as coefficient of determination (R¯) of greater than 0.99.Graphical abstract: [ABSTRACT FROM AUTHOR]