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Calcium (Ca 2+ ) is a universal signaling cation with a prominent role as second messenger in many different plant processes, including sexual reproduction. However, there is much less knowledge about the involvement of Ca 2+ during in vitro embryogenesis processes. In this work we performed a study of Ca 2+ levels during the different stages of microspore embryogenesis in Brassica napus , with special attention to how Ca 2+ can influence the occurrence of different embryogenic structures with different embryogenic potential. We also performed a pharmacological study to modulate Ca 2+ homeostasis during different stages of the process, using a series of Ca 2+ -altering chemicals (BAPTA-AM, bepridil, chlorpromazine, cyclopiazonic acid, EGTA, inositol 1,4,5-trisphosphate, ionophore A23187, W-7). This study shows that Ca 2+ increase can be considered as an early marker of induction of microspore embryogenesis. Besides, Ca 2+ levels are highly dynamic during microspore embryogenesis, influencing the final embryo yield. Increase of either extracellular or intracellular Ca 2+ levels improves embryo yield without altering the proportion of highly embryogenic structures formed, which suggests that elevated Ca 2+ levels increase the amount of microspores reaching the minimum Ca 2+ threshold required for embryogenesis induction. Conversely, inhibition of Ca 2+ uptake or signaling results in reduced embryogenic response. This allows to modulate embryo yield within a functional range, with lower and upper Ca 2+ thresholds beyond which embryo yield is reduced. There seems to be a relationship between Ca 2+ levels and embryo differentiation., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 Calabuig-Serna, Mir, Sancho-Oviedo, Arjona-Mudarra and Seguí-Simarro.)

Introduction: Multiple Sclerosis care in the United Arab Emirates faces several barriers impacting patient outcomes and healthcare delivery. This study aims to identify and analyze these barriers from the perspective of neurologists., Methods: In February 2024, a survey was conducted targeting neurologists involved in Multiple Sclerosis management in Abu Dhabi. The survey included questions on demographics, regularly measured clinical variables, perceived barriers, and contributing factors. A total of 21 neurologists responded, and data were analyzed to identify prevalent issues and correlations., Results: Among the 21 respondents, 15 (71.4%) were male, and 15 (71.4%) were from private institutions. Most neurologists regularly advised on vitamin D level monitoring (16, 76.2%) and psychological support (15, 71.4%). Screening for disease-modifying treatment side effects, Expanded Disability Status Scale assessments, and magnetic resonance imaging comparisons were practiced, but improvement is needed, especially in private settings (10, 47.6%). Significant barriers identified included the high cost of medications (11, 52.4%), insurance-related issues (10, 47.6%), and socioeconomic factors (9, 42.9%). Physician-related barriers, such as time constraints (8, 38.1%) and lack of specialist nursing support (4, 19.0%), were also prominent. System-related barriers included insurance provider policies (13, 61.9%) and gaps in clinical guideline coverage (11, 52.4%). Gender differences in perceived barriers were significant (p=0.016), while age was not (p=0.147)., Conclusions: This study highlights critical barriers to Multiple Sclerosis care in Abu Dhabi, emphasizing the need for policy changes, improved insurance coverage, and targeted support for patients and healthcare providers. Addressing these barriers is essential for enhancing the region's quality of Multiple Sclerosis care and patient outcomes., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Mir et al.)

Metabolic syndrome is a metabolic disorder characterized by hypertension, dyslipidemia, impaired glucose tolerance, and abdominal obesity. Impaired insulin action or insulin resistance initiates metabolic syndrome. The prevalence of insulin resistance is increasing all over the world. Insulin resistance results in the defective metabolism of carbohydrates and lipids, in addition to low-grade chronic inflammation. Insulin resistance is associated with metabolic syndrome, which is a risk factor for a number of pathological conditions, such as Type 2 diabetes (T2D), cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), and polycystic ovarian syndrome (PCOS). Genome-wide association studies have increased our understanding of many loci linked to these diseases and others. In this review, we discuss insulin resistance and its contribution to metabolic syndrome and these diseases. We also discuss the genetic loci associated with them. Genetic testing is invaluable in the identification and stratification of susceptible populations and/or individuals. After susceptible individuals and/or populations have been identified via genetic testing or screening, lifestyle modifications such as regular exercise, weight loss, a healthy diet, and smoking cessation can reduce or prevent metabolic syndrome and its associated pathologies.

Lanthanum (La), a rare earth element (REE) found its wide applications in the agricultural land practices. Utilization of La as a fertilizer is based on its concentration for staple crops, including wheat (Triticum aestivum). We have investigated the role of a beneficial dose of La (60 μM) along with ABA (10 μM) in improving wheat root dynamics and defense systems (ascorbate-glutathione pathway, secondary metabolites, and nitric oxide (NO) biosynthesis). Co-application of La60 and ABA significantly enhanced all the root dynamic attributes along with defense systems and reduced production of reative oxygen species (ROS). The use of the NO inhibitor c-PTIO [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide], proved that the impact of co-application of La60 and ABA on root growth dynamics was mediated by NO biosynthesis. Thus, this study could work as the base to understand the dose-dependent behavior of La in plants, offering valuable implications for enhancing crop resilience, optimizing agricultural practices, and mitigating the detrimental effects of La toxicity on wheat root development. This research gives a comprehensive insight into root dynamics influenced by ABA with La dose optimisations in wheat., (© 2025 Scandinavian Plant Physiology Society.)

Background: Despite the routine clinical use of extracorporeal photopheresis (ECP) for the last decades, there has been no sufficient investigation on the intra-apheresis dynamics of mononuclear cells (MNCs)., Objective: This research aims to verify the "intra-apheresis recruitment" (IAR) of MNCs, which may be particularly useful in cases with low preapheresis MNC counts., Methods: Prospective data of ECP procedures for patients with multiple sclerosis (MS) in the context of the PHOMS study (NCT05168384) were analyzed. ECPs were performed with the use of the Therakos® CellEx® Photopheresis System, and the recruitment factor (RF), collection efficiency 1 (CE 1 ), and fold enrichment (FE) for MNCs, lymphocytes, monocytes, and neutrophils were calculated at various intervals per the approved protocol., Results: A total of 252 ECP procedures were performed on nine patients with MS, and data from 45 ECPs were analyzed for this study. IAR (RF ≥ 1) of MNCs, lymphocytes, and monocytes was observed in the 93.3 %, 95.5 %, and 88.8 % of the ECP procedures, respectively. CE 1 exceeded 100 % for these populations in 13.3 %, 11.1 %, and 24.4 % of ECPs, while FE ≥ 1 for MNCs and lymphocytes was found in all ECPs, and in 97.8 % of ECPs for monocytes. Additionally, RF correlated positively with CE 1 for MNCs (r = 0.40, p = 0.006) and lymphocytes (r = 0.43, p = 0.003), as well as with FE for monocytes (r = 0.39, p = 0.01) and lymphocytes (r = 0.48, p = 0.001), further improving collection quality., Conclusions: Administering photopheresis with suboptimal MNC counts was plausible and did not worsen the anticipated cytopenias. Moreover, our findings revealed sustained IAR of MNCs in patients with MS who underwent ECP., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/objectives: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder associated with gut dysbiosis. To investigate the association between gut microbiota and T2DM in a Saudi Arabian population., Methods: We conducted a comparative analysis of fecal microbiota from 35 individuals, including both T2DM patients and healthy controls. 16S rRNA gene sequencing was employed to characterize the microbial community structure., Results: Our findings revealed significant differences in microbial composition between the two groups. The T2DM group exhibited a higher abundance of Firmicutes and lower levels of Bacteroidetes compared to the healthy control group. At the genus level, T2DM patients showed a decrease in butyrate-producing bacteria such as Bacteroides and Akkermansia, while an increase in Ruminococcus and Prevotella was observed. Additionally, the T2DM group had a higher abundance of Faecalibacterium, Agathobacter, and Lachnospiraceae, along with a lower abundance of Bacteroides., Conclusions: These results suggest that alterations in gut microbiota composition may contribute to the development of T2DM in the Saudi Arabian population. Further large-scale studies are needed to validate these findings and explore potential therapeutic interventions targeting the gut microbiome.

Background: Soil microbes play a vital role in the ecosystem as they are able to carry out a number of vital tasks. Additionally, metagenomic studies offer valuable insights into the composition and functional potential of soil microbial communities. Furthermore, analyzing the obtained data can improve agricultural restoration practices and aid in developing more effective environmental management strategies., Methodology: In November 2023, sandy soil samples were collected from ten sites of different geographical areas surrounding natural lakes and artificial water points in the Tubaiq conservation area of King Salman Bin Abdulaziz Royal Natural Reserve (KSRNR), Saudi Arabia. In addition, genomic DNA was extracted from the collected soil samples, and 16S rRNA sequencing was conducted using high-throughput Illumina technology. Several computational analysis tools were used for gene prediction and taxonomic classification of the microbial groups., Results: In this study, sandy soil samples from the surroundings of natural and artificial water resources of two distinct natures were used. Based on 16S rRNA sequencing, a total of 24,563 OTUs were detected. The metagenomic information was then categorized into 446 orders, 1036 families, 4102 genera, 213 classes, and 181 phyla. Moreover, the phylum Pseudomonadota was the most dominant microbial community across all samples, representing an average relative abundance of 34%. In addition, Actinomycetes was the most abundant class (26%). The analysis of clustered proteins assigned to COG categories provides a detailed understanding of the functional capabilities and adaptation of microbial communities in soil samples. Amino acid metabolism and transport were the most abundant categories in the soil environment., Conclusions: Metagenome analysis of sandy soils surrounding natural lakes and artificial water points in the Tubaiq conservation area of KSRNR (Saudi Arabia) has unveils rich microbial activity, highlighting the complex interactions and ecological roles of microbial communities in these environments.

