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The present article formally studies the propagation of optical pulses in a nonlinear medium governed by the nonlinear Kodama equation. For this purpose, the Lie symmetries group is first adopted for similarity reduction and constructing some exact solutions of the governing equation. After deriving the dynamical system of the nonlinear Kodama equation, its bifurcation analysis is accomplished using the idea of the planar dynamical system. Through perturbing the resultant dynamical system using a trigonometric function, chaotic characteristics of the governing model are analyzed by serving several two- and three-dimensional phase portraits. A sensitivity analysis of the dynamical system is performed using the Runge–Kutta method to ensure that small changes in initial conditions have little impact on solution stability. Finally, using the technique of the planar dynamical system, a number of Jacobi elliptic function solutions (in special cases, bright and dark solitons) are constructed for the nonlinear Kodama equation. It has been shown that bright and dark solitons can be controlled for their width and height effectively by the achievements of the current paper.

In the present study, the feasibility of planting ash (Fraxinus excelsior L.) and spruce (Picea abies L.) tree species was investigated for rehabilitation of the Toroq Watershed in the northeast of Iran. The estimated land suitability indices ranged from 23.95 to 71.05, and 22.47 to 69.38 for ash and spruce plantations by parametric approach, categorized into moderately suitable (S2) in the east to not suitable (N) in the middle and western parts of the study area. The values of land indices by the AHP approach varied between 35.45 to 94.09 and 34.67 to 83.98 for ash and spruce plantations ranging from highly suitable (S1) in the east to moderately suitable (S2) in the middle and scattered parts in the east and not suitable (N) in the north and southwest of the basin. The results showed that the most important limitations were climate, elevation, soil depth, and soil texture. The regression coefficient (R2) of land suitability indices between parametric and AHP approaches for the two spices was 0.894 and 0.866 respectively. The results of the two models revealed that the moderately suitable class S2 is dominant for ash and spruce plantations in the eastern parts of the basin, while the middle and western parts of the basin were not suitable for plantation of the trees. The findings of this study may help land-use planners to rehabilitate the watershed by expanding forest plantation which ecologically tolerates extreme conditions of the region.

Plant Genetic Resources (PGRs) are one of the most valuable natural resources of anycountry. Biotechnology through genetic engineering of plants and the creation of new plantvarieties can increase the value of these resources. Different technical and legalmechanisms such as ex situ/in situ collection of PGRs, and Intellectual Property Rights(IPRs) indicate also an international institutional effort for sustainable use of biodiversity.Investigating international developments in the fields of exploitation and conservation ofPGRs is therefore essential. The main purpose of this manuscript is to explore criteria thatinternational legal instruments use for creating an appropriate interaction betweenconservation and exploitation of PGRs. These instruments have been especially developedin the two systems of international environmental law and intellectual property rights.Based on a descriptive analysis method, this research attempted to examine the provisionsof these two legal instruments. Research findings indicate that intellectual property rightsencourages the creation and development of green technologies, especially agrobiotechnology and protects Traditional Knowledge (TK) associated with PGRs as anappropriate tool for the sustainable exploitation of PGRs when implemented in aresponsible manner. International environmental law paves also the way for biodiversityconservation through creation of binding and non-binding obligations for preservinggenetic diversity on the planet. Sustainable conservation of PGRs requires an appropriateinteraction between the two legal systems.

Abstract Background Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women. The purpose of this study is to evaluate the effects of Stachys sylvatica hydroalcoholic extract on biochemical and histological parameters in a rat model of polycystic ovary syndrome. Thirty adult female Wistar rats with an average weight of 180 g were divided into five groups of six rats. Animals were divided into groups of control, PCOS (intramuscular injection of 2 mg estradiol valerate, Aburaihan Co., Iran/rat, once), and treated with hydroalcoholic extract of Stachys sylvatica. After 60 days of PCOS induction, 100, 250, and 500 mg/kg BW Stachys sylvatica hydroalcoholic extract were injected intraperitoneally. The control group was just injected with olive oil as a solvent. After 10 days of treatment, animals were weighed and then sacrificed and blood samples were taken from their heart for hormonal studies. Ovaries of all groups were cut for histological studies and fixed in formaldehyde, and 7-μm sections were prepared by microtome and stained using hematoxylin–eosin. The data were analyzed by one-way ANOVA and Tukey-Kramer post hoc test with the SPSS software. The significant level was p

The ion exchange creates the optical buried waveguides, whereas it is the method that the glass doping occurs with the condition of existence of the mobile metal ions. The most common ion used is silver (Ag+) due to its broad variation in the refractive index. The proposed application presented in this work is to use the microring resonator (MRR) system based on the buried waveguides simulated by the ion exchange method. The passive MRRs are realized as the multi-wavelength transceiver, applicable in optical technologies such as the optical sensing, Terahertz (THz) communication and optical switching. The cross-sectional view of the simulated buried optical waveguide for the Ag+ concentrations of 0.8 mol/m3 is presented. The fundamental mode propagation is simulated using the time-domain traveling wave method, where the simulation of the optical power flow density and the electric field distributions of the buried waveguides were performed. The two coupled MRRs are used to generate tunable dual-wavelength with spacing in the range of Terahertz (THz). As results, the dual wavelengths in the range between 0.25 and 0.96 THz were generated at the throughput and drop port of the MRRs system. Keywords: Waveguides, Ring resonator, Coupled ring resonators, Ion exchange

We demonstrate a stable, tunable dual-wavelength (DW) generated by launching an in-house built supercontinuum (SC) into an add-drop microring resonator (MRR). The MRR is fabricated from a silicon–nitrogen–oxygen substrate. The frequency comb of the filtered SC is obtained with an experimental free spectral range (FSR) from 0.39 to 0.46 nm corresponding to 48.7–57 GHz within the wavelength range 1520–1660 nm. The stability of a generated DW within the ranges 1561.16 and 1561.57 nm over 120 min is examined, where high, stable DW with a very low power fluctuation is achieved. This work has demonstrated the use of waveguide based MRR in the fiber laser system, and a remarkable flat and low power fluctuations frequency comb is achieved using the in-house built SC source and MRR. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE: Candida albicans infection is a problem of growing clinical importance, particularly in immunocompromised populations. This study aimed to investigate the inhibitory effect of carvacrol on the hyphae formation and expression of C. albicans HWP1. METHODS: This cross-sectional study was done over a 6-month period in 2016-2017. Vaginal, mouth and skin surface swabs were obtained from immunocompromised patients. Colonizing clinical isolates of C. albicans were identified and drug susceptible isolates detected using WHONET software. The susceptibility test for carvacrol (range 6.25–300 μg/ml) were carried out with a broth microdilution according to the CLSI guidelines against drug susceptible C. albicans. The time kill assay of carvacrol (range 2 × MIC to ¼ × MIC) was determined. Hyphae inhibition was evaluated by light microscopy. We determined the expression levels of HWP1 implicated in hyphae formation of C. albicans ATCC 14053 cells by quantitative RT-PCR. FINDINGS: Ten colonizing clinical isolates of drug susceptible C. albicans were identified. Carvacrol was inhibited the growth of all drugs susceptible isolates of C. albicans (MIC range, 25-200 µg/ml). Time kill curve assay demonstrated that carvacrol could significantly inhibit the growth of C. albicans (p≤0.05). Carvacrol efficiently prevented hyphae formation in drug susceptible C. albicans. The expression levels of HWP1 gene were down-regulated by 1.82- and 1.62-fold at concentrations of 2 × MIC and 1×MIC of carvacrol, respectively. CONCLUSION: These results suggest that carvacrol could provide an improved and safe clinical approach in treating Candida infections by prevention of hyphae formation.

