The human adenovirus PI3K-Akt activator E4orf1 is targeted by the tumor suppressor p53.

Human adenoviruses (HAdV) are classified as DNA tumor viruses due to their potential to mediate oncogenic transformation in non-permissive mammalian cells and certain human stem cells. To achieve transformation, the viral early proteins of the E1 and E4 regions must block apoptosis and activate proliferation: the former predominantly through modulating the cellular tumor suppressor p53 and the latter by activating cellular pro-survival and pro-metabolism protein cascades, such as the phosphoinositide 3-kinase (PI3K-Akt) pathway, which is activated by HAdV E4orf1. Focusing on HAdV-C5, we show that E4orf1 is necessary and sufficient to stimulate Akt activation through phosphorylation in H1299 cells, which is not only hindered but repressed during HAdV-C5 infection with a loss of E4orf1 function in p53-positive A549 cells. Contrary to other research, E4orf1 localized not only in the common, cytoplasmic PI3K-Akt-containing compartment, but also in distinct nuclear aggregates. We identified a novel inhibitory mechanism, where p53 selectively targeted E4orf1 to destabilize it, also stalling E4orf1-dependent Akt phosphorylation. Co-IP and immunofluorescence studies showed that p53 and E4orf1 interact, and since p53 is bound by the HAdV-C5 E3 ubiquitin ligase complex, we also identified E4orf1 as a novel factor interacting with E1B-55K and E4orf6 during infection; overexpression of E4orf1 led to less-efficient E3 ubiquitin ligase-mediated proteasomal degradation of p53. We hypothesize that p53 specifically subverts the pro-survival function of E4orf1-mediated PI3K-Akt activation to protect the cell from metabolic hyper-activation or even transformation.IMPORTANCEHuman adenoviruses (HAdV) are nearly ubiquitous pathogens comprising numerous subtypes that infect various tissues and organs. Among many encoded proteins that facilitate viral replication and subversion of host cellular processes, the viral E4orf1 protein has emerged as an intriguing yet under-investigated player in the complex interplay between the virus and its host. Nonetheless, E4orf1 has gained attention as a metabolism activator and oncogenic agent, while recent research is showing that E4orf1 may play a more important role in modulating the cellular pathways such as phosphoinositide 3-kinase-Akt-mTOR. Our study reveals a novel and general impact of E4orf1 on host mechanisms, providing a novel basis for innovative antiviral strategies in future therapeutic settings. Ongoing investigations of the cellular pathways modulated by HAdV are of great interest, particularly since adenovirus-based vectors actually serve as vaccine or gene vectors. HAdV constitute an ideal model system to analyze the underlying molecular principles of virus-induced tumorigenesis.

Additional new species of Xenodidymella from pasture-medicinal plants in Iran.

Xenodidymella species have a wide range of hosts and can be found as pathogens and saprobes. In this study, two new species of Xenodidymella were found from leaf diseases of three pasture-medicinal plants in Ilam Province, in the west of Iran, and proposed here as X. ilamica and X. scandicis spp. nov. These species were identified based on morphological features and phylogenetic analyses of the internal transcribed spacer regions 1 & 2 and 5.8S nrDNA (ITS), partial beta-tubulin gene (tub2), and partial RNA polymerase II second largest subunit (rpb2) gene. The four Xenodidymella strains isolated in this study were delimited into two sister clades, with the two isolates of X. ilamica from the leaf spot of Colchicum speciosum and Ficaria kochii and two isolates of X. scandicis from leaf blight of Scandix pecten-veneris. Morphologically, X. scandicis produces larger, ostiolate or poroid pycnidia in vitro, while pycnidia in the cultures of X. ilamica are non-ostiolate and smaller. Some pycnidia in old cultures of X. scandicis produce a neck, but a distinct neck in X. ilamica has not been observed. Moreover, three plants under study are new hosts for the genus Xenodidymella.

The impact of continuous and intermittent supportive counseling on self-efficacy and continuation of breastfeeding in lactating women affected by COVID-19: a quasi-experimental trial.