Background: The human digestive system contains approximately 100 trillion bacteria. The gut microbiota is an emerging field of research that is associated with specific biological processes in many diseases, including cardiovascular disease, obesity, diabetes, brain disease, rheumatoid arthritis, and cancer. Emerging evidence indicates that the gut microbiota affects the response to anticancer therapies by modulating the host immune system. Recent studies have explained a high correlation between the gut microbiota and breast cancer: dysbiosis in breast cancer may regulate the systemic inflammatory response, hormone metabolism, immune response, and the tumor microenvironment. Some of the gut bacteria are related to estrogen metabolism, which may increase or decrease the risk of breast cancer by changing the number of hormones. Further, the gut microbiota has been seen to modulate the immune system in respect of its ability to protect against and treat cancers, with a specific focus on hormone receptor-positive breast cancer. Probiotics and other therapies claiming to control the gut microbiome by bacterial means might be useful in the prevention, or even in the treatment, of breast cancer. Conclusions: The present review underlines the various aspects of gut microbiota in breast cancer risk and its clinical application, warranting research on individualized microbiome-modulated therapeutic approaches to breast cancer treatment.

Heveins are one of the most important groups of plant antimicrobial peptides. So far, various roles in plant growth and development and in response to biotic and abiotic stresses have reported for heveins. The present study aimed to identify and characterize the hevein genes in two-row and six-row cultivars of barley. In total, thirteen hevein genes were identified in the genome of two-row and six-row cultivars of barley. The identified heveins were identical in two-row and six-row cultivars of barley and showed a high similarity with heveins from other plant species. The hevein coding sequences produced open reading frames (ORFs) ranged from 342 to 1002 bp. Most of the identified hevein genes were intronless, and the others had only one intron. The hevein ORFs produced proteins ranged from 113 to 333 amino acids. Search for conserved functional domains showed CBD and LYZ domains in barley heveins. All barley heveins comprised extracellular signal peptides ranged from 19 to 35 amino acids. The phylogenetic analysis divided barley heveins into two groups. The promoter analysis showed regulatory elements with different frequencies between two-row and six-row cultivars. These cis-acting elements included elements related to growth and development, hormone response, and environmental stresses. The expression analysis showed high expression level of heveins in root and reproductive organs of both two-row and six-row cultivars. The expression analysis also showed that barley heveins is induced by both biotic and abiotic stresses. The results of antimicrobial activity prediction showed the highest antimicrobial activity in CBD domain of barley heveins. The findings of the current study can improve our knowledge about the role of hevein genes in plant and can be used for future studies., Competing Interests: Declarations. Competing Interests: The authors have declared that no competing interests exist. Ethical Approval: Not applicable. Consent to Participate: No human subjects or other vulnerable groups have been used for the study. Consent for Publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Blunt thoracic aortic injury (BTAI) represents one of the most devastating scenarios of vascular trauma. Different management strategies are available with varying clinical outcomes. However, thoracic endovascular aortic repair (TEVAR) has become the first-line option for most BTAI patients, mainly owing to its minimally invasive nature, yielding improved immediate results. This meta-analysis aims to investigate mortality, long-term survival, and reintervention following TEVAR in BTAI., Material and Methods: A systematic review conducted a comprehensive literature search on multiple electronic databases using strict search terms. Twenty-seven studies met the set inclusion/exclusion criteria. A proportional meta-analysis of extracted data was conducted using the Comprehensive Meta-Analysis Software, v.4., Results: 1498 BTAI patients who underwent TEVAR were included. Using the SVS grading system, 2.6% of the population had Grade 1 injuries, 13.6% Grade 2, 62.2% Grade 3, 19.6% Grade 4, and 1.9% unspecific. All-cause mortality did not exceed 20% in all studies except one outlier with a 37% mortality rate. Using the random effects model, the pooled estimate of overall mortality was 12% (95% confidence interval [CI], 5.35-8.55%; I 2  = 70.6%). This was 91% (95% CI, 88.6-93.2; I 2  = 30.2%) at 6 months, 90.1% (95% CI, 86.7-92.3; I 2  = 53.6%) at 1 year, 89.2% (95% CI, 85.2-91.8; I2 = 62.3%) at 2 years, and 88.1% (95% CI, 83.3-90.9; I 2  = 69.6%) at 5 years. Moreover, the pooled estimate of reintervention was 6.4% (95% CI, 0.1-0.49%; I 2  = 81.7%)., Conclusions: Despite the high morbidity and mortality associated with BTAI, TEVAR has proven to be a safe and effective management strategy with favorable long-term survival and minimal need for reintervention. Nevertheless, diagnosis of BTAI requires a high index of suspicion with appropriate grading and prompt transfer to trauma centers with appropriate TEVAR facilities., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Obesity, a global health concern, is associated with severe health issues like type 2 diabetes, heart disease, and respiratory complications. It also increases the risk of various cancers, including melanoma, endometrial, prostate, pancreatic, esophageal adenocarcinoma, colorectal carcinoma, renal adenocarcinoma, and pre-and post-menopausal breast cancer. Obesity-induced cellular changes, such as impaired CD8 + T cell function, dyslipidemia, hypercholesterolemia, insulin resistance, mild hyperglycemia, and fluctuating levels of leptin, resistin, adiponectin, and IL-6, contribute to cancer development by promoting inflammation and creating a tumor-promoting microenvironment rich in adipocytes. Adipocytes release leptin, a pro-inflammatory substance that stimulates cancer cell proliferation, inflammation, and invasion, altering the tumor cell metabolic pathway. Adiponectin, an insulin-sensitizing adipokine, is typically downregulated in obese individuals. It has antiproliferative, proapoptotic, and antiangiogenic properties, making it a potential cancer treatment. This narrative review offers a comprehensive examination of the molecular interconnections between obesity and cancer, drawing on an extensive, though non-systematic, survey of the recent literature. This approach allows us to integrate and synthesize findings from various studies, offering a cohesive perspective on emerging themes and potential therapeutic targets. The review explores the metabolic disturbances, cellular alterations, inflammatory responses, and shifts in the tumor microenvironment that contribute to the obesity-cancer link. Finally, it discusses potential therapeutic strategies aimed at disrupting these connections, offering valuable insights into future research directions and the development of targeted interventions., Competing Interests: 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., (© 2024 Chinese National Cancer Center. Published by Elsevier B.V.)

Covid-19 caused by SARS-CoV-2 virus has emerged as an immense burden and an unparalleled global health challenge in recorded human history. The clinical characteristics and risk factors of COVID-19 exhibit considerable variability, leading to a spectrum of clinical severity. Moreover, the likelihood of exposure to the virus may differ based on comorbidity status as comorbid illnesses have mechanisms that can considerably increase mortality by reducing the body's ability to withstand injury. The mammalian target of rapamycin (mTOR) pathway is essential for orchestrating innate immune cell defense, including cytokine production and is dysregulated in severe Coronavirus Disease 2019 (COVID-19) individuals. Through genome-wide, association studies, numerous genetic variants in the human host have been identified that have a significant impact on the immune response to SARS-CoV-2. To identify potentially significant genetic variants in Covid-19 patients that could affect the risk, severity, and clinical outcome of the infection, this study has used whole-exome sequencing (WES) on the 16 COVID-19 patients with varying comorbidities and severity of the disease including fatal outcomes. Among them, 8 patients made a full recovery and were discharged, while 8 patients unfortunately did not survive due to the severity of the illness and majority of them were males. The study identified 10,204 variants in the patients. From 1120 variants, which were chosen for novel variant analysis using mutation, function prediction tools to identify deleterious variants that could affect normal gene function, 116 variants of 57 genes were found to be deleterious. These variants were further classified as likely pathogenic and variants of uncertain significance. The data showed that among the likely pathogenic variants five genes were identified in connection to immune response whereas two were related to respiratory system. The common variants associated with the covid-19 phenotype showed the top 10 significant genes identified in this study such as ERCC2, FBXO5, HTR3D, FAIM, DNAH17, MTOR, IGHMBP2, ZNF530, QSER1, and FOXRED2 with variant rs1057079 of the MTOR gene representing the highest odds ratio (1.7, p = 8.7e-04). The mammalian target of rapamycin (mTOR) pathway variant rs1057079 was reported with high odds ratio, may orchestrate innate immune cell defense, including cytokine production, and is dysregulated. This study concluded that the mTOR signaling gene variant (rs1057079) is associated with different degrees of covid-19 severity and is essential for orchestrating innate immune cell defense including cytokine production. Inhibiting mTOR and its corresponding deleterious immune responses with medicinal approaches may provide a novel avenue for treating severe COVID-19 illness. Besides the PPI network exhibited a significantly high local clustering coefficient of 0.424 (p = 0.000536), suggesting the presence of tightly knit functional modules. These findings enhance our comprehension of the intricate interactions between genetic factors and COVID-19 disease., Competing Interests: Declarations. Competing Interest: The authors declare no competing interests. Ethical Approval: The study was approved by the institutional ethics committees at the University of Bisha (Ref. no. UBCOM/H-06-BH-087(05/25)). All the subjects provided written informed consent before their participation in the study., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

La centralización de los partos de alto riesgo en los hospitales con el más alto nivel de atención es fundamental para ampliar el margen de seguridad materno-neonatal y mejorar los desenlaces. Por lo tanto, es altamente recomendable trasladar oportunamente a las pacientes gestantes portadoras de embarazos de alto riesgo y/o con amenazas de parto pretérmino a centros de atención terciaria, sin embargo, no siempre es posible anticipar los riesgos antenatalmente, lo cual resulta en la necesidad de trasladar a neonatos en estado crítico. Lamentablemente, la movilización de los recién nacidos compromete aún más su estado de salud, especialmente en los países latinoamericanos. El presente trabajo resume los resultados del XIII Consenso Clínico de SIBEN de Traslado Neonatal, en el cual colaboraron 65 miembros de SIBEN, neonatólogos y licensiados en enfermería de 14 países de Iberoamérica, que participaron activamente durante el 2022, antes, durante y después de la reunión presencial que se llevó a cabo en Mérida, Yucatán, México el 12 de noviembre del 2022. En esta reunión se consensuaron las recomendaciones aquí vertidas., (Copyright © 2024 by the American Academy of Pediatrics.)