BACKGROUND AND OBJECTIVE: Health promoting lifestyle is any kind of action that is taken to maintain the health of the individual. Healthy lifestyle plays an important role in improving the maternal-fetal outcomes. The aim of this study is to determine the effect of training pregnant women and their husbands on health promoting lifestyle. METHODS: This clinical trial was conducted among 189 pregnant women in the city of Bukan, Iran. Participants were categorized into three groups: the recipients of the training along with their husbands (the first intervention group), the recipients of the training without their husbands (the second group of intervention) and the routine care recipients (control group). Four sessions of group training were held for mothers of both interventional groups and one group training session was held for the mothers of the first intervention group regarding sleep health, nutrition, physical activity, self-image and sexual issues. Health promoting lifestyle questionnaire (score range: 52 - 208) was completed and assessed before the intervention, eight weeks after the intervention and six weeks after delivery. FINDINGS: There was no statistically significant difference between the groups before the intervention in terms of the total score of health promoting lifestyle. Eight weeks after the intervention, the mean score of health promoting lifestyle was 162.2±2.5 in the first group, 153.6±2.5 in the second group and 133.4±2.4 in the control group, which was significantly higher in both intervention groups compared to the control group (p

The baculovirus expression vector system (BEVS) is a powerful tool in pharmaceutical biotechnology to infect insect cells and produce the recombinant proteins of interest. It has been well documented that optimizing the culture condition and its supplementation through designed experiments is critical for maximum protein production. In this study, besides physicochemical parameters including incubation temperature, cell count of infection, multiplicity of infection, and feeding percentage, potential supplementary factors such as cholesterol, polyamine, galactose, pluronic-F68, glucose, L-glutamine, and ZnSO4 were screened for Spodoptera frugiperda (Sf9) cell culture and expression of hemagglutinin (HA) protein of Influenza virus via Placket-Burman design and then optimized through Box-Behnken approach. The optimized conditions were then applied for scale-up culture and the expressed r-HA protein was characterized. Optimization of selected parameters via the Box-Behnken approach indicated that feed percentage, cell count, and multiplicity of infection are the main parameters affecting r-HA expression level and potency compared to the previously established culture condition. This study demonstrated the effectiveness of designing experiments to select and optimize important parameters that potentially affect Sf9 cell culture, r-HA expression, and its potency in the BEVS system., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alizadeh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Colon cancer, ranked as the fourth leading global cause of cancer death, exhibits a complex progression marked by genetic variations. Over the past decade, the utilization of diverse CRISPR systems has propelled accelerated research into colorectal cancer (CRC) treatment., Areas Covered: CRISPR/Cas9, a key player in this research, identifies new oncogenes, tumor suppressor genes (TSGs), and drug-resistance genes. Additionally, it facilitates the construction of experimental models, conducts genome-wide library screening, and develops new therapeutic targets, especially for targeted knockout in vivo or molecular targeted drug delivery, contributing to personalized treatments and significantly enhancing the care of colon cancer patients. In this review, we provide insights into the mechanism of the CRISPR/Cas9 system, offering a comprehensive exploration of its applications in CRC, spanning screening, modeling, gene functions, diagnosis, and gene therapy. While acknowledging its transformative potential, the article  highlights the challenges and limitations of CRISPR systems., Expert Opinion: The application of CRISPR/Cas9 in CRC research provides a promising avenue for personalized treatments. Its potential for identifying key genes and enabling experimental models and genome-wide screening enhances patient care. This review underscores the significance of CRISPR-Cas9 gene editing technology across basic research, diagnosis, and the treatment landscape of colon cancer.

Purpose: Glioblastoma (GBM) stands out as the most prevalent and aggressive intracranial tumor, notorious for its poor prognosis. The current standard-of-care for GBM patients involves surgical resection followed by radiotherapy, combined with concurrent and adjuvant chemotherapy using Temozolomide (TMZ). The effectiveness of TMZ primarily relies on the activity of O 6 -methylguanine DNA methyltransferase (MGMT), which removes alkyl adducts from the O 6 position of guanine at the DNA level, thereby counteracting the toxic effects of TMZ., Method: In this study, we employed fusions of catalytically-inactive Cas9 (dCas9) to DNA methyltransferases (dCas9-DNMT3A) to selectively downregulation MGMT transcription by inducing methylation at MGMT promoter and K-M enhancer., Result: Our findings demonstrate a significant reduction in MGMT expression, leading to intensified TMZ sensitivity in the HEK293T cell line., Conclusion: This study serves as a proof of concept for the utilization of CRISPR-based gene suppression to overcome TMZ resistance and enhance the lethal effect of TMZ in glioblastoma tumor cells., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Growing resistance toward ribosome-targeting macrolide antibiotics has limited their clinical utility and urged the search for superior compounds. Macrolones are synthetic macrolide derivatives with a quinolone side chain, structurally similar to DNA topoisomerase-targeting fluoroquinolones. While macrolones show enhanced activity, their modes of action have remained unknown. Here, we present the first structures of ribosome-bound macrolones, showing that the macrolide part occupies the macrolide-binding site in the ribosomal exit tunnel, whereas the quinolone moiety establishes new interactions with the tunnel. Macrolones efficiently inhibit both the ribosome and DNA topoisomerase in vitro. However, in the cell, they target either the ribosome or DNA gyrase or concurrently both of them. In contrast to macrolide or fluoroquinolone antibiotics alone, dual-targeting macrolones are less prone to select resistant bacteria carrying target-site mutations or to activate inducible macrolide resistance genes. Furthermore, because some macrolones engage Erm-modified ribosomes, they retain activity even against strains with constitutive erm resistance genes., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: The aim of this study was to investigate the television (TV) consumption patterns (viewing behavior and motivation) of older adults in Wuhan, China, during the COVID-19 pandemic and its impact on older adults' mental health, particularly in relation to COVID-19-induced fear., Participants and Methods: A questionnaire survey was conducted with 405 older adults in Wuhan, China. The data were analyzed using a structural equation model to understand the relationship between TV viewing behavior, motivation, and fear related to COVID-19., Results: The findings indicate that the motivation to watch TV has a positive influence on viewing behavior among older adults during the pandemic. However, this motivation negatively impacts their COVID-19-related fear. Furthermore, a negative correlation was observed between viewing behavior and fear. The primary motivations for TV viewing among older adults during the pandemic were identified as social interaction and emotion management, followed by information seeking and value expression., Conclusion: The findings suggest that TV viewing plays a significant role in the mental well-being of older adults during the COVID-19 pandemic. By addressing the motivations of social interaction, emotion management, information seeking, and value expression, public health organizations and TV stations can contribute to the mental health of this vulnerable population., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Yu and Alizadeh.)

Background: It has been suggested that metabolic syndrome (MetS) accelerates the aging process, potentially contributing to the development of age-related complications. Available studies examining the relation of MetS to telomere length (TL), a putative biological marker of aging, have yielded inconclusive findings. This meta-analysis was performed to investigate the association between MetS and TL., Methods: A comprehensive systematic search was conducted in PubMed and Scopus databases to identify relevant literature published up to February 2024. Standard mean difference (SMD) and standardized beta coefficient (β) with their 95% confidence intervals (CI) were used as effect sizes to measure the associations using the random effects model., Results: A total of nine studies, comprising a total sample size of 8,606 participants, were eligible for the meta-analysis. No significant difference in mean TL was found between patients with and without MetS (SMD = -0.03, 95%CI = -0.17 to 0.10), with a significant heterogeneity across the studies ( I 2 = 89.7.0%, p ≤ 0.001). In contrast, it was revealed that MetS is negatively related to TL (β = -0.08, 95%CI = -0.15 to -0.004). In the subgroup analysis, this finding was supported by the International Diabetes Federation (IDF) definition of MetS., Conclusion: This meta-analysis highlighted that MetS may be linked to a shorter TL. Additional studies are required to confirm this finding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ibraheem Shelash Al-Hawary, Ali Alzahrani, Ghaleb Maabreh, Abed Jawad, Alsaadi, Kareem Jabber, Alawadi, Alsalamy and Alizadeh.)