BACKGROUND: Promoting exclusive breastfeeding can have a great effect in reducing the complications and mortality rate of mother and child. OBJECTIVE: The study aimed to compare the effects of continuous and intermittent supportive counselling on the self-efficacy and continuity of breastfeeding among Lactating mothers with COVID-19. METHODS: The study was a semi-experimental research method and was conducted on 73 mothers with COVID-19 who were hospitalized in Ayatollah Mousavi Hospital in Zanjan, Iran from May 2021 to April 2022. In the continuous counselling group, counselling was provided daily for 14 days, while in the intermittent counselling group, counselling was provided once a week for four weeks. Breastfeeding continuity was assessed based on the World Health Organization's classification, and breastfeeding self-efficacy was measured using Dennis' standard breastfeeding self-efficacy questionnaire (BSE) up to four months after delivery. The data were analyzed using chi-square tests, independent t-tests, paired t-tests, analysis of variance with repeated measures, and survival analysis (Kaplan-Meier) with a 95% confidence level. RESULTS: The survival analysis revealed that the cessation of exclusive breastfeeding occurred in 17 cases within the continuous counselling group and in 22 cases within the intermittent counselling group. The rates of continuation for exclusive breastfeeding were 52.8% and 40.5% in the continuous and intermittent counselling group respectively. However, no statistically significant differences were observed in the continuation of breastfeeding and the trend of changes in the mean scores of breastfeeding self-efficacies between the continuous and intermittent counselling groups. Furthermore, comparing the change in breastfeeding self-efficacy scores between the one-month and four-month follow-ups within the continuous counselling group, a statistically significant increase was observed. CONCLUSION: The results indicated no difference in the effectiveness of continuous and intermittent counseling methods in improving breastfeeding continuity in women with COVID-19. Further research is needed to explore the long-term effects of different counseling approaches on breastfeeding outcomes during crises. TRIAL REGISTRATION: The study was registered on the Iranian Registry of Clinical Trials website on 29/06/2021 with the registration code IRCT20150731023423N19. It can be accessed via this link: https://irct.behdasht.gov.ir/user/trial/55391/view .

Comparison of psychological reactions, fear of negative evaluation and mood-emotional alexithymia in successful and unsuccessful people in addiction recovery: a survey of Baluchestan in Iran.

The aim of this study was to examine psychological responses, fear of negative evaluation, and mood-related alexithymia in individuals in addiction recovery who have succeeded versus those who have not. This study employed a causal-comparative design. The research focused on all individuals who sought treatment for addiction at clinics within a specific district in Zahedan city, Iran. Out of the group, 100 individuals were chosen (50 who successfully stopped their addiction and 50 who were unsuccessful in their attempts to quit) through convenience sampling. Data were gathered using the depression, Anxiety, and Stress Scale (DASS-21), Lori's fear of negative evaluation scale, and Toronto's mood-emotional alexithymia scale. Data were examined through both descriptive statistics and multivariate analysis of variance. Based on the results, successful and unsuccessful individuals in addiction recovery showed varying levels of depression, stress, fear of negative evaluation, and having no fear of negative evaluation (p < .01). In simpler terms, unsuccessful individuals in addiction recovery scored higher in depression, stress, fear of negative evaluation, inability feeling emotions, inability to express feelings compared to successful individuals. But successful individuals in addiction recovery obtained higher mean scores than unsuccessful individuals in addiction recovery on having no fear of negative evaluation. According to the findings psychological reactions, fear of negative evaluation and mood-emotional alexithymia play a significant role in addiction treatment and can be helpful in addiction recovery in unsuccessful people in addiction recovery. It is feasible to enhance the effectiveness of addiction recovery by implementing interventions that target the reduction of depression, stress, fear of negative evaluation, and alexithymia.

Characterization and Evaluation of Nano-niosomes Encapsulating Docetaxel against Human Breast, Pancreatic, and Pulmonary Adenocarcinoma Cancer Cell Lines.

Background: Docetaxel (DXL) is an antineoplastic agent for cancer treatment, the therapeutic efficiency of which is limited due to low solubility, hydrophobicity, and tissue specificity. Objective: In this study, nano-niosomes were introduced for improving therapeutic index of DXL. Material and Methods: In this experimental study, two nano-niosomes were synthesized using Span 20® and Span 80® and a thin film hydration method with DXL loading (DXL-Span20 and DXL-Span80). Characterization, in-vitro cytotoxicity and bioavailability of the nano-niosomes was also evaluated via in-vivo experiments. Results: DXL-Span20 and DXL-Span80 have vesicles size in a range of 84-90 nm and negative zeta potentials. DXL entrapment efficiencies were obtained as 69.6 and 74.0% for DXL-Span20 and DXL-Span80, respectively; with an in-vitro sustained release patterns. Cytotoxicity assays were performed against MDA-MB-231, Calu-6, and AsPC-1 cell lines, and the results indicated that DXL loading into nano-niosomes led to decrement in values of half-maximal inhibitory concentration (IC50) at least 2.5 times and at most 6.5 times, compared to free DXL. Moreover, the rat blood bioavailability of DXL after intraperitoneal administration and the pharmacokinetic parameters indicated higher DXL plasma level and the higher effectiveness of DXL-Span80 compared to DXL-Span20. Conclusion: Carrying DXL by the nano-niosomes led to enhanced cytotoxicity (and lower IC50 values) and higher efficacy with enhanced pharmacokinetic parameters.