The Tabuk region is located in the northern part of Saudi Arabia, and it has an area of 117,000 km 2 between longitudes 26° N and 29° N and latitudes 34° E and 38° E. King Salman Bin Abdulaziz Royal Natural Reserve (KSRNR) is the largest natural reserve in Saudi Arabia and covers about 130,700 km 2 . It represents a new tourist attraction area in the Tabuk region. Human activities around the lake may lead to changes in water quality, with subsequent changes in microenvironment components, including microbial diversity. The current study was designed to assess possible changes in bacterial communities of the water sediment at some natural lakes and artificial waterpoints of KSRNR. Water samples were collected from ten different locations within KSRNR: W1, W2, W3 (at the border of the royal reserve); W4, W5, W6, W7 (at the middle); and W8, W9, and W10 (artificial waterpoints). The total DNA of the samples was extracted and subjected to 16S rRNA sequencing and metagenomic analysis; also, the environmental parameters (temperature and humidity) were recorded for all locations. Metagenomic sequencing yielded a total of 24,696 operational taxonomic units (OTUs), which were subsequently annotated to 193 phyla, 215 classes, 445 orders, 947 families, and 3960 genera. At the phylum level, Pseudomonadota dominated the microbial communities across all samples. At the class level, Gammaproteobacteria , Clostridia , Alphaproteobacteria , Bacilli , and Betaproteobacteria were the most prevalent. The dominant families included Enterobacteriaceae , Pseudomonadaceae , Clostridiaceae , Comamonadaceae , and Moraxellaceae . At the genus level, Pseudomonas , Clostridium , Acinetobacter , Paenibacillus , and Acidovorax exhibited the highest relative abundances. The most abundant species were Hungatella xylanolytica , Pseudescherichia vulneris , Pseudorhizobium tarimense , Paenibacillus sp. Yn15 , and Enterobacter sp. Sa187 . The observed species richness revealed substantial heterogeneity across samples using species richness estimators, Chao1 and ACE, indicating particularly high diversity in samples W3, W5, and W6. Current study results help in recognizing the structure of bacterial communities at the Tubaiq area in relation to their surroundings for planning for environmental protection and future restoration of affected ecosystems. The findings highlight the dominance of various bacterial phyla, classes, families, and genera, with remarkable species richness in some areas. These results underscore the influence of human activities on microbial diversity, as well as the significance of monitoring and conserving the reserve's natural ecosystems.

Background: Insufficient vitamin D (vit D) levels are associated with various chronic conditions such as cancers, autoimmune diseases, diabetes, and cardiovascular diseases, notably coronary artery disease (CAD). The enzyme 25-hydroxylase, cytochrome P450 2R1 (CYP2R1), catalyzes the hydroxylation of vitamin D in the liver, producing the 25-hydroxyvitamin D, which is then activated in the kidney by cytochrome P450 27B1 (CYP27B1) to form 1,25-dihydroxyvitamin D. Mutations in the CYP2R1 gene can impair vitamin D production. The C-C chemokine receptor type 5 (CCR5) supports endothelial repair and angiogenesis, with its mutation ( CCR5 59029 G to A) being linked to insulin resistance and type 2 diabetes (T2D). Additionally, the transcription factor 7-like 2 (TCF7L2), part of the Wnt signaling pathway, regulates glucose homeostasis and the development of tissues, brain, liver and muscles and has been linked to obesity, insulin insensitivity, and elevated blood sugar levels., Materials and Methods: We evaluated the association of reduced serum vitamin D levels with CAD using enzyme-linked immunosorbent assay (ELISA). Genotyping of the CYP2R1 rs1562902 C > T, TCF7L2 rs12255372 G > T, and CCR5 Δ32 bp deletion mutation were performed using amplification-refractory mutation system polymerase chain reaction (PCR) and allele-specific PCR to evaluate their association with CAD risk., Results: The CYP2R1 rs1562902 C > T single nucleotide polymorphism (SNP) genotypes CT and TT were significantly associated with CAD, with odds ratios (ORs) of 4.1 and 7.6 and p -values of 0.0001 and 0.0008, respectively. The +/Δ genotype of the CCR5 Δ32 bp (ins/del) mutation was also associated with CAD (OR = 2.51, p = 0.006). Additionally, the T allele of the TCF7L2 rs12255372 G > T SNP was linked to an increased risk of CAD (OR = 1.89, p = 0.006)., Conclusion: The CYP2R1 rs1562902 C > T, CCR5 Δ32 (rs333), and TCF7L2 rs12255372 G > T polymorphisms are potential genetic loci associated with increased CAD risk. Furthermore, CYP2R1 variants are associated with vitamin D deficiency, predisposing carriers of CYP2R1 to associated pathologies. These findings warrant further validation through larger case-control studies and functional protein analysis.

Salinity is an increasing problem for agriculture. Most plant species tolerate low or, at best, moderate soil salinities. However, a small (<1%) proportion of species, termed halophytes, can survive and complete their life cycle in natural habitats with salinities equivalent to 200 mM NaCl or more. Cakile maritima is a succulent annual halophyte belonging to the Brassicaceae family; it is dispersed worldwide and mainly grows in foreshores. Cakile maritima growth is optimal under slight (i.e., 100 mM NaCl) saline conditions, measured by biomass and seed production. Higher salt concentrations, up to 500 mM NaCl, significantly impact its growth but do not compromise its survival. Cakile maritima alleviates sodium toxicity through different strategies, including anatomical and morphological adaptations, ion transport regulation, biosynthesis of osmolytes, and activation of antioxidative mechanisms. The species is potentially useful as a cash crop for the so-called biosaline agriculture due to its production of secondary metabolites of medical and nutritional interest and the high oil accumulation in its seeds. In this review, we highlight the relevance of this species as a model for studying the basic mechanisms of salt tolerance and for sustainable biosaline agriculture in the context of soil salination and climate change.

Extracellular vehicles (EVs) are gaining increasing recognition as central contributors to the intricate landscape of the tumor microenvironment (TME). This manuscript provides an extensive examination of the multifaceted roles played by EVs in shaping the TME, with a particular emphasis on their involvement in metastasis, drug resistance, and immune evasion. Metastasis, the process by which cancer cells disseminate to distant sites, remains a formidable challenge in cancer management. EVs, encompassing exosomes and microvesicles, have emerged as critical participants in this cascade of events. They facilitate the epithelial-to-mesenchymal transition (EMT), foster pre-metastatic niche establishment, and enhance the invasive potential of cancer cells. This manuscript delves into the intricate molecular mechanisms underpinning these processes, underscoring the therapeutic potential of targeting EVs to impede metastasis. Drug resistance represents a persistent impediment to successful cancer treatment. EVs are instrumental in intrinsic and acquired drug resistance, acting as mediators of intercellular communication. They ferry molecules like miRNAs and proteins, which confer resistance to conventional chemotherapy and targeted therapies. This manuscript scrutinizes the diverse strategies employed by EVs in propagating drug resistance while also considering innovative approaches involving EV-based drug delivery systems to counteract this phenomenon. Immune evasion is a hallmark of cancer, and EVs are central in sculpting the immunosuppressive milieu of the TME. Tumor-derived EVs thwart immune responses through various mechanisms, including T cell dysfunction induction, the expansion of regulatory T cells (Tregs), and polarization of macrophages towards an immunosuppressive phenotype. In addition, the manuscript explores the diagnostic potential of EVs as biomarkers and their role as therapeutic agents in immune checkpoint blockade therapies. This manuscript provides a comprehensive overview of EV's pivotal role in mediating intricate interactions within the TME, ultimately influencing cancer progression and therapeutic outcomes. A profound understanding of EV-mediated processes in metastasis, drug resistance, and immune evasion opens up promising avenues for developing innovative therapeutic strategies and identifying valuable biomarkers in the ongoing battle against cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