The treatment of candidiasis infections is hindered by the presence of biofilms. Here, we report the biofilm-associated genes as potential molecular targets by silver nanoparticles (nano-Ag) in Candida albicans. Nano-Ag was biosynthesized using Bacillus licheniformis, Bacillus cereus, and Fusarium oxysporum. The physicochemical properties of the microbial-synthesized of nano-Ag are widely characterized by visual observation, ultraviolet-visible spectroscopy, scanning electron microscopy, X-ray diffraction spectroscopy, and Fourier transform infrared spectroscopy. Characterization results revealed the formation of nano-Ag. Antiplanktonic cells and antibiofilm activities of nano-Ag were also demonstrated by minimum inhibition concentrations (MIC), minimum fungicidal concentration (MFC), MFC/MIC ratio, crystal violet staining, 2,3-bis (2-methoxy-4-nitro-5 sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide (XTT), and microscopic image analysis. We have analyzed the expressions of biofilm-associated genes in C. albicans treated with different concentrations of nano-Ag based on MIC. The expression profile of BCR1, ALS1, ALS3, HWP1, and ECE1 showed downregulated genes involved in these pathways by the treatment with nanoparticles. Negative regulators, TUP1, NRG1, and TOR1, were upregulated by the treatment of nano-Ag. Our study suggests that nano-Ag affects gene expression and may subsequently decrease the pathogenesis of C. albicans by inhibiting biofilm formation. Molecular targeting of biofilm-associated genes involved in biofilm formation by nano-Ag may be an effective treatment strategy for candidiasis infections., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Here, a novel targeted nanostructure complex was designed as an alternative to the traditional treatment approaches for breast cancer. A delivery system utilizing CuS nanoparticles (CuS NPs) was developed for the purpose of targeted administration of doxorubicin (Dox), an anticancer agent. To regulate Dox release, chitosan (CS), a biodegradable and hydrophilic polymer with biocompatible properties, was applied to coat the Dox-loaded CuS NPs. Furthermore, AS1411 aptamer, served as a targeting agent for breast cancer cells (MCF-7 and 4T1 cells), was conjugated with CS-Dox-CuS NPs effectively. To assess the effectiveness of APT-CS-CuS NPs, various methods such as flow cytometry analysis, MTT assay, fluorescence imaging, and in vivo antitumor efficacy were employed. The hollow core and porous surface of CuS NPs improved the Dox loading capacity and entrapment efficiency (almost 100%). The rate of drug release at the tumor site (citrate buffer with pH 5.6) exhibited a marked increase in comparison to that observed within the physiological environment (phosphate buffer with pH 7.4). The targeted formulation (APT-CS-Dox-CuS NPs) significantly increased cytotoxicity of the Dox payload in target cells, including 4T1 (p ≤ 0.0001 (****)) and MCF7 (p ≤ 0.01 (**)) cells compared to CHO cells. Moreover, the ability of tumor growth inhibition of the targeted system was significantly (p ≤ 0.05 (*)) more than free Dox in tumor-bearing mice. The findings indicate that the targeted formulation augmented effectiveness and specificity while minimizing harm to non-targeted cells, signifying its potential as a sophisticated cancer drug delivery system., Competing Interests: Declaration of competing interest There is no conflict of interest about this article., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Objectives: To study the impact of social determinants of health (SDoH) on pediatric extracorporeal membrane oxygenation (ECMO) outcomes., Design, Setting, and Patients: Retrospective study of children (< 18 yr) supported on ECMO (October 1, 2015 to March 1, 2021) using Pediatric Health Information System (44 U.S. children's hospitals). Patients were divided into five diagnostic categories: neonatal cardiac, pediatric cardiac, neonatal respiratory, pediatric respiratory, and sepsis. SDoH included the Child Opportunity Index (COI; higher indicates social advantage), race, ethnicity, payer, and U.S. region. Children without COI were excluded. Diagnostic category-specific clinical variables related to baseline health and illness severity were collected., Interventions: None., Measurements and Main Results: Children supported on ECMO experienced a 33% in-hospital mortality (2863/8710). Overall, children with lower COI, "other" race, Hispanic ethnicity, public insurance and from South or West regions had greater mortality. Associations between SDoH and ECMO outcomes differed between diagnostic cohorts. Bivariate analyses found that only pediatric cardiac patients had an association between COI or race and mortality. Multivariable logistic regression analyses examined relationships between SDoH, clinical variables and mortality within diagnostic categories. Pediatric cardiac patients had 5% increased odds of death (95% CI, 1.01-1.09) for every 10-point decrement in COI, while Hispanic ethnicity was associated with higher survival (adjusted odds ratio [aOR] 0.72 [0.57-0.89]). Children with heart disease from the highest COI quintile had less cardiac-surgical complexity and earlier cannulation. Independent associations with mortality were observed in sepsis for Black race (aOR 1.62 [1.06-2.47]) and other payer in pediatric respiratory patients (aOR 1.94 [1.23-3.06])., Conclusions: SDoH are statistically associated with pediatric ECMO outcomes; however, associations differ between diagnostic categories. Influence of COI was observed only in cardiac patients while payer, race, and ethnicity results varied. Further research should investigate differences between diagnostic cohorts and age groups to understand drivers of inequitable outcomes., Competing Interests: Dr. Newburger’s institution received funding from Pfizer, Bristol Myers Squibb, and Daiichi-Sankyo; she received funding from Bristol Myers Squibb, Novartis, and UpToDate; she disclosed that she is on the Steering Committee for ENOBLATE trial. Dr. Thiagarajan’s institution received funding from the U.S. Department of Defense Clinical Trial (award W81XWH2210301); he received funding from the Society of Critical Care Medicine and Extracorporeal Life Support Organization. Dr. Moynihan received funding from Edwards Life Sciences. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Cervical cancer is the fourth leading cause of cancer-related death in women worldwide. Microbial products are valuable sources of anti-cancer drugs. The aim of this study was to isolate secreted aspartyl proteinase protein from Candida tropicalis, investigate its inhibitory effect on human cervical cancer HeLa cells, and analyze the expression profiling of selected nuclear stem cell-associated transcription factors. The presence of secreted aspartyl proteinase protein was confirmed by the expression of SAP2 and SAP4 genes in C. tropicalis during the yeast-hyphae transition phase. The enzyme was purified and characterized using the aqueous two-phase system purification method, as well as proteolytic activity and the Bradford and micro-Kjeldahl methods, respectively. The in vitro anti-cancer properties of secreted aspartyl proteinase protein were evaluated by MTT assay, microscopic image analysis, nitric oxide (NO) scavenging activity assay, intracellular reactive oxygen species (ROS) production assay, and RT-qPCR. The isolated C. tropicalis secreted aspartyl proteinase protein exhibited proteinase activity with values ranging from 93.72 to 130.70 μg/mL and 89.88-127.72 μg/mL according to the Bradford and micro-Kjeldahl methods, respectively. Secreted aspartyl proteinase showed effective cytotoxicity in HeLa cell line leading to significant morphological changes. Additionally, it exhibited increased free radical scavenging activity compared to the untreated control group, as evidenced by nitrite inhibition. ROS production increased in HeLa cells exposed to secreted aspartyl proteinase. The expression levels of the nuclear stem cell-associated transcription factors octamer-binding transcription factor 4 (OCT4), sex determining region Y-box 2 (SOX2), and Nanog homeobox (NANOG) were significantly downregulated in the HeLa cells treated with secreted aspartyl proteinase. Secreted aspartyl proteinase protein may be a promising anti-cancer agent, as it effectively affects gene expression and may ultimately reduce the development and progression of cervical cancer. Targeting the genes related to nuclear stem cell-associated transcription factors may provide a novel amenable to cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Duchenne Muscular Dystrophy (DMD) is a progressive muscle wasting disorder caused by loss-of-function mutations in the dystrophin gene. Although the search for a definitive cure has failed to date, extensive efforts have been made to introduce effective therapeutic strategies. Gene editing technology is a great revolution in biology, having an immediate application in the generation of research models. DMD muscle cell lines are reliable sources to evaluate and optimize therapeutic strategies, in-depth study of DMD pathology, and screening the effective drugs. However, only a few immortalized muscle cell lines with DMD mutations are available. In addition, obtaining muscle cells from patients also requires an invasive muscle biopsy. Mostly DMD variants are rare, making it challenging to identify a patient with a particular mutation for a muscle biopsy. To overcome these challenges and generate myoblast cultures, we optimized a CRISPR/Cas9 gene editing approach to model the most common DMD mutations that include approximately 28.2% of patients. GAP-PCR and sequencing results show the ability of the CRISPR-Cas9 system to efficient deletion of mentioned exons. We showed producing truncated transcript due to the targeted deletion by RT-PCR and sequencing. Finally, mutation-induced disruption of dystrophin protein expression was confirmed by western blotting. All together, we successfully created four immortalized DMD muscle cell lines and showed the efficacy of the CRISPR-Cas9 system for the generation of immortalized DMD cell models with the targeted deletions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This systematic review and meta-analysis study aimed to evaluate global Trichuris infection prevalence, assessing progress towards the WHO's 2030 target. We searched international databases from 2010-2023, categorizing data by regions and socio-economic variables using a random-effects model. Analyzing 757 articles covering 7154,842 individuals from 78 countries, the study found a pooled global prevalence of (6.64-7.57%), with the highest rates in the Caribbean (21.72%; 8.90-38.18%) and South-East Asia (20.95; 15.71-26.71%) regions. Southern Africa (9.58; 2.11-21.46%), Latin America (9.58; 2.11-21.46%), and Middle Africa Middle Africa (8.94; 6.31-11.98%) also exhibited high prevalence. Eastern Europe had the lowest prevalence at 0.16% (0.09-0.24). Approximately 513 (480-547) million people worldwide were estimated to harbor Trichuris. Moreover ∼1.5% of people tested worldwide (2010-2023) had a moderate to heavy intensity of infection. The study emphasizes the persistent global health threat of Trichuris infection, urging tailored strategies for effective control and prevention on a global scale., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Patients with inborn errors of immunity (IEI) are among the high-risk groups regarding COVID-19. Receiving booster doses (third and fourth) in addition to the standard doses is recommended in these patients. This study investigated the antibody response before and after a booster dose of Sinopharm vaccine in IEI patients.  Thirty patients (>12 years) with antibody deficiencies, referred to Imam Khomeini Hospital and Children's Medical Center in Tehran, were enrolled in this prospective cross-sectional study. All patients were fully vaccinated with the BBIBP-CorV vaccine (2 doses of Sinopharm). Initial measurements of anti-receptor-binding domain (anti-RBD) and anti-nucleocapsid (anti-N) IgG antibody responses were conducted by enzyme-linked immunosorbent assay (ELISA). Subsequently, all patients received a booster dose of the vaccine. Four to six weeks after booster injection, the levels of antibodies were re-evaluated.  Twenty patients with common variable immunodeficiency (CVID), 7 cases with agammaglobulinemia and 3 patients with hyper IgM syndrome were studied. Anti-RBD IgG and anti-N IgG antibodies increased in all patients after the booster. Our results indicated the need of receiving booster doses of the COVID-19 vaccine in patients with antibody deficiencies, even for enhancing humoral immune response specially in patients with CVID.

