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Abstract Pathogenic fungi employ numerous strategies to colonize plants, infect them, reduce crop yield and quality, and cause significant losses in agricultural production. The increasing use of chemical pesticides has led to various ecological and environmental issues, including the emergence of resistant weeds, soil compaction, and water pollution, all negatively impacting agricultural sustainability. Additionally, the extensive development of synthetic fungicides has adverse effects on animal and human health, prompting the exploration of alternative approaches and green strategies for phytopathogen control. Microorganisms living in sponges represent a promising source of novel bioactive secondary metabolites, potentially useful in developing new nematicidal and antimicrobial agents. This study focuses on extracting bioactive compounds from endosymbiotic bacteria associated with the marine sponge Hyrtios erect sp. (collected from NIOF Station, Hurghada, Red Sea, Egypt) using various organic solvents. Bacillus sp. was isolated and identified through 16 S rRNA gene sequencing. The biocidal activity of Bacillus gotheilii MSB1 extracts was screened against plant pathogenic bacteria, fungi, and nematodes. The n-butanol extract showed significant potential as a biological fungicide against Alternaria alternata and Fusarium oxysporum. Both n-hexane and ethyl acetate extracts exhibited negative impacts against the plant pathogenic bacteria Erwinia carotovora and Ralstonia solanacearum, whereas the n-butanol extract had a positive effect. Regarding nematicidal activity, ethyl acetate and n-butanol extracts demonstrated in-vitro activity against the root-knot nematode Meloidogyne incognita, which causes serious vegetable crop diseases, but the n-hexane extract showed no positive effects. The findings suggest that bioactive compounds from endosymbiotic bacteria associated with marine sponges, particularly B. gotheilii MSB1, hold significant potential as alternative biological control agents against plant pathogens. The n-butanol extract, in particular, displayed promising biocidal activities against various plant pathogenic fungi, bacteria, and nematodes. These results support further exploration and development of such bioactive compounds as sustainable, environmentally friendly alternatives to synthetic pesticides and fungicides in agricultural practices.

Abstract We identified two homozygous truncating variants in GON4L [NM_001282860.2:c.62_63del, p.(Gln21Argfs*12) and c.5517+1G>A] in two unrelated families who presented prenatal-onset growth impairment, microcephaly, characteristic face, situs inversus, and developmental delay. The frameshift variant is predicted to invoke nonsense-mediated mRNA decay of all five known GON4L isoforms resulting in the complete loss of GON4L function. The splice site variant located at a region specific to the longer isoforms; therefore, defects of long GON4L isoforms may explain the phenotypes observed in the three patients. Knockdown of Gon4l in rat PC12 cells suppressed neurite outgrowth in vitro. gon4lb knockdown and knockout zebrafish successfully recapitulated the patients’ phenotypes including craniofacial abnormalities. We also observed situs inversus in gon4lb-knockout zebrafish embryo. To our knowledge, the relationship between craniofacial abnormalities or situs inversus and gon4lb has not been reported before. Thus, our data provide evidence that GON4L is involved in craniofacial and left-right patterning during development.

Plasmodium falciparum infection threatens military populations deployed to highly malaria-endemic regions, such as Peruvian Army peacekeepers deployed to Central African Republic. During deployment, malaria cases were identified by microscopy and rapid diagnostic tests. After deployment, we performed malaria diagnosis by malachite green loop-mediated isothermal amplification and photo-induced electron transfer PCR assays. We used ELISA to test for P. falciparum C-terminal 19-kDa region merozoite surface protein 1–specific IgG from 97 peacekeepers. Malaria prevalence during deployment was 33.33% and we detected 4 cases after deployment: P. falciparum (n = 2), P. ovale (n = 1), and Plasmodium spp. (n = 1). IgG surveillance showed a seroprevalence of 31.96% in peacekeepers, who had a high P. falciparum exposure during deployment. Our findings reinforce the necessity of active surveillance in military populations to reduce the risk for introduction of new Plasmodium species and strains into the Americas from malaria-endemic areas.