Microplastics removal efficiency and risk analysis of wastewater treatment plants in Oman.

Microplastics (MPs) have recently been documented as an emerging pollutant that poses a critical threat to environment. Wastewater treatment plants (WWTPs) are commonly regarded as significant contributors to the presence of MPs. This study aimed to assess the MPs load of three wastewater treatment facilities in Oman using various treatments, including MBR, SBR, and CAS. Wastewater samples from influent, effluent, and sludge were collected and analyzed to determine the concentration, morphology, size, color, and polymer type of the MPs. A set of sieves with a mesh size range of 1 mm-45 µm was used to for filtration. Oxidation treatment was applied for all samples using Fenton's reagent, followed by density separation by sodium chloride solution. The Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR- FTIR) method was utilized to test 10% from each sampling point to confirm the polymer types of the MPs. The pollution load index (PLI) and hazard index (HI) have been employed to assess the risk associated with the chemical toxicity and concentration of detected particles. The PROMETHEE method was used to rank the risk of sampling sites based on different criteria that posed potential ecological and human health risks. The results indicate that the average concentrations of 0.99 MP/L, 1.38 MP/L, and 0.93 MP/L were detected in the final treated effluent of WWTP A, WWTP B, and WWTP C, respectively. These concentrations correspond to overall removal efficiencies of 82.5%, 77.4%, and 79.2% for WWTP A, WWTP B, and WWTP C, respectively Most MPs found in tertiary effluent were smaller particles (425 µm) and fiber-shaped. The major types of MPs were polypropylene (PP), low-density polyethylene (LDPE), polyurethane (PU), polyethylene terephthalate (PET), and Polyvinyl chloride (PVC). This study showed that treated effluent and sludge release significant MPs into the environment.

Liposomal factor VIII as an efficient pharmaceutical system for the treatment of hemophilia.

Objectives: Currently, the most important treatment approach for hemophilia type A is recombinant Factor VIII. However, due to its low retention time in the blood, the patients usually need successive injections. In addition, neutralization of injected proteins by antibodies complicates treatment. We examined the prolongation of the persistence time of injectable FVIII in the blood and the potential effects on survival using promising PEGylated liposomes (PEGLip) utilizing hydrogenated soy phosphatidylcholine (HSPC, Tm= 54.5 ºC) and 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC, Tm= - 2 ºC). Materials and Methods: Nanoliposomes with different percentages of PEG (3% and 5%) were obtained via the thin film hydration procedure and extrusion. Liposomal FVIII formulation was prepared and characterization was done. Results: The results revealed that the formulations are in the 80-120 nm range with uniform dispersion, which was confirmed using transmission electron microscopy (TEM) imaging. The phase transition temperature (Tm) of the liposomes was obtained by differential scanning calorimetry (DSC). With an attachment efficacy of approximately 87%, proteins bind non-covalently yet with a strong affinity to the exterior of PEGLip. The final formulations underwent additional examination. No significant change was observed in size, charge, and PDI between the FVIII-conjugated liposomal formulations and their liposomal nanoparticles. The selected formulations were injected into BALB/c mice. The circulation time and potential clotting effectiveness of PEGLip-FVIII are vastly improved over free protein, in non-hemophilic mice. Conclusion: The obtained results showed that using phospholipids with high Tm (HSPC) can improve the hemostatic efficiency of liposomes more than phospholipids with low Tm (POPC).

Machine Learning-Driven Advancements in Liposomal Formulations for Targeted Drug Delivery: A Narrative Literature Review.