This paper examines the integration of artificial intelligence (AI) in radiotherapy for cancer treatment. The importance of radiotherapy in cancer management and its time-intensive planning process make AI adoption appealing especially with the escalating demand for radiotherapy. This review highlights the efficacy of AI across medical domains, where it surpasses human capabilities in areas such as cardiology and dermatology. Focusing on radiotherapy, the paper details AI's applications in target segmentation, dose optimization, and outcome prediction. It discusses adaptive radiotherapy's benefits and AI's potential to enhance patient outcomes with much improved treatment accuracy. The paper explores ethical concerns, including data privacy and bias, stressing the need for robust guidelines. Educating healthcare professionals and patients about AI's role is crucial as it acknowledges potential job-role changes and concerns about patients' trust in the use of AI. Overall, the integration of AI in radiotherapy holds transformative potential in streamlining processes, improving outcomes, and reducing costs. AI's potential to reduce healthcare costs underscores its significance with impactful change globally. However, successful implementation hinges on addressing ethical and logistical challenges and fostering collaboration among healthcare professionals and patient population data sets for its optimal utilization. Rigorous education, collaborative efforts, and global data sharing will be the compass guiding its' success in radiotherapy and healthcare., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) illness led to the coronavirus disease 2019 (COVID-19) pandemic, which has caused enormous health and financial losses, as well as challenges to global health. Iron deficiency anaemia (IDA) has been linked to adverse outcomes in patients infected with SARS-COV-2. The present study aimed to assess the association between IDA and the severity of COVID-19 in hospitalized patients. For this purpose, a retrospective data analysis of 100 patients with COVID-19 was conducted. Data of patients hospitalized with SARS-COV-2 infection confirmed by RT-PCR were collected between June, 2021 and March, 2022. The collected data included patient demographics, comorbidities, clinical signs, symptoms and IDA medical laboratory findings, including complete blood count and iron profiles. The results revealed that patients with COVID-19 admitted to the isolation unit represented 61.0% of the study sample, whereas 39.0% were admitted to the intensive care unit (ICU). No patients had stage I IDA, whereas 4 patients (4%) had stage II IDA. Furthermore, 19 patients (19.0%) had stage III IDA. A significantly higher proportion of patients with IDA (69.6%) were admitted to the ICU compared with those without IDA (29.9%, P<0.001). Additionally, patients with IDA had a higher proportion of a history of stroke compared with those without IDA (17.4 vs. 2.6%, respectively, P=0.024). The most common comorbidities identified were hypertension (29%), diabetes (23%) and heart problems (17%). On the whole, the present study demonstrates significant associations between IDA and a longer hospitalization period. A greater incidence of complications was observed in the hospitalized patients who were SARS-COV-2-positive. Although further studies with larger sample sizes are required to confirm these findings, the results presented herein may provide insight for physicians as regards the prevention and treatment of patients with IDA who are infected with coronavirus., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Jalal et al.)

Introduction: Esophageal squamous cell carcinoma (ESCC) accounts for over 90% of all esophageal tumors. However, the molecular mechanism underlying ESCC development and prognosis remains unclear, and there are still no effective molecular biomarkers for diagnosing or predicting the clinical outcome of patients with ESCC. Here, we used bioinformatics analysis to identify potential biomarkers and therapeutic targets for ESCC. Methodology: Differentially expressed genes (DEGs) between ESCC and normal esophageal tissue samples were obtained by comprehensively analyzing publicly available RNA-seq datasets from the TCGA and GTEX. Gene Ontology (GO) annotation and Reactome pathway analysis identified the biological roles of the DEGs. Moreover, the Cytoscape 3.10.1 platform and subsidiary tools such as CytoHubba were used to visualize the DEGs' protein-protein interaction (PPI) network and identify hub genes, Furthermore our results are validated by using Single-cell RNA analysis. Results: Identification of 2524 genes exhibiting altered expression enriched in pathways including keratinization, epidermal cell differentiation, G alpha(s) signaling events, and biological process of cell proliferation and division, extracellular matrix (ECM) disassembly, and muscle function. Moreover, upregulation of hallmarks E2F targets, G2M checkpoints, and TNF signaling. CytoHubba revealed 20 hub genes that had a valuable influence on the progression of ESCC in these patients. Among these, the high expression levels of four genes, CDK1 MAD2L1, PLK1, and TOP2A, were associated with critical dependence for cell survival in ESCC cell lines, as indicated by CRISPR dependency scores, gene expression data, and cell line metadata. We also identify the molecules targeting these essential hub genes, among which GSK461364 is a promising inhibitor of PLK1, BMS265246, and Valrubicin inhibitors of CDK1 and TOP2A, respectively. Moreover, we identified that elevated expression of MMP9 is associated with worse overall survival in ESCC patients, which may serve as potential prognostic biomarker or therapeutic target for ESCC. The single-cell RNA analysis showed MMP9 is highly expressed in myeloid, fibroblast, and epithelial cells, but low in T cells, endothelial cells, and B cells. This suggests MMP9's role in tumor progression and matrix remodeling, highlighting its potential as a prognostic marker and therapeutic target. Discussion: Our study identified key hub genes in ESCC, assessing their potential as therapeutic targets and biomarkers through detailed expression and dependency analyses. Notably, MMP9 emerged as a significant prognostic marker with high expression correlating with poor survival, underscoring its potential for targeted therapy. These findings enhance our understanding of ESCC pathogenesis and highlight promising avenues for treatment., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Khurshid, Usmani, Ali, Hamid, Masoodi, Sadida, Ahmed, Khan, Abeer, Albalawi, Bedaiwi, Mir, Al-Shabeeb Akil, Bhat and Macha.)

Purpose: The study aimed to correlate macular ganglion cell layer + inner plexiform layer (GCL + IPL) thickness and circumpapillary retinal nerve fiber layer (cRNFL) thickness and to determine the validity of GCL + IPL in the evaluation of glaucoma across different stages using the area under the curve (AUC) analysis in comparison to cRNFL., Patients and Methods: The charts of 260 adult glaucoma suspect and glaucoma patients having macular ganglion cell analysis, optical coherence tomography (OCT) of the cRNFL and automated visual field (AVF) were reviewed. GCL + IPL thickness (average, minimum and sectoral) and sectoral cRNFL thickness were obtained. Glaucomatous eyes were further classified into stages based on the Hodapp-Anderson-Parrish Visual Field Criteria of Glaucoma Severity. AUC analysis was used to compare GCL + IPL parameters with cRNFL in glaucoma suspects and glaucoma patients., Results: A total of 122 eyes were included in the study and were grouped into glaucoma suspects (n = 43), early or mild glaucoma (n = 40), and moderate-to-severe glaucoma (n = 39). Both GCL + IPL and cRNFL thickness parameters showed a significant decline with greater glaucoma severity. In the determination of visual field defects across all glaucoma stages, the highest AUC was obtained by minimum GCL + IPL (AUC = 0.859) with cut-off value at ≤70 µm. Average GCL + IPL had the highest AUC (0.835) in detecting progression from glaucoma suspect to mild glaucoma, while the inferior sector of the cRNFL had the highest AUC (0.937) in discerning mild from moderate-to-severe glaucoma., Conclusion: The results of this study highlight the significance of macular ganglion cell analysis in the screening, detection and staging of glaucoma. Compared to cRNFL, macular ganglion analysis may be more beneficial in glaucoma screening and detecting progression from glaucoma suspect to mild glaucoma., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 San Pedro et al.)

Rare earth elements (REEs) comprises of a uniform group of lanthanides and scandium (Sc) and yttrium (Y) finding their key importance in agriculture sectors, electronic and defense industries, and renewable energy production. The immense application of REEs as plant growth promoters has led to their undesirable accumulation in the soil system raising concerns for REE pollution as upcoming stresses. This review mainly addresses the chemistry of REEs, uptake and distribution and their biphasic responses in plant systems and possible plausible techniques that could mitigate/alleviate REE contamination. It extends beyond the present understanding of the biphasic impacts of rare earth elements (REEs) on physio-biochemical attributes. It not only provides landmarks for further exploration of the interrelated phytohormonal and molecular biphasic nature but also introduces novel approaches aimed at mitigating their toxicities. By delving into innovative strategies such as recycling, substitution, and phytohormone-assisted mitigation, the review expands upon existing knowledge of REEs whilst also offering pathways to tackle the challenges associated with REE utilization., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The newly constituted National Multiple Sclerosis (MS) Society (NMSS)of the United Arab Emirates (UAE), set up a scientific committee to create a MS disease modifying treatment (DMT) guideline for UAE. The committee considered several unique features of the MS community in UAE including large number of expatriate population, wide variations in health insurance coverage, physician and patient preferences for DMT. The overall goal of the treatment guideline is to facilitate the most appropriate DMT to the widest number of patients. To this end it has adapted recommendations from various health systems and regulatory authorities into a pragmatic amalgamation of best practices from across the world. Importantly where data is unavailable or controversial, a common sense approach is taken rather than leave physicians and patients in limbo. The committee classifies MS into subcategories and suggests appropriate treatment choices. It recommends treatment of RIS and CIS with poor prognostic factors. It largely equates the efficacy and safety of DMT with similar mechanisms of action or drug classes e.g. ocrelizumab is similar to rituximab. It allows early switching of treatment for unambiguous disease activity and those with progression independent of relapses. Autologous hematopoietic stem cell transplantation can be offered to patients who fail one high efficacy DMT. Pragmatic guidance on switching and stopping DMT, DMT choices in pregnancy, lactation and pediatric MS have been included. It is expected that these guidelines will be updated periodically as new data becomes available., Competing Interests: Declaration of competing interest Anu Jacob has received advisory board fees and speakers fee from Astra Zeneca. Ahmed Shatila has received speaker's honoraria, advisory board fees, travel grants from Novartis, Sanofi Genzyme, Roche, Merck, Jansen, Biologix, pfizer, Boehringer Ingelheim, AstraZeneca, Lundbeck and Argenx, Bayer, Biogen and received research grants from Novartis, AstraZeneca and Argenx. Jihad Inshasi has received speaker's honoraria from Bayer, Biogen, Biologix, Merck, Novartis, Roche, Sanofi; Research grants from Merck, Novartis; Advisory board fees from Bayer, Biogen,Merck, Novartis, Roche, Sanofi Joelle Massouh has received speakers’ honoraria, travel, grants and advisory board fees from AstraZeneca, Biogen, Biologix, Janssen, Merck, Novartis, Roche, and Sanofi. Ruquia Mir has received speaker's honoraria, advisory board fees and travel grants from Merck Sanofi Novartis Roche Suzan Noori has no disclosures. Bassem Yamout has received speaker's honoraria travel, grants and advisory board fees from Bayer, Biogen, Biologix, Genpharm, Merck, Novartis, Roche, Sanofi, Genzyme and research grants from Bayer, Biogen, Biologix, Merck, Novartis, Pfizer, (Copyright © 2024. Published by Elsevier B.V.)