Abstract Knee osteoarthritis (KOA) is an important cause of disability in the world and it denotes a public health defiance of the upcoming years. Aim To examine the connection between ADAMTS14 gene rs4747096 polymorphism and KOA and to assess risk factors associated with KOA. Methods A case control study was conducted on 158 patients with KOA and 120 controls with comparable age and sex randomly recruited from National Research Centre employees. All participants were subjected to full history taking, assessment of KOA severity using WOMAC scoring system, and thorough clinical examination. Blood sample was collected for detection of ADAMTS14/rs4747096 gene polymorphism. Results The frequency of ADAMTS14 gene rs4747096 genotypes among patients with KOA was 73.5% for AA, 25.7% for AG, and 0.7% for GG compared to controls 963%, 31.3%, and 5.6% respectively and the frequency of alleles among patients was 86.4% for A and 78.7% for G compared to controls (78.7% and 21.3% respectively, P

Abstract Background It has been proposed that prolonged use of anti-inflammatory and anti-fibrotic drugs diminish the probability of development of lung fibrosis. Prolonged low-dose corticosteroid may prevent remodeling of the lung in survivors. Pirfenidone and colchicine may exhibit anti-fibrotic and anti-inflammatory properties as well. Methods This retrospective observational study was conducted at post COVID-19 clinic, Mansoura University Hospitals, during the period between October 2020 and March 2022. This study included 104 patients who had COVID-19 pneumonia confirmed either by RT-PCR or radiologically by CT scan and divided into 3 groups; group A (corticosteroids only) included 33 (31.7%) patients, group B (corticosteroids and colchicine) included 56 (53.8%) patients, and group C (corticosteroids, colchicine, and pirfenidone) included 15 (14.4%) patients. All patients were assessed during follow-up visits in post COVID-19 clinic 1 and 3 months after discharge by evaluation of resting SpO2, spirometry, and radiological assessment. Patients’ data during hospitalization was collected from hospital electronic systems. Results There was non-statistically significant improvement in FEV1 in group A while there was statistically significant improvement in FEV1 in groups B and C (P value = 0.002 and 0.041, respectively) 1 month and 3 months after discharge. Group B exhibited more statistically significant improvement in FVC as well compared to group C (P value = 0.003 and 0.025, respectively) while group A showed non-statistically significant improvement in FVC. There was a statistically significant decrease in CT severity score in all the groups during follow-up with P value

Abstract Ageing is the accumulation of changes and decline of function of organisms over time. The concept and biomarkers of biological age have been established, notably DNA methylation-based clocks. The emergence of single-cell DNA methylation profiling methods opens the possibility of studying the biological age of individual cells. Here, we generate a large single-cell DNA methylation and transcriptome dataset from mouse peripheral blood samples, spanning a broad range of ages. The number of genes expressed increases with age, but gene-specific changes are small. We next develop scEpiAge, a single-cell DNA methylation age predictor, which can accurately predict age in (very sparse) publicly available datasets, and also in single cells. DNA methylation age distribution is wider than technically expected, indicating epigenetic age heterogeneity and functional differences. Our work provides a foundation for single-cell and sparse data epigenetic age predictors, validates their functionality and highlights epigenetic heterogeneity during ageing.

Abstract Background Several antibiotics are partially metabolized by patients after administration and end up in municipal sewage systems. The fate of biodegradation in aquatic environments and the role of biodegradation in the development of bacterial resistance are poorly understood. Thus, as a crucial step in an environmental risk assessment, the biodegradability of many therapeutically significant antibiotics was investigated. Results A marine halophilic bacteria that degrades penicillin G (PEN-G) was isolated and identified based on morphology, physio-biochemical characteristics, and 16S rDNA sequences as Bacillus pseudomycoides AH1 (accession no. MF037698). The effects of various concentrations of PEN-G and carbon and nitrogen sources on the biotransformation ability at 30°C and pH 7.0 were evaluated. Cells grown in medium supplemented with glucose as an additional carbon source and yeast extract as a nitrogen source exhibited maximal PEN-G biotransformation efficiency and rate (71.678% ±1.28 and 2.99 mg/h, respectively). The culture conditions for B. pseudomycoides AH1 cells were optimized using a Plackett–Burman design (PBD). Six key determinants (p < 0.05) significantly affected the process outcome, as deduced by regression analysis of the PBD data, and modified MSM broth achieved PEN-G biotransformation efficiency (100%) under aerobic shaking conditions at 35°C, irrespective of HPLC analysis. Additionally, the present investigation could strongly support the application of immobilization approaches for the removal of PEN-G-contaminated environmental sites. Conclusion To the best of the authors’ knowledge, this is the first detailed study on the efficient biotransformation of PEN-G by an alginate-bacteria system as a simple, green, and inexpensive process, as well as a promising method.