Objective: To examine characteristics associated with formal ethics consultation (EC) referral in pediatric extracorporeal membrane oxygenation (ECMO) cases, and document ethical issues presented., Design: Retrospective cohort study using mixed methods., Setting: Single-center quaternary pediatric hospital., Patients: Patients supported on ECMO (January 2012 to December 2021)., Interventions: We compared clinical variables among ECMO patients according to the presence of EC. We defined optimal cutoffs for EC based on run duration, ICU length of stay (LOS), and sum of procedures or complications. To identify independent explanatory variables for EC, we used a forward stepwise selection multivariable logistic regression model. EC records were thematically characterized into ethical issues., Measurements and Main Results: Of 601 ECMO patients and 225 patients with EC in 10 years, 27 ECMO patients received EC (4.5% of ECMO patients, 12% of all ECs). On univariate analysis, use of EC vs. not was associated with multiple ECMO runs, more complications/procedures, longer ICU LOS and ECMO duration, cardiac admissions, decannulation outcome, and higher mortality. Cutoffs for EC were ICU LOS >52 days, run duration >160 hours, and >6 complications/procedures. Independent associations with EC included these three cutoffs and older age. The model showed good discrimination (area under the curve 0.88 [0.83, 0.93]) and fit. The most common primary ethical issues were related to end-of-life, ECMO discontinuation, and treatment decision-making. Moral distress was cited in 22 of 27 cases (82%)., Conclusion: EC was used in 4.5% of our pediatric ECMO cases, with most ethical issues related to end-of-life care or ECMO discontinuation. Older age, longer ICU LOS, prolonged runs, and multiple procedures/complications were associated with greater odds for EC requests. These data highlight our single-center experience of ECMO-associated ethical dilemmas. Historical referral patterns may guide a supported decision-making framework. Future work will need to include quality improvement projects for timely EC, with evaluation of impacts on relevant endpoints., Competing Interests: Dr. Alexander’s institution received funding from Novartis. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Several studies have reported vertical transmission of SARS-CoV-2; however, information regarding intrauterine transmission based on diagnostic methods to detect SARS-CoV-2 infection is scarce. A systematic review and meta-analysis was conducted to identify and explore the studies that attempt to ascertain the possibility of intrauterine transmission of SARS-CoV-2 infection according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) statement. The results demonstrate that SARS-CoV-2 can be transmitted intrauterine, as detected by clinical manifestations (1.00, 95 % CI: 1.00 - 1.00, 0.51, 95 % CI: 0.22 - 0.80), imaging (0.50, 95 % CI: 0.24 - 0.76, 0.03, 95 % CI: 0.00 - 0.17), molecular (1. 00, 95 % CI: 1.00 - 1.00, 0.92, 95 % CI: 0.77 - 1.00), immunological (0.32, 95 % CI: 0.10 - 0.57, 0.34, 95 % CI: 0.11 - 0.61), and histological approaches (0.79, 95 % CI: 0.52 - 0.98) in maternal and fetal/neonatal specimens, respectively. The possibility of intrauterine transmission of SARS-CoV-2 from mother to fetus/newborn was 41 % (95 % CI 0.37 - 0.45). We might confirm/verify the intrauterine transmission of SARS-CoCV-2 from mother to fetus/newborn., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rheumatic and congenital heart disease, cardiomyopathies, and hypertensive heart disease are major causes of suffering and death in low- and lower middle-income countries (LLMICs), where the world's poorest billion people reside. Advanced cardiac care in these counties is still predominantly provided by specialists at urban tertiary centers, and is largely inaccessible to the rural poor. This situation is due to critical shortages in diagnostics, medications, and trained healthcare workers. The Package of Essential NCD Interventions - Plus (PEN-Plus) is an integrated care model for severe chronic noncommunicable diseases (NCDs) that aims to decentralize services and increase access. PEN-Plus strategies are being initiated by a growing number of LLMICs. We describe how PEN-Plus addresses the need for advanced cardiac care and discuss how a global group of cardiac organizations are working through the PEN-Plus Cardiac expert group to promote a shared operational strategy for management of severe cardiac disease in high-poverty settings., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