PCOS is a heterogeneous, multifactorial endocrine disorder with a complex pathophysiology. It is a globally rising infertility disorder that affects a large percentage of women of reproductive age, with a relatively high prevalence of 8-13%. Genome-wide association studies have revealed associations of genetic variations with many diseases, including PCOS. The cellular activity of IL8 is mediated by the receptor CXCR2, and transcription of IL8 is controlled by TNF-α. Therefore, this study aimed to investigate the association of TNF-α, CCR5-delta32, and CXCR2 gene variations with PCOS., Methodology: In this case control study, we used amplification-refractory mutation system (ARMS)-PCR to detect and determine the presence of the polymorphic variants TNF-α, CCR5-delta32, and CXCR2 in the study subjects. These gene polymorphs may serve as critical candidate gene variants in PCOS pathogenesis and therapeutics., Results: The case-control study's findings revealed that the majority of the biochemical and endocrine serum biomarkers examined in the investigation-including lipids (LDL, HDL, and cholesterol), T2DM markers (fasting glucose, free insulin, and HOMA-IR), and hormones (FSH, LH, testosterone, and progesterone)-exhibited statistically significant changes in PCOS patients. The distributions of TNF-α (rs1800629), CCR5-delta32, and CXCR2 (rs2230054) genotypes analyzed within PCOS patients and healthy controls in the considered population were significant ( p < 0.05). The heterozygosity of CXCR2-CA, TNF-α GA, and CCR5(WT+Δ32*) genotypes was significantly associated with PCOS susceptibility, with high OR and p < 0.05 in the codominant model. Similarly, the A allele of the TNF-α and CXCR2 genes, along with the CCR5Δ32*(mutant) allele, was significantly associated with PCOS susceptibility, with high OR and p < 0.05. Likewise, the CXCR2 (CA+AA) vs CC genotype was associated with increased susceptibility to PCOS, with OR 2.25, p < 0.032., Conclusions: Our study concludes that TNF-α rs1800629G>A, CXCR2-rs2230054C>T, and CCR5-Delta32 rs333 are potential loci for developing PCOS in the Tabuk population. These findings might eventually be useful in identifying and classifying those who are at risk for PCOS. To validate these results, it is advised that further longitudinal studies be conducted in diverse ethnic populations and with larger sample sizes.

Background: Health policy promotes patient participation in decision making about service organisation. In English general practice this happens through contractually required patient participation groups (PPGs). However, there are problems with the enactment of PPGs that have not been systematically addressed., Aim: To observe how a co-designed theory-informed intervention can increase representational legitimacy and facilitate power sharing to support PPGs to influence decision making about general practice service improvement., Design and Setting: Participatory action research to implement the intervention in two general practices in the North of England was undertaken. The intervention combined two different participatory practices: partnership working involving externally facilitated meetings with PPG members and staff; and consultation with the wider patient population using a bespoke discrete choice experiment (DCE)., Method: To illustrate decision making in PPGs, qualitative data are presented from participant observation notes and photographed visual data generated through participatory methods. The DCE results are summarised to illustrate how wider population priorities contributed to overall decision making. Observational data were thematically analysed using normalisation process theory with support from a multi-stakeholder co-research group., Results: In both general practices, patients influenced decision making during PPG meetings and through the DCE, resulting in bespoke patient-centred action plans for service improvement. Power asymmetries were addressed through participatory methods, clarification of PPG roles in decision making, and addressing representational legitimacy through wider survey consultation., Conclusion: Combining participatory practices and facilitated participatory methods enabled patients to influence decision making about general practice service improvement. The policy of mandatory PPGs needs updating to recognise the need to resource participation in a meaningful way., (© The Authors.)

Background: Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in developing nations. The high prevalence of obesity and related diabetes cases are attributed to rapid economic progress, physical inactivity, the consumption of high-calorie foods, and changing lifestyles., Objectives: We investigated the roles of pro-inflammatory chemokines CCL1, 2, 4, and 5 in T2DM with varying levels of obesity in the Asir region of Saudi Arabia., Materials and Methods: In total, 170 confirmed T2DM subjects and a normal control group were enrolled. Demographic data, serum levels of CCL-1, 2, 4, and 5, and biochemical indices were assessed in the subjects and control groups by standard procedures., Results: T2DM subjects were divided into four groups: A (normal body weight), B (overweight), C (obese), and D (highly obese). We observed that male and female control subjects had similar mean serum concentrations of pro-inflammatory chemokines CCL-1, 2, 4, and 5. T2DM subjects in all the four groups showed significantly higher levels of all the four chemokines compared to the controls, regardless of gender. In T2DM subjects with obesity and severe obesity, the rise was most significant. There was a progressive rise in the concentrations of CCL-1, 2, and 4 in T2DM subjects with increasing BMI. Serum CCL5 levels increased significantly in all T2DM subject groups. The increase in CCL5 was more predominant in normal-weight people, compared to overweight and obese T2DM subjects., Conclusions: Male and female control subjects had similar serum levels of pro-inflammatory chemokines CCL-1, 2, 4, and 5. The progressive rise in blood concentrations of three pro-inflammatory chemokines CCL-1, 2, and 4 in T2DM subjects with increasing BMI supports the idea that dyslipidemia and obesity contribute to chronic inflammation and insulin resistance. Serum CCL5 levels increased significantly in all T2DM subject groups. The selective and more pronounced increase in CCL5 in the T2DM group with normal BMI, compared to subjects with varying degrees of obesity, was rather surprising. Further research is needed to determine if CCL5 underexpression in overweight and obese T2DM subjects is due to some unexplained counterbalancing processes.

Background: In recent years, various coronaviruses have caused severe respiratory illnesses worldwide. For example the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections of COVID-19 outbreak in 2019 in Wuhan, China. Genome-wide association studies (GWAS) have significantly expanded our comprehension of how specific genetic variations are linked to diseases. Research has demonstrated the existence of genetic factors influencing susceptibility to coronaviruses. The objective of this study was to examine the association of certain loci with the COVID-19 in Saudi population., Methods: In the present study we have examined the link between the COVID-19 disease and certain genetic variants in hospitalized COVID-19 patients (n = 16) in Tabuk and Bisha, Kingdom Saudi Arabia. We used the genome Analysis Toolkit (GATK) and Comprehensive variant annotation was performed different databases and tools such as Search Tool for the Retrieval of Interacting Genes (STRING), PanelApp and PolyPhen-2., Results: The study showed that the genetic variants associated with genes such as Homeostatic Iron Regulator ( HFE ) (found in 7 patients, representing 44%), complement factor H ( CFH ) (6 patients, 38%), cadherin 23 ( CDH23 ) (4 patients, 25%), cytotoxic T-lymphocyte associated protein 4 ( CTLA-4 ) (3 patients, 19%), Transforming Growth Factor Beta 1 ( TGFB1 ) (3 patients, 19%), CREB-binding protein ( CREBBP ) (2 patients, 13%), E1A Binding Protein P300 ( EP300 ) (2 patients, 13%), hemoglobin subunit beta ( HBB ) (2 patients, 13%), interferon regulatory factor 7 ( IRF7 ) (2 patients, 13%), and unc-119 lipid binding chaperone ( UNC119 ) (2 patients, 13%) might be associated with susceptibility to coronavirus. We also identified mutations in the COVID-19 patient that are pathogenic or likely pathogenic., Conclusion: A recurrent pathogenic mutation, HFE p.His63Asp (H63D), was identified in 7 patients, suggesting its potential contribution to disease severity. Additionally, a likely pathogenic variant, HBB p.Glu7Val (E7V), was present in 2 patients, highlighting its potential role in disease susceptibility. Our results shed light on the key genetic mechanisms of COVID-19 pathogenesis and help to identify and stratify the individuals or populations that are at risk to corona virus infection. The identification of susceptible individuals or populations assist in prevention and/or in treatment programs.

Diabetes mellitus (DM) represents a problem for the healthcare system worldwide. DM has very serious complications such as blindness, kidney failure, and cardiovascular disease. In addition to the very bad socioeconomic impacts, it influences patients and their families and communities. The global costs of DM and its complications are huge and expected to rise by the year 2030. DM is caused by genetic and environmental risk factors. Genetic testing will aid in early diagnosis and identification of susceptible individuals or populations using ATP-sensitive potassium (K ATP ) channels present in different tissues such as the pancreas, myocardium, myocytes, and nervous tissues. The channels respond to different concentrations of blood sugar, stimulation by hormones, or ischemic conditions. In pancreatic cells, they regulate the secretion of insulin and glucagon. Mutations in the KCNJ11 gene that encodes the Kir6.2 protein (a major constituent of K ATP channels) were reported to be associated with Type 2 DM, neonatal diabetes mellitus (NDM), and maturity-onset diabetes of the young (MODY). Kir6.2 harbors binding sites for ATP and phosphatidylinositol 4,5-diphosphate (PIP2). The ATP inhibits the K ATP channel, while the (PIP2) activates it. A Kir6.2 mutation at tyrosine330 (Y330) was demonstrated to reduce ATP inhibition and predisposes to NDM. In this study, we examined the effect of mutations on the Kir6.2 structure using bioinformatics tools and molecular dynamic simulations (SIFT, PolyPhen, SNAP2, PANTHER, PhD&SNP, SNP&Go, I-Mutant, MuPro, MutPred, ConSurf, HOPE, and GROMACS). Our results indicated that M199R, R201H, R206H, and Y330H mutations influence Kir6.2 structure and function and therefore may cause DM. We conclude that MD simulations are useful techniques to predict the effects of mutations on protein structure. In addition, the M199R, R201H, R206H, and Y330H variant in the Kir6.2 protein may be associated with DM. These results require further verification in protein-protein interactions, Kir6.2 function, and case-control studies.