Nanoliposomal formulations, utilizing lipid bilayers to encapsulate therapeutic agents, hold promise for targeted drug delivery. Recent studies have explored the application of machine learning (ML) techniques in this field. This study aims to elucidate the motivations behind integrating ML into liposomal formulations, providing a nuanced understanding of its applications and highlighting potential advantages. The review begins with an overview of liposomal formulations and their role in targeted drug delivery. It then systematically progresses through current research on ML in this area, discussing the principles guiding ML adaptation for liposomal preparation and characterization. Additionally, the review proposes a conceptual model for effective ML incorporation. The review explores popular ML techniques, including ensemble learning, decision trees, instance- based learning, and neural networks. It discusses feature extraction and selection, emphasizing the influence of dataset nature and ML method choice on technique relevance. The review underscores the importance of supervised learning models for structured liposomal formulations, where labeled data is essential. It acknowledges the merits of K-fold cross-validation but notes the prevalent use of single train/test splits in liposomal formulation studies. This practice facilitates the visualization of results through 3D plots for practical interpretation. While highlighting the mean absolute error as a crucial metric, the review emphasizes consistency between predicted and actual values. It clearly demonstrates ML techniques' effectiveness in optimizing critical formulation parameters such as encapsulation efficiency, particle size, drug loading efficiency, polydispersity index, and liposomal flux. In conclusion, the review navigates the nuances of various ML algorithms, illustrating ML's role as a decision support system for liposomal formulation development. It proposes a structured framework involving experimentation, physicochemical analysis, and iterative ML model refinement through human-centered evaluation, guiding future studies. Emphasizing meticulous experimentation, interdisciplinary collaboration, and continuous validation, the review advocates seamless ML integration into liposomal drug delivery research for robust advancements. Future endeavors are encouraged to uphold these principles.

Influence of film thickness on structural, optical, and electrical properties of sputtered nickel oxide thin films.

Utilizing radio frequency magnetron sputtering, we successfully fabricated nickel oxide thin films with different thickness (from 80 to 270 nm), and conducted an in-depth examination of their structural, morphological, optical, and electrical properties. The crystal structure and surface roughness were determined using x-ray diffraction (XRD) and atomic force microscopy (AFM), respectively. The XRD analyses showed that the films were composed of cubic nickel oxide, exhibiting a notable orientation along the (200) direction. This crystal texture partially increased when the film thickness reached 270 nm. In addition, a direct correlation between film thickness and crystallite size was observed, with the latter increasing as the former did. AFM analysis provided insights into the surface morphology, revealing metrics like the bearing area, 3D surfaces intersections, and statistical properties of surface height. These insights underscore the relationship between film thickness and surface properties, which in turn influence the overall electrical, and prominently, optical properties of the films. Employing transmittance UV-visible spectroscopy, we characterized the optical behavior of these films, noting a proportional increase in refractive index with film thickness. Additionally, resistivity was observed to increase concomitantly with film thickness. In conclusion, the deposition process's film thickness acts as a pivotal parameter for fine-tuning the structural, morphological, and optical properties of nickel oxide thin films. This knowledge paves the way for optimizing nickel oxide-based devices across various applications. RESEARCH HIGHLIGHTS: We synthesized and characterized of p-type semiconducting NiO thin films sputtered on substrates by using RF magnetron sputtering with different thickness. Advanced crystalline structures and fractal features extracted from XRD and AFM analysis.  The 2D and 3D surface analysis of the samples indicates a complex structure with an imperfect self-similarity that suggests a multifractal structure. We represented graphically the relative representation of higher geometric objects in the AFM image. We attributed the optical and electrical properties of the samples to the crystallite size, and the concurrent reduction in oxygen vacancies and crystalline defects within the films.

Environmental exposure and respiratory health: Unraveling the impact of toxic release inventory facilities on COPD prevalence.

This cross-sectional geospatial analysis explores the prevalence of Chronic Obstructive Pulmonary Disease (COPD) concerning the proximity to toxic release inventory (TRI) facilities in Jefferson County, Alabama. Employing the fuzzy analytical hierarchy process (FAHP), the study evaluates COPD prevalence, comorbidities, healthcare access, and individual health assessments. Given the mounting evidence linking environmental pollutants to COPD exacerbations, the research probes the influence of TRI sites on respiratory health, integrating Geographic Information Systems (GIS) to scrutinize the geospatial vulnerability of communities neighboring TRI sites. Socio-demographic disparities, economic conditions, and air pollution are emphasized in the analysis. The EPA's Toxic Release Inventory serves as the cornerstone for assessing the association between TRI proximity and COPD prevalence. The analysis uncovers a notable inverse correlation between distance from TRI sites and COPD prevalence, signaling potential health risks for populations residing closer to these facilities. Moreover, factors such as minority status, low income, and air pollution are associated with higher COPD prevalence, underscoring the imperative of comprehending the interplay between environmental exposure and respiratory health. This study bridges gaps in the literature by addressing the geographical nexus between COPD prevalence and pollution exposure. By leveraging FAHP, the research furnishes a holistic understanding of the multifaceted factors influencing vulnerability to COPD. The findings underscore the necessity for targeted public health interventions and policy measures to redress environmental disparities and alleviate the repercussions of TRI facilities on respiratory health.