While quadricuspid morphology is commonly observed in truncal valves, quadricuspid aortic valves (QAV) are rare and their natural history is not well described. This retrospective study of 37 patients describes the diagnostic associations and morphologic variability of QAVs in children (median age at diagnosis 4.3 y IQR 0-12 y). Associated congenital heart diseases were present in 54% (most commonly tetralogy of Fallot (TOF) and valvar pulmonary stenosis). Among patients with isolated QAV, 11 had genetic syndrome and 5 had skeletal anomalies. Valve morphology was most commonly type B (41%) and A (35%; Hurvitz and Roberts). Dilated aortic root (Z ≥ 2) was present in 5 and dilated ascending aorta in 9 patients at diagnosis. All patients with type C (n = 3) and G (n = 1) had aortic dilation. At diagnosis, >mild AR was rare (n = 1), mild regurgitation was common (n = 12, 32%), >mild AS was rare (n = 2), and mild AS was uncommon (n = 4). Over a median follow-up of 3.3y (IQR 0.9-11y), progression of AR was seen in 2 patients and progression of aortic root or ascending aorta dilation (increase in Z score by ≥ 2) was seen in 5 patients. In conclusion, QAV is a rare congenital anomaly and about half of the cases are found in hearts that are otherwise structurally normal. A relatively high prevalence is seen in patients with TOF, pulmonary stenosis, skeletal deformities, and genetic syndromes. Meticulous evaluation of aortic valve morphology should be conducted on echocardiograms performed for these indications., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A major revelation of genome-scale biological studies in the post-genomic era has been that two-thirds of human genes do not encode proteins. The majority of non-coding RNA transcripts in humans are long non-coding RNA (lncRNA) molecules, non-protein-coding regulatory transcripts with sizes greater than 500 nucleotides. LncRNAs are involved in nearly every aspect of cellular physiology, playing fundamental regulatory roles both in normal cells and in disease. As result, they are functionally linked to multiple human diseases, from cancer to autoimmune, inflammatory, and neurological disorders. Numerous human conditions and diseases stem from gene-environment interactions; in this regard, a wealth of reports demonstrate that the intake of specific and essential nutrients, including vitamins, shapes our transcriptome, with corresponding impacts on health. Vitamins command a vast array of biological activities, acting as coenzymes, antioxidants, hormones, and regulating cellular proliferation and coagulation. Emerging evidence suggests that vitamins and lncRNAs are interconnected through several regulatory axes. This type of interaction is expected, since lncRNA has been implicated in sensing the environment in eukaryotes, conceptually similar to riboswitches and other RNAs that act as molecular sensors in prokaryotes. In this review, we summarize the peer-reviewed literature to date that has reported specific functional linkages between vitamins and lncRNAs, with an emphasis on mammalian models and humans, while providing a brief overview of the source, metabolism, and function of the vitamins most frequently investigated within the context of lncRNA molecular mechanisms, and discussing the published research findings that document specific connections between vitamins and lncRNAs., (© 2024. The Author(s).)

The Intelligent Transportation System (ITS) seeks to improve traffic flow to guarantee transportation safety. One of the ITS's fundamental tenets is identifying and classifying vehicles into various classes. Although the issues related to small size, variety of forms, and similarity in visual appearance of the vehicles, as well as the influence of the weather on the video and image quality, make it challenging to categorize vehicles using unmanned aerial vehicles (UAV); they are becoming more popular in computer vision-related applications. Traffic accidents are now a serious public health concern that must be addressed in the Kurdistan Region of Iraq. An automatic vehicle detection and classification system can be considered one of the remedies to solve this issue. This paper presents a dataset of 2,160 images of vehicles on the roads in the Iraqi Kurdistan Region to address the issue of the absence of such a dataset. The images in the proposed collection were taken with a Mavic Air 2 drone in the Iraqi cities of Sulaymaniyah and Erbil. The images are categorized into five classes: bus, truck, taxi, personal car, and motorcycle. Data gathering considered diverse circumstances, multiple vehicle sizes, weather and lighting conditions, and massive camera movements. Pre-processing and data augmentation methods were applied to the images in our proposed dataset, including auto-orient, brightness, hue, and noise algorithm, which can be used to build an efficient deep learning (DL) model. After applying these augmentation techniques for the car, taxi, truck, motorcycle, and bus classes, the number of images was increased to 5,353, 1,500, 1,192, 282, and 176, respectively., (© 2024 The Authors. Published by Elsevier Inc.)

Aims: To evaluate the association between ideal cardiovascular health metrics (ICVHM) and incident low estimated glomerular filtration rate (eGFR) among the Iranian population., Methods: The study population included 6927 Iranian adults aged 20-65 years (2942 male) without prevalent low eGFR [i.e., eGFR < 60 ml/min/1.73 m2] and free of cardiovascular disease. The ICVHM was defined according to the 2010 American Heart Association. The multivariable Cox proportional hazards regression analysis was used to calculate the hazard ratios (HRs) of ICVHM both as continuous and categorical variables., Results: Over the median of 12.1 years of follow-up, we found 1259 incident cases of low eGFR among the study population. In this population, ideal and intermediate categories of body mass index (BMI) and blood pressure (BP) and only the ideal category of fasting plasma glucose (FPG) significantly decreased the risk of developing low eGFR; the corresponding HRs and (95% confidence intervals) were (0.87, 0.77-0.99), (0.84, 0.76-0.99), (0.79, 0.68-0.93), (0.70, 0.60-0.83) and (0.76, 0.64-0.91). Also, one additional ICVHM was associated with a reduced risk of low eGFR for the global (0.92, 0.88-0.97) and biological cardiovascular health (0.88, 0.82-0.93) in these participants. A sensitivity analysis using the interval-censoring approach demonstrated that our method is robust, and results remained essentially unchanged. In a subgroup population with dietary data (n = 2285), we did not find the beneficial impact of having intermediate/ideal categories of nutrition status compared to its poor one on incident low eGFR., Conclusion: We found a strong inverse association between having higher global ICVHM with incident low eGFR among the non-elderly Iranian population; the issue is mainly attributable to normal BP, BMI, and FPG levels., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alizadeh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Uninterrupted microscopic observation and real-time imaging of cell behavior during exposure to the stimulus, for example, electric and/or magnetic fields, especially for periods of several days, has been a challenge in experimental bioelectromagnetics due to a lack of proper gas/temperature conditions outside the incubator. Conventional mini-incubators might suffer from stray fields produced by heating elements. We report an in vitro electric and magnetic fields (EMF) exposure system embedded inside a novel under-the-microscope mini-CO 2 -incubator with a unique design to avoid electromagnetic interference from the heating and circulation functions while ensuring the requisite temperature. A unique, reconfigurable array of electrodes and/or coils excited by calculated current distributions among array elements is designed to provide excellent field uniformity and controllable linear or circular polarization (even at very low frequencies) of the EMF within the cell culture. Using standard biochemical assays, long-term cell viability has been verified and compared with a conventional incubator. Cell orientation/migration in three-dimensional culture made of collagen-hydrogels has been successfully observed in vitro, in long-term, and in real-time under the influence of DC electric fields with the device., (© 2023 Bioelectromagnetics Society.)