Abstract This research primarily focuses on the strength indicators of the bearing structures of ADM-1 special self-propelled rolling stock. The special self-propelled rolling stock used by Uzbek railroads reaching the end of their functional life is a pertinent problem as Uzbekistan's railway system is growing rapidly, but there is a lack of enough funds to buy new special self-propelled rolling stock. Hence, it is vital to fix the issues with ADM-1 special self-propelled rolling stock by overhauling them. At the outset, the researchers divided the frame of a special a self-propelled rolling stock into multiple sections. Subsequently, these individual sections were analyzed closely to spot out issues. The precise location of the fatigue defect occurrence on the longitudinal beams was determined by the analysis of the individual sections of the special self-propelled rolling stock. During the motor carriage's modernization, which is an approach to extend the service life and improve the durability of special self-propelled rolling stock, this analysis helped in pinpointing exactly the location on the frame where the stress measurements had to be calculated. Pre- and post-modernization calculations were carried out on the vehicle to determine the optimal placement of the reinforcing plates. Additionally, normative calculations were also conducted and a new design mode distinct from the repair loads was implemented. The computation results revealed that the fatigue resistance reserve coefficient and service life value prior to the bearing structure’s modernization in section 1 were below the required values of n = 1.5 and 1.49, respectively. All the sections of the load-bearing structure fulfilled the fatigue resistance reserve coefficient standards after the modernization. The computational model of the motor carriage's structural strength was created in the ANSYS Workbench platform. This research intends to enhance the strength determination procedures and provides recommendations for design and restoration of modern structures of special self-propelled rolling stock.

Archaic admixture has had a substantial impact on human evolution with multiple events across different clades, including from extinct hominins such as Neanderthals and Denisovans into modern humans. In great apes, archaic admixture has been identified in chimpanzees and bonobos but the possibility of such events has not been explored in other species. Here, we address this question using high-coverage whole-genome sequences from all four extant gorilla subspecies, including six newly sequenced eastern gorillas from previously unsampled geographic regions. Using approximate Bayesian computation with neural networks to model the demographic history of gorillas, we find a signature of admixture from an archaic 'ghost' lineage into the common ancestor of eastern gorillas but not western gorillas. We infer that up to 3% of the genome of these individuals is introgressed from an archaic lineage that diverged more than 3 million years ago from the common ancestor of all extant gorillas. This introgression event took place before the split of mountain and eastern lowland gorillas, probably more than 40 thousand years ago and may have influenced perception of bitter taste in eastern gorillas. When comparing the introgression landscapes of gorillas, humans and bonobos, we find a consistent depletion of introgressed fragments on the X chromosome across these species. However, depletion in protein-coding content is not detectable in eastern gorillas, possibly as a consequence of stronger genetic drift in this species.

Abstract Objectives With rapid advances in ultrasound‐guided procedures, there is an unmet need for echogenic phantoms with sufficient anatomical details for artificial intelligence and ultrasound‐guided device testing. We developed a method for creating neck phantoms for novel otolaryngology‐related device testing. To achieve accurate representation of the anatomy, we utilized CT scans and 3D printing technology to create customized agar molds, thus providing high‐fidelity yet cost‐effective tools. Methods Based on previous studies, the key components in our neck phantom include the cervical vertebrae, trachea, common carotid arteries, internal jugular veins, thyroid gland, and surrounding soft tissue. Open‐source image analysis software were employed to process CT data to generate high fidelity 3D models of the target structures. Resin molds were 3D printed and filled with various agar mixtures to mimic anatomical echogenicity. Results Following the method proposed, we successfully assembled the neck phantom which provided a detailed representation of the target structures. To evaluate the results, ultrasound data was collected on the phantom and living tissue and analyzed with ImageJ. We were able to demonstrate echogenicity comparable to that of living tissue. Conclusion The proposed method for building neck phantoms with detailed anatomical features offers a valuable, detailed, low‐cost tool for medical training and device testing in otolaryngology, particularly for novel devices that involve artificial intelligence (AI) guidance and robotic‐based needle insertion. Additional anatomical refinements and validation studies could further enhance the consistency and accuracy, thus paving the way for future advancements in ultrasound training and research, and ultimately benefiting patient care and safety.