Cancer is a complex disease displaying a variety of cell states and phenotypes. This diversity, known as cancer cell plasticity, confers cancer cells the ability to change in response to their environment, leading to increased tumor diversity and drug resistance. This review explores the intricate landscape of cancer cell plasticity, offering a deep dive into the cellular, molecular, and genetic mechanisms that underlie this phenomenon. Cancer cell plasticity is intertwined with processes such as epithelial-mesenchymal transition and the acquisition of stem cell-like features. These processes are pivotal in the development and progression of tumors, contributing to the multifaceted nature of cancer and the challenges associated with its treatment. Despite significant advancements in targeted therapies, cancer cell adaptability and subsequent therapy-induced resistance remain persistent obstacles in achieving consistent, successful cancer treatment outcomes. Our review delves into the array of mechanisms cancer cells exploit to maintain plasticity, including epigenetic modifications, alterations in signaling pathways, and environmental interactions. We discuss strategies to counteract cancer cell plasticity, such as targeting specific cellular pathways and employing combination therapies. These strategies promise to enhance the efficacy of cancer treatments and mitigate therapy resistance. In conclusion, this review offers a holistic, detailed exploration of cancer cell plasticity, aiming to bolster the understanding and approach toward tackling the challenges posed by tumor heterogeneity and drug resistance. As articulated in this review, the delineation of cellular, molecular, and genetic mechanisms underlying tumor heterogeneity and drug resistance seeks to contribute substantially to the progress in cancer therapeutics and the advancement of precision medicine, ultimately enhancing the prospects for effective cancer treatment and patient outcomes., (© 2024. The Author(s).)

Background: Altered cytokine levels have been associated with poor outcomes among COVID-19 patients. TNF-α, IL-8 and IL-10 are key cytokines in COVID-19 pathogenesis, and CXCR-2 is a major chemokine receptor involved in inflammatory response. Polymorphisms in the genes of these proteins are proposed to influence disease outcomes. In this study, we aimed to find out the association of genetic polymorphisms in TNF-α, IL-8, IL-10 and CXCR-2 genes with susceptibility to and mortality of COVID-19., Methods: The present case-control study was conducted on 230 subjects, among whom 115 were clinically diagnosed and RT-PCR-confirmed COVID-19 patients and 115 healthy control subjects. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), CXCR2 +785 C>T (rs2230054) genes were detected by ARMS -PCR assay whereas for IL-10 (-1082 G>A), rs1800896 G>A allele-specific PCR assay was used and their association with COVID-19 susceptibility and mortality was estimated by multivariate analysis. The results were analyzed for risk of infection and mortality through different inheritance models., Results: Frequencies of TNF-α rs1800629 GA, AA, IL-8 rs4073 TA, AA, IL-10 (-1082 G>A), rs1800896 GA and GG, and CXCR2 rs2230054 CT genotypes were significantly higher in COVID-19 patients compared to the control group ( p < 0.05). Furthermore, COVID-19 patients had a higher frequency of the polymorphic A allele of TNF-α, the A allele of IL-8, the G allele of IL-10, and the T allele of CXCR2. The risk of susceptibility to COVID-19 was significantly associated with TNF-α rs1800629 GA, GA+AA genotypes and the A allele, IL-8 rs4073 TA, AA genotypes and A allele, IL-10 rs1800872 GA and CC genotypes and C allele, and CXCR2 rs2230054 CT and CT+CC genotypes. TNF-α-GA and AA genotypes and A allele, IL-8 TA and AA genotypes and A allele and CXCR-2 CC and CT genotypes have significant associations with mortality risk in COVID-19 patients, while GA and GG genotypes of the IL-10 are shown to confer significant protection against mortality from COVID-19., Conclusion: The findings of this study provide important insights into the COVID-19 disease and susceptibility risk. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), IL-10 (-1082 G>A), rs1800896 and CXCR2 +785 C>T (rs2230054) are associated with the risk of susceptibility to COVID-19 and with mortality in COVID-19 patients. Further studies with larger sample sizes are necessary to confirm our findings., Competing Interests: The authors declare no conflict of interest, financial or otherwise., (© 2024 Bentham Science Publishers.)

Extracellular vesicles (EVs) are nano-sized, membranous structures secreted into the extracellular space. They exhibit diverse sizes, contents, and surface markers and are ubiquitously released from cells under normal and pathological conditions. Human serum is a rich source of these EVs, though their isolation from serum proteins and non-EV lipid particles poses challenges. These vesicles transport various cellular components such as proteins, mRNAs, miRNAs, DNA, and lipids across distances, influencing numerous physiological and pathological events, including those within the tumor microenvironment (TME). Their pivotal roles in cellular communication make EVs promising candidates for therapeutic agents, drug delivery systems, and disease biomarkers. Especially in cancer diagnostics, EV detection can pave the way for early identification and offers potential as diagnostic biomarkers. Moreover, various EV subtypes are emerging as targeted drug delivery tools, highlighting their potential clinical significance. The need for non-invasive biomarkers to monitor biological processes for diagnostic and therapeutic purposes remains unfulfilled. Tapping into the unique composition of EVs could unlock advanced diagnostic and therapeutic avenues in the future. In this review, we discuss in detail the roles of EVs across various conditions, including cancers (encompassing head and neck, lung, gastric, breast, and hepatocellular carcinoma), neurodegenerative disorders, diabetes, viral infections, autoimmune and renal diseases, emphasizing the potential advancements in molecular diagnostics and drug delivery., (© 2024. The Author(s).)

The advent of nanotechnology has been instrumental in the development of new drugs with novel targets. Recently, metallic nanoparticles have emerged as potential candidates to combat the threat of drug-resistant infections. Diabetic foot ulcers (DFUs) are one of the dreadful complications of diabetes mellitus due to the colonization of numerous drug-resistant pathogenic microbes leading to biofilm formation. Biofilms are difficult to treat due to limited penetration and non-specificity of drugs. Therefore, in the current investigation, SnO 2 nanoparticles were biosynthesized using Artemisia vulgaris (AvTO-NPs) as a stabilizing agent and were characterized using ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). Furthermore, the efficacy of AvTO-NPs against biofilms and virulence factors of drug-resistant Candida albicans strains isolated from DFUs was assessed. AvTO-NPs displayed minimum inhibitory concentrations (MICs) ranging from 1 mg/mL to 2 mg/mL against four strains of C. albicans. AvTO-NPs significantly inhibited biofilm formation by 54.8%-87%, germ tube formation by 72%-90%, cell surface hydrophobicity by 68.2%-82.8%, and exopolysaccharide (EPS) production by 69%-86.3% in the test strains at respective 1/2xMIC. Biosynthesized NPs were effective in disrupting established mature biofilms of test strains significantly. Elevated levels of reactive oxygen species (ROS) generation in the AvTO-NPs-treated C. albicans could be the possible cause of cell death leading to biofilm inhibition. The useful insights of the present study could be exploited in the current line of treatment to mitigate the threat of biofilm-related persistent DFUs and expedite wound healing., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zubair, Husain, Al-Amri, Hasan, Hassan, Albalawi, Fatima, Khan, Arshad, Alam, Ahmad, Alatawy, Begum, Mir, Alshadfan, Ansari and Al-Anazi.)

Seldom found in saltmarshes, Linum maritimum is a halophyte of great conservation interest in the eastern Iberian Peninsula. Although the species has been reported in different plant communities, there is no information on its range of salinity tolerance or mechanisms of response to environmental stress factors. In this study, L. maritimum plants were subjected to increasing salt concentrations in controlled conditions in a greenhouse. After six months of watering with salt solutions, only plants from the control, 50 mM and 100 mM NaCl treatment groups survived, but seeds were produced only in the first two. Significant differences were found between the plants from the various treatment groups in terms of their growth parameters, such as plant height, fresh weight, and the quantity of flowers and fruits. The main mechanism of salt tolerance is probably related to the species' ability to activate K + uptake and transport to shoots to partly counteract the accumulation of toxic Na + ions. A biochemical analysis showed significant increases in glycine betaine, flavonoids and total phenolic compounds, highlighting the importance of osmotic regulation and antioxidant compounds in the salt tolerance of Linum maritimum . These findings have implications for the conservation of the species, especially under changing climatic conditions that may lead to increased soil salinity in its Mediterranean distribution area.