Purpose: This study aimed to investigate binge-watching behavior and addiction among a sample of 446 Chinese college students and assess its consequences for mental health, with a particular focus on feelings of loneliness, anxiety, and depression., Participants and Methods: We conducted an online survey to gather data, examining participants' binge-watching habits and preferred platforms. We also utilized regression analysis to assess the impact of binge-watching addiction on mental health, exploring the associations between binge-watching addiction and feelings of loneliness, anxiety, and depression., Results: Our findings revealed that the Chinese college students in our study typically defined binge-watching sessions as lasting approximately 7.22 hours, with an average of 10.83 episodes. Regarding the self-assessment of binge-watching, the average duration of participants was 5.76 hours, and the average number of episodes was 7.42. Tencent Video, iQIYI, and Bilibili emerged as the dominant platforms for binge-watching among the respondents. Regression analysis demonstrated a significant link between binge-watching addiction and mental health, with positive associations observed between binge-watching addiction and increased feelings of loneliness, anxiety, and depression., Conclusion: The results of this study reinforce previous findings regarding the detrimental effects of excessive media consumption on mental well-being. Moreover, they provide valuable insights into the global prevalence of binge-watching and its impact on the psychological health of young adults in the digital age, emphasizing the need for proactive measures to address this issue., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Yu and Alizadeh.)

Background: The ability to attribute mental states to others is called theory of mind (ToM) and is a substantial component of social cognition. This ability is abnormally developed in individuals with autism spectrum disorder (ASD). Several studies over the past decade have identified the oxytocin receptor gene (OXTR) and its variants as promising components for explaining the molecular mechanisms underlying Theory of Mind (ToM). The main aim of this study is to examine the association between rs2268498 and rs53576, two functional single nucleotide polymorphisms (SNPs), and verbal and non-verbal ToM in children and adolescents with ASD and a group of typically developing youth., Methods: The study involved 44 children and adolescents with high-functioning ASD aged 8 to 18 years old and 44 TD individuals who were matched on age and sex. In all participants, blood samples were collected and rs2268498 and rs53576 were genotyped. Happe's Strange Stories test and the moving shapes paradigm were used to measure verbal and non-verbal ToM in all participants., Results: The results of permutation tests and logistic regression suggested that in TD group, rs2268498 AA carriers showed significant higher scores in variables representing verbal ToM (ToM stories and appropriateness score) whereas, in ASD group, rs53576 AA carriers exhibited significant better performance in parameters related to non-verbal ToM (ToM general rule and intentionality score). The results of hierarchical clustering in both groups support the findings by distinguishing between language-related and language-independent aspects of ToM., Conclusions: In the present study, we examined the association between rs2268498 and rs53576 and social functioning in individuals with ASD and TD group. We found preliminary evidence that rs2268498 and rs53576 are associated with ToM related abilities in healthy individuals as well as in autistic individuals. Accordingly, rs2268498 and rs53576 may play an important role in predicting ToM capabilities. It will be necessary to conduct further research to address the association of genetic variants with a deficit in ToM in individuals with ASD., (© 2023. The Author(s).)

Intra-individual behavioral variability is significantly heightened by aging or neuropsychological disorders, however it is unknown which brain regions are causally linked to such variabilities. We examine response time (RT) variability in 21 macaque monkeys performing a rule-guided decision-making task. In monkeys with selective-bilateral lesions in the anterior cingulate cortex (ACC) or in the dorsolateral prefrontal cortex, cognitive flexibility is impaired, but the RT variability is significantly diminished. Bilateral lesions within the frontopolar cortex or within the mid-dorsolateral prefrontal cortex, has no significant effect on cognitive flexibility or RT variability. In monkeys with lesions in the posterior cingulate cortex, the RT variability significantly increases without any deficit in cognitive flexibility. The effect of lesions in the orbitofrontal cortex (OFC) is unique in that it leads to deficits in cognitive flexibility and a significant increase in RT variability. Our findings indicate remarkable dissociations in contribution of frontal cortical regions to behavioral variability. They suggest that the altered variability in OFC-lesioned monkeys is related to deficits in assessing and accumulating evidence to inform a rule-guided decision, whereas in ACC-lesioned monkeys it results from a non-adaptive decrease in decision threshold and consequently immature impulsive responses., (© 2024. The Author(s).)

Candida albicans readily develops resistance to fluconazole. Magnetic iron oxide nanoparticles (denoted as MION) and antimicrobial photodynamic therapy are attracting attention as therapeutic agents. This study aims to investigate the inhibitory efficacy of MION alone and combined with visible light against C. albicans and expression analysis of hyphal wall protein 1 (HWP1) and agglutinin-like sequence 1 (ALS1) genes in C. albicans. Antifungal susceptibility testing, photodynamic activity assay, reactive oxygen species (ROS) production assay and gene expression analysis were determined in C. albicans treated with MION alone and combined with visible light. MION at 1 × minimum inhibitory concentration (MIC) level (500 μg/mL) exhibited antifungal activity against C. albicans isolates. Further, 1 × MIC levels of MION alone and combined with visible light displayed remarkable fungicidal effects at 24 and 48 h after treatment. The MION combined with visible light caused the highest levels of ROS production by all C. albicans isolates. The relative RT-PCR data showed significant downregulation of HWP1 and ALS1 genes which are the key virulence genes in C. albicans. Differences in gene expression of  HWP1 and ALS1 were more significant in MION combined with visible light treatments than MION alone. Our study sheds a novel light on facile development of effective treatment of C. albicans especially fluconazole-resistant C. albicans infections. The hyphae-specific genes HWP1 and ALS1 could be probable molecular targets for MION alone and combined with visible light in C. albicans., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Relationships between social drivers of health (SDoH) and pediatric health outcomes are highly complex with substantial inconsistencies in studies examining SDoH and extracorporeal membrane oxygenation (ECMO) outcomes. To add to this literature with emerging novel SDoH measures, and to address calls for institutional accountability, we examined associations between SDoH and pediatric ECMO outcomes., Methods: This single-center retrospective cohort study included children (<18 years) supported on ECMO (2012-2021). SDoH included Child Opportunity Index (COI), race, ethnicity, payer, interpreter requirement, urbanicity, and travel-time to hospital. COI is a multidimensional estimation of SDoH incorporating traditional (eg, income) and novel (eg, healthy food access) neighborhood attributes ([range 0-100] higher indicates healthier child development). Outcomes included in-hospital mortality, ECMO run duration, and length of stay (LOS)., Results: 540 children on ECMO (96%) had a calculable COI. In-hospital mortality was 44% with median run duration of 125 hours and ICU LOS 29 days. Overall, 334 (62%) had cardiac disease, 92 (17%) neonatal respiratory failure, 93 (17%) pediatric respiratory failure, and 21 (4%) sepsis. Median COI was 64 (interquartile range 32-81), 323 (60%) had public insurance, 174 (34%) were from underrepresented racial groups, 57 (11%) required interpreters, 270 (54%) had urban residence, and median travel-time was 89 minutes. SDoH including COI were not statistically associated with outcomes in univariate or multivariate analysis., Conclusions: We observed no significant difference in pediatric ECMO outcomes according to SDoH. Further research is warranted to better understand drivers of inequitable health outcomes in children, and potential protective mechanisms., (Copyright © 2023 by the American Academy of Pediatrics.)