Saiga antelope (Saiga tatarica) is a protected species in Kazakhstan. Little is known about the parasitofauna of these mammals. Therefore, the focus of this study was to evaluate the prevalence and species diversity of Eimeria spp. infection in the Volga-Ural Saiga antelope population. In June 2023, 104 Saiga antelope fecal samples collected from the district of Zhanibek, located in the province of West Kazakhstan were evaluated using microscopic and molecular techniques. Based on coprovoscopy results, Eimeria spp. Oocysts were present in 22 samples (21%). The four fecal samples containing the largest numbers of Eimeria spp. Oocysts per 10x field were selected for further genetic analysis. DNA extraction, nested PCR amplification, and sequencing were performed on 91 clones, with 80 clones forming a distinct clade and exhibiting genetic similarity to MT801034 Eimeria sp. Voucher HY3. These clones possibly represent an Eimeria specific to Saiga antelopes and gazelle that has previously been morphologically described as Eimeria elegans (Svanbaev, 1979), underscoring the importance of further research into parasitic infections in this protected species.

Background Asthma affects 300 million individuals worldwide. It is a serious global health problem affecting all age groups. The significance of eosinophilic inflammation in asthma is well established. Allergen immunotherapy (AIT) acts by increasing tolerance to specific antigens to which individuals demonstrate clinical sensitivity. Objectives Evaluate the efficacy and safety of sublingual immunotherapy (SLIT) versus subcutaneous immunotherapy (SCIT) as regards clinical response, total immunoglobulin E (IgE), and sputum eosinophil as well as adverse effects. Methods This randomized clinical trial included 100 patients with bronchial asthma who were randomly allocated into two groups: the SLIT group (n = 50) and the SCIT group (n = 50). Patients were given a full allergy history, symptoms, and medication scores; a skin prick test; total IgE for allergens, and a sputum eosinophil count. After the end of treatment, the efficacy, as well as side effects of both treatment arms, were evaluated at 6, 12, and 18 months. Results Both SLIT and SCIT were equally effective. Success rates have been demonstrated to be as high as 86–88%. There was a statistically significant decrease in symptom and medication scores, Total IgE levels, and sputum eosinophil results after treatment (P < 0.001). However, no difference was found between groups regarding the efficacy of treatment. SLIT was significantly safer than SCIT (P < 0.001). Conclusion Both treatment modalities were equally effective in treating asthma, but SLIT had a higher safety profile than SCIT.

Introduction: Obstructive sleep apnea syndrome (OSAS) is a clinical condition characterised by repeated periods of partial or full obstruction of airflow throughout sleep, with impairment of the quality of life and increased mortality with socioeconomic impacts. CPAP therapy is a simple and effective treatment option for OSAS patients. To overcome the clinical and prognostic limitations of AHI—as a sole index of OSAS—the Baveno classification was recently set out and introduced into clinical practice. This study aims to analyse the effect of the Baveno classification on the optimum CPAP titration pressure. Methods: A retrospective analysis of the records of sleep studies in two centres between 2018 and 2021 was carried out. Patients diagnosed with OSAS and recruited for CPAP titration were included. Based on the Baveno classification, the patients were categorised into four groups (A, B, C, and D). Results: Consequently, 700 patients were analysed and 427 patients were included. A significant positive correlation was detected between the CPAP optimum titration pressure and OSAS severity, neck circumference, the oxygen desaturation index (ODI), mean oxygen saturation, the AHI, the BMI, and cumulative sleep time when the SpO2 was p: p: 0.8, 0.4, 0.5, and 0.7, respectively). Conclusions: The Baveno classification is not useful in the prediction of CPAP optimum titration pressure. However, the ODI and neck circumference were significant independent predictors of a higher CPAP titration pressure.