Aim: To evaluate the associations of the pathogenic variants in Kruppel-like Factor 14 (KLF 14) and Adiponectin (ADIPOQ) with susceptibility to type 2 diabetes mellitus (T2DM)., Background: Type 2 diabetes mellitus (T2DM) is a pandemic metabolic disease characterized by increased blood sugar and caused by resistance to insulin in peripheral tissues and damage to pancreatic beta cells. Kruppel-like Factor 14 (KLF-14) is proposed to be a regulator of metabolic diseases, such as diabetes mellitus (DM) and obesity. Adiponectin (ADIPOQ) is an adipocytokine produced by the adipocytes and other tissues and was reported to be involved in T2DM., Objectives: To study the possible association of the KLF-14 rs972283 and ADIPOQ-rs266729 with the risk of T2DM in the Saudi population., Methods: We have evaluated the association of KLF-14 rs972283 C>T and ADIPOQ-rs266729 C>G SNV with the risk to T2D in the Saudi population using the Amplification Refractory Mutation System PCR (ARMS-PCR), and blood biochemistry analysis. For the KLF-14 rs972283 C>T SNV we included 115 cases and 116 healthy controls, and ADIPOQ-rs266729 C>G SNV, 103 cases and 104 healthy controls were included., Results: Results indicated that the KLF-14 rs972283 GA genotype and A allele were associated with T2D risk with OR=2.14, p-value= 0.014 and OR=1.99, p-value=0.0003, respectively. Results also ADIPOQ-rs266729 CG genotype and C allele were associated with an elevated T2D risk with an OR=2.53, p=0.003 and OR=1.66, p-value =0.012, respectively., Conclusion: We conclude that SNVs in KLF-14 and ADIPOQ are potential loci for T2D risk. Future large-scale studies to verify these findings are recommended. These results need further verifications in protein functional and large-scale case control studies before being introduced for genetic testing., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Plasma-derived von Willebrand factor-containing factor VIII concentrates (pd-VWF/FVIII-C) are the mainstay of treatment in von Willebrand disease (VWD). Real-world data on efficacy and safety of these pd-VWF/FVIII-C are required. To retrospectively evaluate the efficacy and safety of pd-VWF/FVIII-C (Fanhdi® and Alphanate®, Grifols) in clinical practice in Italy. A multicentric, observational, retrospective study at 10 Italian centers was conducted. Eligible patients diagnosed with inherited VWD (ISTH criteria) were treated with either Fanhdi® or Alphanate® for bleeding episodes, prevention of surgical bleeding and secondary long-term prophylaxis (SLTP) according to clinical practice with medical records collected from January 2007 to December 2019. Efficacy/safety of pd-VWF/FVIII-C was assessed according to FDA-agreed objective criteria following regulatory procedures. Fifty-seven patients (M/F: 21/36) were enrolled in the study with the following VWD types: VWD1 (n = 29, 52%), VWD2A (n = 10, 18%), VWD2B (n = 7, 12%), VWD2M (n = 2, 4%), VWD2N (n = 1, 2%), VWD2 unclassified (n = 1, 2%), and VWD3 (n = 7, 12%). These pd-VWF/FVIII-C were used to manage 58 bleeding episodes (n = 24 patients), 100 surgeries (n = 47 patients), and 7 SLTP (n = 6 patients). Global clinical efficacy with these pd-VWF/FVIII-C was reported to be excellent/good in 85% of bleeding episodes, 98% of surgeries, and 100% of SLTP. As far as safety, no adverse-drug-related episodes, immunogenic or thrombotic events were reported. This study confirmed that Fanhdi® and Alphanate® were effective and safe in the management of bleeding episodes, the prevention of bleeding during surgeries and for SLTP in Italian patients with inherited VWD., Competing Interests: Declaration of Conflicting InterestsR. Mir is full-time employee of Grifols. E. Mairal is a former full-time employee of Grifols. A.B. Federici has been involved in advisory boards of Baxalta/Shire/Takeda, CSL Behring, Grifols, Kedrion, LFB and Octapharma with honoraria related to VWD. The remaining authors declare that there is no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The climatic changes have great threats to sustainable agriculture and require efforts to ensure global food and nutritional security. In this regard, the plant strategic responses, including the induction of plant hormones/plant growth regulators (PGRs), play a substantial role in boosting plant immunity against environmental stress-induced adversities. In addition, secondary metabolites (SMs) have emerged as potential 'stress alleviators' that help plants to adapt against environmental stressors imposing detrimental impacts on plant health and survival. The introduction of SMs in plant biology has shed light on their beneficial effects in mitigating environmental crises. This review explores SMs-mediated plant defense responses and highlights the crosstalk between PGRs and SMs under diverse environmental stressors. In addition, genetic engineering approaches are discussed as a potential revenue to enhance plant hormone-mediated SM production in response to environmental cues. Thus, the present review aims to emphasize the significance of SMs implications with PGRs association and genetic approachability, which could aid in shaping the future strategies that favor agro-ecosystem compatibility under unpredictable environmental conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing conflict of interest or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Aim: To study if individuals with nocturnal gastroesophageal reflux (nGER) and habitual snoring are more likely to develop asthma and respiratory symptoms (i.e. wheeze, cough, chest tightness, breathlessness) than those without these conditions, and if these associations are additive., Methods: We used data from the population-based prospective questionnaire study Respiratory Health in Northern Europe (RHINE) (11,024 participants), with data from 1999 and 2011. Participants with heartburn or belching after going to bed, at least 1 night/week, were considered to have nGER. Participants reporting loud snoring at least 3 nights/week were considered to have habitual snoring. Participants were grouped into four groups by their nGER and snoring status: "never"; "former"; "incident"; "persistent". Incident respiratory symptoms were analyzed among participants without respective symptom at baseline., Results: Snoring and nGER were independently associated with incident asthma and respiratory symptoms. The risk of incident wheeze was increased in subjects with incident or persistent snoring (adjusted odds ratio (95 % CI): 1.44 (1.21-1.72)), nGER (2.18 (1.60-2.98)) and in those with both snoring and nGER (2.59 (1.83-3.65)). The risk of developing asthma was increased in subjects with incident or persistent snoring (1.44 (1.15-1.82)), nGER (1.99 (1.35-2.93)) and in those with both snoring and nGER (1.72 (1.06-2.77)). No significant interaction was found between snoring and nGER. A similar pattern was found for the incidence of all other respiratory symptoms studied, with the highest risk among those with both incident or persistent nGER and snoring., Conclusion: The risk of developing asthma and respiratory symptoms is increased among subjects with nGER and habitual snoring. These associations are independent of each other and confounding factors. Snoring and nGER together are additive on respiratory symptoms., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Coronary artery disease (CAD) is a major cause of death worldwide, and India contributes to about one-fifth of total CAD deaths. The development of CAD has been linked to the accumulation of Nε-carboxymethyl-lysine (CML) in heart muscle, which correlates with fibrosis., Aim: To assess the impact of CML and inflammatory markers on the biochemical and cardiovascular characteristics of CAD patients with and without diabetes., Methods: We enrolled 200 consecutive CAD patients who were undergoing coronary angiography and categorized them into two groups based on their serum glycosylated hemoglobin (HbA1c) levels (group I: HbA1c ≥ 6.5; group II: HbA1c < 6.5). We analyzed the levels of lipoproteins, plasma HbA1c levels, CML, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and nitric oxide., Results: Group I (81 males and 19 females) patients had a mean age of 54.2 ± 10.2 years, with a mean diabetes duration of 4.9 ± 2.2 years. Group II (89 males and 11 females) patients had a mean age of 53.2 ± 10.3 years. Group I had more severe CAD, with a higher percentage of patients with single vessel disease and greater stenosis severity in the left anterior descending coronary artery compared to group II. Group I also exhibited a larger left atrium diameter. Group I patients exhibited significantly higher levels of CML, TNF-α, and IL-6 and lower levels of nitric oxide as compared with group II patients. Additionally, CML showed a significant positive correlation with IL-6 ( r = 0.596, P = 0.001) and TNF-α ( r = 0.337, P = 0.001) and a negative correlation with nitric oxide ( r =-4.16, P = 0.001). Odds ratio analysis revealed that patients with CML in the third quartile (264.43-364.31 ng/mL) were significantly associated with diabetic CAD at unadjusted and adjusted levels with covariates., Conclusion: CML and inflammatory markers may play a significant role in the development of CAD, particularly in diabetic individuals, and may serve as potential biomarkers for the prediction of CAD in both diabetic and non-diabetic patients., Competing Interests: Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. All authors declare no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Plant nutrition is an important aspect that contributes significantly to sustainable agriculture, whereas minerals enrichment in edible source implies global human health; hence, both strategies need to be bridged to ensure "One Health" strategies. Abiotic stress-induced nutritional imbalance impairs plant growth. In this context, we discuss the molecular mechanisms related to the readjustment of nutrient pools for sustained plant growth under harsh conditions, and channeling the minerals to edible source (seeds) to address future nutritional security. This review particularly highlights interventions on (i) the physiological and molecular responses of mineral nutrients in crop plants under stressful environments; (ii) the deployment of breeding and biotechnological strategies for the optimization of nutrient acquisition, their transport, and distribution in plants under changing environments. Furthermore, the present review also infers the recent advancements in breeding and biotechnology-based biofortification approaches for nutrient enhancement in crop plants to optimize yield and grain mineral concentrations under control and stress-prone environments to address food and nutritional security., (© 2023 The Authors. The Plant Genome published by Wiley Periodicals LLC on behalf of Crop Science Society of America.)

Coronary artery disease (CAD) is the leading cause of death and hospitalization worldwide and represents a problem for public health systems everywhere. In Saudi Arabia, the prevalence of CAD is estimated to be 5.5%. Risk factors for CAD include older age, male gender, obesity, high blood pressure, smoking, diabetes, hyperlipidemia, and genetic factors. Reducing the risk factors in susceptible individuals will decrease the prevalence of CAD. Genome wide association studies have helped to reveal the association of many loci with diseases like CAD. In this study, we examined the link between single nucleotide variations (SNVs) of TNF-α-rs1800629 G>A, CYP2C19*17 (rs12248560) C>T, and miR-423 rs6505162 C>A and the expression of TNF-α with CAD. We used the mutation specific PCR, ARMS-PCR, and ELISA. The results showed that the A allele of the TNF-α rs1800629 G>A SNP is linked to CAD with odd ratio (OR) (95% CI) = 2.10, p -value = 0.0013. The T allele of the CYP2C19*17 (rs12248560) C>T is linked to CAD with OR (95% CI) = 2.02, p -value = 0.003. In addition, the A allele of the miR-423 rs6505162 C>A SNV is linked to CAD with OR (95% CI) = 1.49, p -value = 0.036. The ELISA results indicated that the TNF-α serum levels are significantly increased in CAD patients compared to healthy controls. We conclude the TNF-α rs1800629 G>A, CYP2C19*17, and miR-423 rs6505162 C>A are potential genetic loci for CAD in the Saudi population. These findings require further verification in future studies. After being verified, our results might be utilized in genetic testing to identify individuals that are susceptible to CAD and, therefore, for whom reducing modifiable risk factors (e.g., poor diet, diabetes, obesity, and smoking) would result in prevention or delay of CAD.