Chemotherapy has been widely acknowledged as a primary approach for cancer treatment. However, the administration of chemotherapy agents is often limited by their adverse effects that result from an inability to distinguish between healthy and malignant cells. As such, utilising nanocarriers in targeted drug delivery can significantly reduce these side effects while enhancing therapeutic efficacy. Herein, we developed copper sulphide nanoparticles (CuSNPs) loaded with epirubicin (Epi) coated by polyarginine and 5TR1 aptamer (CEPA) to target mucin-1 which is overexpressed on various types of cancer cells. MTT results revealed that CEPA significantly induced cytotoxicity of the drug in desired cell lines (C26 and MCF-7, mucin + ) compared to CEPA-treated CHO cells (non-target, mucin - ), verifying the targeting ability of CEPA complex. The obtained results from both flow cytometry analysis and cell imaging demonstrated that CEPA complex had successful internalisation in both target cell lines but no internalisation in CHO cell line. The result of in vivo assay showed more tumour inhibition and more accumulation in tumour tissue for CEPA complex in comparison to free Epi. To conclude, the CEPA complex has demonstrated superior efficacy and fewer adverse reactions compared to Epi. This indicates a promising and effective strategy for treating cancer.

Generating animal models can explore the role of new candidate genes in causing diseases and the pathogenicity of a specific mutation in the underlying genes. These animals can be used to identify new pharmaceutical or genetic therapeutic methods. In the present experiment, we developed a rpe65a knock out (KO) zebrafish as a retinitis pigmentosa (RP) disease model. Using the CRISPR/Cas9 system, the rpe65a gene was KO in zebrafish. Two specific single-guide RNAs (sgRNAs) were designed for the zebrafish rpe65a gene. SgRNAs were cloned into the DR274 plasmid and synthesized using in vitro transcription method. The efficiency of Ribonucleoprotein (synthesized sgRNA and recombinant Cas9) was evaluated by in vitro digestion experiment. Ribonucleoprotein complexes were microinjected into one to four-celled eggs of the TU zebrafish strain. The effectiveness of sgRNAs in KO the target gene was determined using the Heteroduplex mobility assay (HMA) and Sanger sequencing. Online software was used to determine the percent of mosaicism in the sequenced samples. By examining the sequences of the larvae that showed a mobility shift in the HMA method, the presence of indels in the binding region of sgRNAs was confirmed, so the zebrafish model for RP disease established. Zebrafish is an ideal animal model for the functional study of various diseases involving different genes and mutations and used for evaluating different therapeutic approaches in human diseases. This study presents the production of rpe65a gene KO zebrafish models using CRISPR/Cas9 technology. This model can be used in RP pathophysiology studies and preclinical gene therapy experiments., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Monitoring progress towards the WHO global target to eliminate hepatitis C virus (HCV) infection by 2030, entails reliable prevalence estimates for HCV infection in different populations. Little is known about the global burden of HCV infection in pregnant women. Here, for the first time to our knowledge, we estimated the global and regional seroprevalence of HCV antibody (Ab) and determinants in pregnant women., Methods: In this systematic review and meta-analysis study, we searched PubMed/MEDLINE, Web of Science, Embase, Scopus, and SciELO databases for peer-reviewed observational studies between January 1, 2000 and April 1, 2023, without language or geographical restrictions. Pooled global seroprevalence (and 95% confidence interval, CI) were estimated using random-effects meta-analysis and seroprevalences were categorised according to World Health Organization regions and subregions, publishing year, countries' income and human development index (HDI) levels. We used sensitivity analysis to assess the effect of four large sample size studies on pooled global prevalence through the "leave-one-out" method. We also investigated the association of potential risk factors with HCV seropositivity in pregnant women by subgroup and meta-regression analyses. The Protocol was registered in PROSPERO CRD42023423259., Findings: We included 192 eligible studies (208 datasets), with data for 148,509,760 pregnant women from 53 countries. The global seroprevalence of HCV Ab in pregnant women was 1.80% (95% CI, 1.72-1.89%) and 3.29% (3.01-3.57%) in overall and sensitivity analyses, respectively. The seroprevalence was highest in the Eastern Mediterranean region (6.21%, 4.39-8.29%) and lowest in the Western Pacific region (0.75%, 0.38-1.22%). Subgroup analysis indicated that the seroprevalence of HCV Ab among pregnant women was significantly higher for those with opioid use disorder (51.94%, 95% CI: 37.32-66.39) and HIV infection (4.34%, 95% CI: 2.21-7.06%) than for the general population of pregnant women (1.08%, 95% CI: 1.02-1.15%), as confirmed by multivariable meta-regression (p < 0.001). A significant decreasing trend was observed with increasing human development index levels. Other important risk factors for HCV seropositivity included older age, lower educational levels, poly sexual activity, history of blood transfusion, hospitalization, surgery, abortion and sexual transmitted diseases, having scarification/tattoo or piercing, and testing hepatitis B positive., Interpretation: This meta-analysis showed relatively high burden of exposure to HCV infection (2.2-5.3 million) in pregnant women globally. However, due to substantial heterogeneity between studies, our estimates might be different than the true seroprevalence. Our findings highlighted the need to expand HCV screening for women of reproductive age or during pregnancy, particularly in countries with high prevalence; as well as for more studies that assess safety of existing therapeutic drugs during pregnancy or potentially support development of drugs for pregnant women., Funding: There was no funding source for this study., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Purpose: Major histocompatibility complex class II (MHC-II) deficiency is a rare inborn error of immunity (IEI). Impaired antigen presentation to CD4 + T cells results in combined immunodeficiency (CID). Patients typically present with severe respiratory and gastrointestinal tract infections at early ages. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy., Methods: We describe the clinical, immunologic, and genetic features of eighteen unrelated Iranian patients with MHC-II deficiency., Results: Consanguinity was present in all affected families. The median age at the initial presentation was 5.5 months (range 7 days to 18 years). The main symptoms included failure to thrive, persistent diarrhea, and pneumonia. Autoimmune and neurologic features were also documented in about one-third of the patients, respectively. Thirteen patients carried RFXANK gene mutations, two carried RFX5 gene mutations, and three carried a RFXAP gene mutation. Six patients shared the same RFXANK founder mutation (c.162delG); limited to the Iranian population and dated to approximately 1296 years ago. Four of the patients underwent HSCT; three of them are alive. On the other hand, nine of the fourteen patients who did not undergo HSCT had a poor prognosis and died., Conclusion: MHC-II deficiency is not rare in Iran, with a high rate of consanguinity. It should be considered in the differential diagnosis of CID at any age. With the limited access to HSCT and its variable results in MHC-II deficiency, implementing genetic counseling and family planning for the affected families are mandatory. We are better determined to study the c.162delG RFXANK heterozygous mutation frequency in the Iranian population., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Diabetes mellitus (DM) is a common metabolic disease characterized by high blood sugar levels. It is well known that men with diabetes frequently experience reproductive disorders and sexual dysfunction. In fact, sperm quality has a significant effect on fertilization success and embryo development. The current study aimed to investigate the effect of Stevia rebaudiana hydroalcoholic extract on serum testosterone levels, sperm parameters, in vitro fertilization (IVF) success, and in vitro embryonic developmental potential to reach the blastocyst stage in a streptozotocin (STZ)-induced mouse model of diabetes. In this research, 30 male mice were distributed randomly into control, diabetic (streptozotocin 150 mg/kg) and diabetic + Stevia (400 mg/kg) groups. The results revealed a decrease in body and testis weight and elevated blood fasting blood sugar (FBS) levels in the diabetic group, compared with the control. However, Stevia treatment significantly increased body and testis weight, while serum FBS levels were decreased compared with the diabetic group. In addition, Stevia significantly increased blood testosterone levels compared with the diabetic group. Moreover, sperm parameters were improved considerably by Stevia treatment compared with the diabetic group. Furthermore, Stevia administration significantly promoted IVF success rate and in vitro development of fertilized oocytes compared with the diabetic group. In summary, our data indicated that Stevia enhanced sperm parameters, IVF success, and in vitro embryonic developmental competency in diabetic mice, probably because of its antioxidant effects. Therefore, Stevia could ameliorate sperm parameters that, in turn, increase fertilization outcomes in experimental-induced diabetes.