Evaluation of the satisfaction and experiences of oncology patients and doctors using teleconsultation during the COVID-19 pandemic.

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic, the Gustave Roussy Cancer Center introduced teleconsultation via telephone, as an alternative to face-to-face consultation to reduce patient hospital visits. This study was designed to assess patient and doctor satisfaction with this modality of care in oncology patient care during the period of the pandemic and beyond. METHODS: We designed two questionnaires based on validated scores to assess satisfaction from teleconsultation in patients (EORTC OUT-PATSAT 35 and Telemedicine Satisfaction Questionnaire [TSQ] scores) and doctors (Telehealth Usability Questionnaire [TUQ]), and anxiety levels in both groups (anxiety section of the Hospital Anxiety and Depression Scale [HADS], HADS-A). These were electronically sent to patients and doctors with experience of at least one remote consultation during the first wave of the COVID-19 pandemic. RESULTS: 239 patients and 32 doctors were eligible for the analyses. In the patient group, the mean satisfaction scores were 79.5 (SD 18.1) and 74.92 (SD 15.3) for EORTC OUT-PATSAT 35 and TSQ, respectively. In the doctor group, the mean satisfaction scores were 67.1 (SD 12.7) and 64.9 (SD 13.9) for TUQ and TUQ for Skype for Business, respectively. 65.7% of patients and 81.2% of doctors had no/low anxiety. Univariable analyses in patients showed correlation of the EORTC OUT-PATSAT 35 and TSQ scores with anxiety and gender, with lower mean scores in women compared to men. Multivariable analysis showed correlation of the EORTC OUT-PATSAT 35 and TSQ scores to anxiety in both patients and doctors. CONCLUSIONS: Teleconsultation via telephone is an acceptable modality of care for oncology patients, with high satisfaction from its implementation during the pandemic reported by patients and doctors. This was consistent across responder groups with different characteristics. An individualized approach to patients should be implemented for the safe and effective use of teleconsultation in oncology beyond the pandemic.

A nanoemulsion-based delivery system for imatinib and in vitro anticancer efficacy

A self-nanoemulsifying drug delivery system (SNEDDS) composed of ethyl oleate, Tween 80 and polyethylene glycol 600 was prepared as a new route to improve the efficacy of imatinib. The drug-loaded SNEDDS formed nanodroplets of ethyl oleate stabilized by Tween 80 and polyethylene glycol 600 with a diameter of 81.0±9.5 nm. The nanoemulsion-based delivery system was stable for at least two months, with entrapment efficiency and loading capacity of 16.4±0.1 and 48.3±0.2%, respectively. Imatinib-loaded SNEDDS was evaluated for the drug release profiles, and its effectiveness against MCF-7 cell line was investigated. IC50 values for the imatinib-loaded SNEDDS and an imatinib aqueous solution were 3.1 and 6.5 µg mL-1, respectively.

Isolation and characterization of phenol degrading yeasts from wastewater in the coking plant of Zarand, Kerman

Abstract Phenol and phenolic compounds are environmental pollutants present in industrial wastewaters such as coal tar, oil refineries and petrochemical plants. Phenol removal from industrial effluents is extremely important for the protection of environment. Usually, phenol degradation is carried out by physicochemical methods that are costly and produce hazardous metabolites. Recently, phenol biodegradation has been considered. Yeasts are the most important phenol biodegraders. In this study, the phenol-degrading yeast from environmental samples (soil and wastewater) was isolated from the coking plant of Zarand, Kerman. Then total heterotrophic yeasts were counted. The soil samples had higher rates of yeast degrader, in comparison to wastewater samples. After three passages, four yeasts (K1, K2, K7 and K11) that had the highest growth rate were selected for further study. Also, these yeasts were able to remove phenol measured by Gibbs reagent. The effect of four different concentrations of phenol (50, 125, 200 and 275) mg L−1 was measured and three degradation patterns in these yeasts were observed. The hydrophobicity and emulsification activity were measured in all eleven yeasts. Finally, strong yeasts in phenol degrading yeasts were identified by molecular method using amplification of 18S rRNA gene region. The sequencing results showed that these isolated yeasts belonged to Candida tropicalis strain K1, Pichia guilliermondii strain K2, Meyerozyma guilliermondii strain K7 and C. tropicalis strain K11.