In this study, several materials are presented as modifiers of the screen-printed carbon electrodes with the aim of developing new sensing platforms for the voltammetric analysis of drugs. Specifically, Clotiapine and Sulfamethoxazole were selected as models for antipsychotics and antibiotics, respectively. Different nanostructures were studied as modifiers, including both transition metals and carbon-based materials. Moreover, biochar and two metal-organic frameworks (MOFs) were tested as well. The NH2-MIL-125(Ti) MOF showed an 80% improvement in the analytical signal of Sulfamethoxazole, but it partially overlapped with an additional signal associated with the loss of the MOF ligand. For this reason, several immobilization strategies were tested, but none of them met the requirements for the development of a sensor for this analyte. Conversely, carbon nanotubes and the NH2-MIL-101(Fe) MOF were successfully applied for the analysis of Clotiapine in the medicine Etumine®, with RSD below 2% and relative errors that did not exceed 9% in any case, which demonstrates the precision and accuracy achieved with the tested modifications. Despite these promising results, it was not possible to lower the limits of detection and quantification, so in this sense further investigation must be performed to increase the sensitivity of the developed sensors.

Abstract Background Child disability has significant implications on their well-being and healthcare systems. Aim: This survey aimed to assess the magnitude of seven types of disability among Egyptian children aged 1

BackgroundStructural birth defects occur in approximately 3% of live births; most such defects lack defined genetic or environmental causes. Despite advances in surgical approaches, pharmacologic prevention remains largely out of reach.MethodsWe queried worldwide databases of 20,248 families that included children with neurodevelopmental disorders and that were enriched for parental consanguinity. Approximately one third of affected children in these families presented with structural birth defects or microcephaly. We performed exome or genome sequencing of samples obtained from the children, their parents, or both to identify genes with biallelic pathogenic or likely pathogenic mutations present in more than one family. After identifying disease-causing variants, we generated two mouse models, each with a pathogenic variant "knocked in," to study mechanisms and test candidate treatments. We administered a small-molecule Wnt agonist to pregnant animals and assessed their offspring.ResultsWe identified homozygous mutations in WLS, which encodes the Wnt ligand secretion mediator (also known as Wntless or WLS) in 10 affected persons from 5 unrelated families. (The Wnt ligand secretion mediator is essential for the secretion of all Wnt proteins.) Patients had multiorgan defects, including microcephaly and facial dysmorphism as well as foot syndactyly, renal agenesis, alopecia, iris coloboma, and heart defects. The mutations affected WLS protein stability and Wnt signaling. Knock-in mice showed tissue and cell vulnerability consistent with Wnt-signaling intensity and individual and collective functions of Wnts in embryogenesis. Administration of a pharmacologic Wnt agonist partially restored embryonic development.ConclusionsGenetic variations affecting a central Wnt regulator caused syndromic structural birth defects. Results from mouse models suggest that what we have named Zaki syndrome is a potentially preventable disorder. (Funded by the National Institutes of Health and others.).

Saiga antelope and Turkmenian kulans are considered critically endangered and near threatened, respectively, by the International Union for Conservation of Nature (IUCN). Due to these species’ fragile status, it is important to understand the pathogens infecting their remaining populations. A total of 496 faecal samples were collected from Ural saiga antelope in western Kazakhstan during June, September, and November of 2021 and May and August of 2022 and 149 faecal samples were collected from kulans in the Altyn-Emel nature reserve in south-eastern Kazakhstan from June to August of 2021. Additionally, endo- and ecto-parasites were collected from 17 saiga that were found deceased due to natural causes. Nine helminths (3 cestodes, 6 nematodes) and two protozoans were found in Ural saiga antelope. In addition to intestinal parasites, one case of cystic echinococcosis due to Echinococcus granulosus infection and one case of cerebral coenurosis due to Taenia multiceps infection was identified on necropsy. None of the collected ticks (all Hyalomma scupense) were found positive for Theileria annulate (enolase gene) or Babesia spp. (18 S ribosomal RNA gene) via PCR. Three intestinal parasites (Parascaris equorum, Strongylus sp., and Oxyuris equi) were found in kulans. All identified parasites, in both saiga and kulans, are also found in domesticated livestock, suggesting a need for better understanding of how parasites are maintained within and between regional wild and domestic ungulate populations.