Discovery and validation of new, reliable diagnostic and predictive biomarkers for schizophrenia (SCZ) are an ongoing effort. Here, we assessed the mRNA expression and DNA methylation of the TCF4, MBP, and EGR1 genes in the blood of patients with SCZ and evaluated their relationships to psychopathology and cognitive impairments. Quantitative real-time PCR and quantitative methylation-specific PCR methods were used to assess the expression level and promoter DNA methylation status of these genes in 70 drug-free SCZ patients and 72 healthy controls. The correlation of molecular changes with psychopathology and cognitive performance of participants was evaluated. We observed downregulation of TCF4 and upregulation of MBP mRNA levels in SCZ cases, relative to controls in our study. DNA methylation status at the promoter region of TCF4 demonstrated an altered pattern in SCZ as well. Additionally, TCF4 mRNA levels were inversely correlated with PANSS and Stroop total errors and positively correlated with WAIS total score and working memory, consistent with previous studies by our group. In contrast, MBP mRNA level was significantly positively correlated with PANSS and Stroop total errors and inversely correlated with WAIS total score and working memory. These epigenetic and expression signatures can help to assemble a peripheral biomarker-based diagnostic panel for SCZ., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pseudomonas aeruginosa is a human bacterial pathogen causing devastating diseases and equipped with various virulence factors like biofilm formation. Common antibiotic treatment has limited efficacy for the P. aeruginosa present in biofilms because of the increased resistance. In this study, we focused our attention on the antibacterial and anti-biofilm activities of various microbial synthesized silver (nano-Ag) and magnetic iron oxide (nano-Fe3O4) nanoparticles against clinical isolates of P. aeruginosa that displayed ceftazidime resistance. The nano-Ag and nano-Fe3O4 represented great antibacterial properties. Nano-Ag and nano-Fe3O4 exhibited a reduction in the biofilm formation by P. aeruginosa reference strain as determined by crystal violet and XTT assays and light microscopy method. Among all, nano-Ag-2 and 7 owing to inherent attributes and mechanisms of resistance in the bacterial biofilm, exhibited anti-biofilm efficacy against ceftazidime resistance clinical isolate of P. aeruginosa. Moreover, nano-Ag and nano-Fe3O4 changed the relative expression of biofilm-associated genes, PELA and PSLA in a concentration dependent manner by P. aeruginosa reference strain. As revealed by qRT-PCR, the expression levels of biofilm-associated genes were downregulated in P. aeruginosa biofilms treated with nano-Ag, while selected biofilm-associated genes were low expressed under treated with nano-Fe3O4. Results of the study demonstrate the potential of microbial synthesized nano-Ag-2 and 7 to act as anti-biofilm agents against ceftazidime resistance clinical isolate of P. aeruginosa. Molecular targeting of biofilm-associated genes by nano-Ag and nano-Fe3O4 may be candidate for new therapeutics against P. aeruginosa diseases.

mRNA-lipid nanoparticle (mRNA-LNP) vaccines have proved their efficacy, versatility and unprecedented manufacturing speed during the COVID-19 pandemic. Here we report on the physicochemical properties, thermostability, immunogenicity, and protective efficacy of the nucleoside-modified mRNA-LNP vaccine candidate Iribovax® (also called SNEG2c). Injection of BALB/c mice, rabbits and nonhuman primates with two doses of SNEG2c induced production of high-titers of SARS-CoV-2 spike-specific and receptor-binding domain (RBD)-neutralizing antibodies in immunized animals. In addition to the strong humoral response, SNEG2c elicited substantial Th1-biased T-cell response. Sera from rhesus macaques immunized with a low dose of the vaccine showed robust spike-specific antibody titers 3-24× as high as those in convalescent sera from a panel of COVID-19 patients and 50% virus neutralization geometric mean titer of 1024 against SARS-CoV-2. Strikingly, immunization with SNEG2c completely cleared infectious SARS-CoV-2 from the upper and lower respiratory tracts of challenged macaques and protected them from viral-induced lung and trachea lesions. In contrast, the non-vaccinated macaques developed moderate to severe pulmonary pathology after the viral challenge. We present the results of repeat-dose and local tolerance toxicity and thermostability studies showing how the physicochemical properties of the mRNA-LNPs change over time and demonstrating that SNEG2 is safe, well tolerated and stable for long-term. These results support the planned human trials of SNEG2c., Competing Interests: Declaration of Competing Interest The authors declare that M.R.J and S.M.J are co-inventors on pending patent applications related to the SNEG2c mRNA-LNP vaccine. The other authors declare no competing interests to this work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The prevalence of obesity in children with congenital heart disease (CHD) is greater than 25%, putting these patients at-risk for increased surgical morbidity and mortality. Our goal was to determine the association between CHD complexity, sociodemographic factors, and obesity. Our hypothesis was that among CHD patients, the odds of obesity would be highest in older children with simple CHD, and in all children with a lower socioeconomic status. We conducted a retrospective cohort study, reviewing electronic medical records of children aged 2-17 years from over 50 outpatient pediatric clinics in Houston, TX. Children were classified as simple or moderate/complex CHD, and obesity was defined by BMI ≥ 95th percentile for age and sex. Logistic regression was used to determine the association between sociodemographic factors and CHD complexity with obesity. We identified 648 CHD and 369,776 non-CHD patients. Children with simple CHD had a similar odds of obesity as non-CHD children. Children with CHD had a higher prevalence of obesity if they were older, male, Black, Hispanic, and publicly insured. Children with moderate/complex CHD had lower odds of obesity [OR 0.24 (95% CI 0.07-0.73)], however their predicted probability of obesity approached that of the general population as they aged. Additionally, there was an incremental relationship with poverty and obesity [1.01 (1.01-1.01)]. Awareness of which patients with CHD are at highest risk of obesity may help in targeting interventions to assist at-risk patients maintain a healthy lifestyle., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Tablet manufacturing development is costly, laborious, and time-consuming. Technologies related to artificial intelligence like ,predictive model ,can be used in the control process to facilitate and accelerate the tablet manufacturing process. predictive models have become popular recently. However, predictive models need a comprehensive dataset of related data in the field, due to the lack of a dataset of tablet formulations, the aim of this study is to aggregate and integrate fast disintegration tablet's formulation into a comprehensive dataset., Data Description: The search strategy has been prepared between the years of 2010 to 2020, consisting of the keyword's 'formulation' ,'disintegrating' and 'Tablet', as well as their synonyms. By searching four databases, 1503 articles were retrieved, from these articles only 232 articles met all of the study's criteria. By reviewing 232 articles, 1982 formulations have been extracted, afterward pre-processing and cleaning data, contain steps of unifying the name and units, removing inappropriate formulations by an expert, and finally, data tidying was done on data. The developed dataset contains valuable information from various FDT's formulations, which can be used in pharmaceutical studies that are critical to the discovery and development of new drugs. this method can be applied to aggregate datasets from the other dosage forms., (© 2023. The Author(s).)