This study presents an exploration of the efficacy of brassinosteroids (BRs) and ethylene in mediating heat stress tolerance in rice (Oryza sativa). Heat is one of the major abiotic factors that prominently deteriorates rice production by influencing photosynthetic efficiency, source‒sink capacity, and growth traits. The application of BR (0.5 mM) and ethylene (200 μl l -1 ) either individually and/or in combination was found to alleviate heat stress-induced toxicity by significantly improving photosynthesis, source‒sink capacity and defense systems; additionally, it reduced the levels of oxidative stress markers and ethylene formation. The study revealed the positive influence of BR in promoting plant growth responses under heat stress through its interplay with ethylene biosynthesis and enhanced plant defense systems. Interestingly, treatment with the ethylene biosynthesis inhibitor aminoethoxyvinylglycine (AVG) substantiated that BR application to heat-stressed rice plants enhanced ethylene-dependent pathways to counteract the underlying adversities. Thus, BR action was found to be mediated by ethylene to promote heat tolerance in rice. The present study sheds light on the potential tolerance mechanisms which can ensure rice sustainability under heat stress conditions., Competing Interests: Declaration of competing interest Authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Type 2 diabetes (T2D) develops from insulin resistance (IR) and the dysfunction of pancreatic beta cells. The AKT2 protein is very important for the protein signaling pathway, and the non-synonymous SNP (nsSNPs) in AKT2 gene may be associated with T2D. nsSNPs can result in alterations in protein stability, enzymatic activity, or binding specificity. The objective of this study was to investigate the effect of nsSNPs on the AKT2 protein structure and function that may result in the induction of IR and T2D. The study identified 20 variants that were considered to be the most deleterious based on a range of analytical tools included (SIFT, PolyPhen2, Mut-pred, SNAP2, PANTHER, PhD-SNP, SNP&Go, MUpro, Cosurf, and I-Mut). Two mutations, p.A179T and p.L183Q, were selected for further investigation based on their location within the protein as determined by PyMol. The results indicated that mutations, p.A179T and p.L183Q alter the protein stability and functional characteristics, which could potentially affect its function. In order to conduct a more in-depth analysis of these effects, a molecular dynamics simulation was performed for wildtype AKT2 and the two mutants (p.A179T and p.L183Q). The simulation evaluated various parameters, including temperature, pressure, density, RMSD, RMSF, SASA, and Region, over a period of 100 ps. According to the simulation results, the wildtype AKT2 protein demonstrated higher stability in comparison to the mutant variants. The mutations p.A179T and p.L183Q were found to cause a reduction in both protein stability and functionality. These findings underscore the significance of the effects of nsSNPs (mutations p.A179T and p.L183Q) on the structure and function of AKT2 that may lead to IR and T2D. Nevertheless, they require further verifications in future protein functional, protein-protein interaction, and large-scale case-control studies. When verified, these results will help in the identification and stratification of individuals who are at risk of IR and T2D for the purpose of prevention and treatment.

The plant growth regulator, jasmonic acid (JA) has emerged as important molecule and involved in key processes of plants. In this study, we investigated the role of methyl jasmonate (MeJA) in achieving tolerance mechanisms against arsenic (As) stress in rice (Oryza sativa). Arsenic toxicity is a major global concern that significantly deteriorate rice production. The application of MeJA (20 μM) and ethylene (150 μL L -1 ) both individually and/or in combination were found significant in protecting against As-induced toxicity in rice, and significantly improved defense systems. The study shown that the positive influence of MeJA in promoting carbohydrate metabolism, photosynthesis and growth under As stress were the result of its interplay with ethylene biosynthesis and reduced oxidative stress-mediated cellular injuries and cell deaths. Interestingly, the use of JA biosynthesis inhibitor, neomycin (Neo) and ethylene biosynthesis inhibitor, aminoethoxyvinylglycine (AVG) overturned the effects of MeJA and ethylene on plant growth under As stress. From the pooled data, it may also be concluded that Neo treatment to MeJA- treated rice plants restricted JA-mediated responses, implying that application of MeJA modulated ethylene- dependent pathways in response to As stress. Thus, the action of MeJA in As tolerance is found to be mediated by ethylene. The study will shed light on the mechanisms that could be used to ensure the sustainability of rice plants under As stress., Competing Interests: Declaration of competing interest All authors have read and agreed to the published version of the manuscript. Authors have no conflicts., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Type 2 diabetes (T2D) is a metabolic condition induced by insulin resistance and pancreatic beta cell dysfunction. MicroRNAs (miRNAs) have biological significance because they regulate processes such as the molecular signaling pathways involved in the pathophysiology of diabetes mellitus. The hepatocyte nuclear factor-1 alpha (HNF-1 alpha) is a transcription factor found in hepatocytes and the pancreas. Mutations in the HNF-1 alpha gene were reportedly associated with maturity-onset diabetes of the young (MODY). The objective of the present study was to examine the associations between MiR-27a, MiR-146, and HNF-1 alpha single-nucleotide variations (SNVs) with T2D risk in the Saudi population., Methodology: We evaluated the association of SNVs of miR-27a rs895819 A>G, 146a-rs2910164 C>G, and HNF-1 alpha rs1169288 G>T (I27L) with the risk of T2D in Saudi patients with the Amplification Refractory Mutation System PCR (ARMS-PCR). For the miR-27a SNVs, we used 115 cases (82 males, 33 females) and 117 matched healthy controls (HCs); for the Mir-146 SNVs, we used 103 cases (70 males, 33 females) and 108 matched HCs; and for the HNF-1 alpha, we employed 110 patients (80 males, 30 females) and 110 HCs. The blood biochemistry of the participants was essayed using commercial kits, and the methods of statistical analysis used were the Chi-square test, the Fisher exact test, and a multivariate analysis based on logistic regression, like the odds ratio (OD) and risk ratio (RR), with 95% confidence intervals (CIs)., Results: The MiR-27a rs895819 AG genotype was linked to increased T2D susceptibility, with OR = 2.01 and p -value = 0.011, and the miR-146 rs2910164 CG genotype and C allele were linked to an elevated risk of T2D, with OR = 2.75, p -value < 0.0016, OR = 1.77, and p -value = 0.004. The results also showed that the GT genotype and T allele of the HNF-1 alpha (rs1169288) G>T is linked to T2D, with OR = 2.18, p -value = 0.0061, and 1.77, p -value = 0.0059., Conclusions: The SNVs in miR-27a, miR-146, and HNF-1 alpha can be potential loci for T2D risk. The limitations of this study include the relatively small sample size and the fact that it was a cross-sectional study. To our knowledge, this is the first study to highlight the association between miR-27a, miR-146, and HNF-1 alpha SNVs and the risk of T2D in the Saudi population. Future large-scale case-control studies, as well as studies on the functions of the proteins and protein interaction studies for HNF-1 alpha, are required to verify our findings. Furthermore, these findings can be used for the identification and stratification of at-risk populations via genetic testing for T2D-prevention strategies.

Objective: To assess the risk and prevalence of work-related musculoskeletal disorders (WMSDs) in spine and cranial surgeons., Methods: A cross-sectional analytic study composed of a risk assessment and a questionnaire-based survey was conducted. The risk assessment for WMSDs was performed on young volunteer neurosurgeons using the Rapid Entire Body Assessment tool. The survey-based questionnaire was distributed using the Google Forms software among the relevant official WhatsApp groups of the Egyptian Society of Neurological Surgeons and the Egyptian Spine Association., Results: Thirteen volunteers with a median service of 8 years were assessed for the risk of WMSDs, showing moderate to very high risk of WMSDs, with a Risk Index >1 for all assessed postures. A total of 232 respondents completed the questionnaire, 74% of whom reported WMSD symptoms. Pain was experienced by most (96%), with neck pain being the most common (62.8%), followed by low back pain (56.0%), shoulder pain (44.5%), and wrist/finger pain (43.9%). Pain was experienced for 1-3 years by most respondents; however, most did not reduce their case volume, seek medical advice, or stop working when they experienced pain. The survey showed shortage in the literature studying ergonomics, calling for more ergonomic education and furnishing of working environment of neurosurgeons., Conclusions: WMSDs are prevalent among neurosurgeons, affecting their ability to work. Ergonomics need further awareness, education, and interventions to reduce WMSDs, especially neck and low back pain, which proved to substantially interfere with work ability., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Compensatory sweating (CS) is a frequent health concern following treatment of palmar hyperhidrosis using video-assisted thoracoscopic sympathectomy (VATS) and can reduce level of patient satisfaction., Methods: A retrospective cohort study including consecutive patients who underwent VATS for primary palmar hyperhidrosis (HH) over a 5-year period was conducted. Various demographic, clinical, and surgical variables were tested for their correlation to postoperative CS through univariate analyses. Variables with significant correlation to outcome were included in a multivariable logistic regression for determining significant predictors., Results: The study included 194, predominantly male (53.6%), patients. About 46% of patients developed CS, mostly during the first month after VATS. Variables with significant correlation (P < 0.05) to CS included age (20 ± 3.6 years), body mass index (BMI) (mean 27 ± 4.9), smoking (34%), associated plantar HH (50%), and laterality of VATS (40.2% in dominant side). Only level of activity showed a statistical trend (P = 0.055). In multivariable logistic regression, BMI, plantar HH, and unilateral VATS were significant predictors for CS. Using receiver operating characteristic curve, the best cutoff point of BMI for prediction was 28.5, with sensitivity 77% and specificity 82%., Conclusions: CS is a frequent health concern early after VATS. Patients with BMI >28.5 and no plantar HH are at higher risk of postoperative CS, and a unilateral dominant side VATS as an initial management step may lessen the risk of CS. Bilateral VATS can be provided for patients with low risk of CS and patients with low satisfaction after unilateral VATS., (Copyright © 2023 Elsevier Inc. All rights reserved.)