Minia University

Scopolamine, a muscarinic receptor antagonist, is widely utilized to pharmacologically model Alzheimer’s disease (AD) due to its ability to mimic cholinergic deficits and induce memory impairments. Despite its common use in investigating behavioral and cognitive impairments in memory deficit animal models, the longitudinal brain-wide electrophysiological alterations associated with scopolamine administration remain largely unexplored. This study integrated electrophysiological and behavioral analyses to investigate scopolamine-induced cognitive deficits in mice. Using a 16-channel intracranial electroencephalography (iEEG) array, we tracked brain-wide oscillatory changes and functional connectivity over 6 weeks during memory task-related and task-free activities. The mouse’s pre-attentive sensory memory was assessed by auditory evoked potentials (AEPs) within the passive oddball mismatch negativity (MMN) paradigm, and the mouse’s spatial working memory was further evaluated using a Y-maze spontaneous alternation task. The auditory MMN responses indicated significant sensory discrimination impairments from Week 2 onward, and spontaneous theta oscillations demonstrated widespread disruptions by Week 3. Concurrently, scopolamine degraded the animal’s Y-maze successful alternation rates. The decline in alternation performance was correlated with the observed electrophysiological alterations, revealing the progressive impact of scopolamine on cognitive and neural functions. Furthermore, this study identified early electrophysiological biomarkers of brain functional network changes associated with memory impairments, in which functional connectivity abnormalities were observed from the first week of scopolamine administration, suggesting they have diagnostic potential in preclinical AD research. By bridging behavioral outcomes with brain-wide iEEG metrics, this work emphasizes the translational relevance of scopolamine models for understanding AD-like pathology and evaluating therapeutic interventions.

The green synthesis of metal oxide nanoparticles has emerged as a sustainable and eco-friendly alternative to conventional chemical methods. Utilizing plant-derived phytochemicals as natural reducing and stabilizing agents, this approach eliminates hazardous chemicals and energy-intensive processes. Beyond environmental benefits, green synthesis influences the physicochemical and biological properties of nanoparticles by enhancing surface functionality, stability, and bioactivity. Zinc oxide nanoparticles are widely favored in biomedical applications due to their biocompatibility, affordability, and low toxicity. Their therapeutic effects, especially in anticancer and antibacterial applications, arise from their ability to generate reactive oxygen species, release Zn²⁺ ions, and induce apoptosis. This study synthesized ZnO NPs via chemical and green routes using aqueous extracts from Medicago sativa, Euphorbia milii, Codiaeum variegatum, and Helianthus annuus. Structural analysis confirmed that green synthesis did not alter the ZnO crystalline structure. However, biological activities varied significantly by plant extract. Codiaeum variegatum-mediated ZnO NPs showed superior antioxidant activity (60.8% DPPH scavenging) and strong cytotoxicity against A549 lung cancer cells (94.7% reduction). Chemically synthesized ZnO NPs exhibited notable anti-inflammatory activity (90.4%). ZnO NPs from Medicago sativa demonstrated potent antidiabetic effects via α-amylase (86.5%) and α-glucosidase (85.7%) inhibition. All ZnO NPs inhibited the growth of Escherichia coli, Klebsiella pneumonia, Streptococcus pyrogenes, and Staphylococcus aureus with maximum MBC value 47.4 mg/ml of chemogenic ZnO NPs against S. aureus and 44.4 mg/ml for biogenic ZnO NPs against S. pyrogenes. Additionally, Medicago sativa ZnO NPs recorded the highest suppression of S. pyogenes biofilm formation by 79%. The obtained results highlight the role of green synthesis as an effective strategy to tailor ZnO NP bioactivity for biomedical applications.

Erythrosine B (EB) is a food colorant and antiviral xanthene dye that is widely used as a color additive in pharmaceutical and cosmetic industries. Its application as a sensor for spectrophotometric measurement of amine-based pharmaceuticals offers several benefits due to its availability, low cost, quick labeling, and high sensitivity. In the present study, a quick, sensitive and simple green spectrophotometric method has been developed to assay Bromhexine Hydrochloride (BMH) in pure form and its pharmaceutical formulation. The spectrophotometric methodology reveals complex development between the drug and erythrosine B at 556 nm at pH 3.6. The spectrophotometric absorbance-concentration curve is linear over the ranges (1.0–9.0 μg mL⁻¹) with low detection limit 0.199 μg mL⁻¹ and low quantification limit 0.605 μg mL⁻¹. The developed approach was assessed for linearity, accuracy, precision, limits of detection, and limits of quantitation in compliance with International Council for Harmonisation validation recommendations. Lastly, the suggested approach has been successfully implemented to quantify the cited medication colorimetrically in its dosage form with excellent recoveries. Also, the greenness of the suggested approach was measured by some of the recent green analytical measures as applications to our presented methodology show further access to this study.

Natural pigments and dyes provide a rich interface between biodiversity and chemistry, offering structurally diverse molecules with distinctive reactivity and bioorganic relevance. These compounds occur in plants, marine organisms, fungi, bacteria, insects, birds, animals, and mineral sources. They encompass major chemical classes such as carotenoids, tetrapyrroles and their degradation products. Owing to their biocompatibility and natural origin, these pigments are increasingly explored as safer alternatives to synthetic dyes and as functional ingredients in food, cosmetic, textile, and pharmaceutical applications. In recent years, these natural pigments have gained significant attention as bioactive molecules with antioxidant, anti-inflammatory, antimicrobial, antiviral, anticancer, neuroprotective, hepatoprotective, and immunomodulatory potential, exhibiting beneficial effects in preventing chronic disorders like diabetes, cardiovascular and degenerative eye diseases. This review provides an integrated examination of biodiversity, chemical classes, biosynthetic logic, structure–activity relationships, and biological properties of these natural pigments and dyes. Key challenges related to chemical stability, bioavailability, and scalable production are discussed, together with emerging biotechnological strategies designed to enhance their stability and sustainable supply.

A series of new pyrazole/quinoline hybrids 11a–n was constructed and synthesized as prospective antiproliferative agents. The antiproliferative activities of the newly synthesized hybrids were assessed against a panel of four human cancer cells: HT‐29, A‐549, Panc‐1, and MCF‐7. Hybrids 11c, 11d, 11h, 11i, and 11k demonstrated remarkable antiproliferative activity, with IC50 ranging from 36 to 61 nM, compared to erlotinib, which had IC50 ranging from 30 to 40 nM. Hybrid 11i was the most potent EGFR inhibitor with an IC50 of 87 nM and exhibited comparable EGFR inhibition to that of erlotinib (IC50 = 80 nM). Molecular docking study results in the EGFR active site agreed with the EGFR inhibitory activity results.

Mandibular deficiency correction demands precise control of both advancement and rotation to achieve optimal function and facial harmony. The Barakat modification introduces an intraoral adaptation of the inverted L osteotomy, which enables simultaneous mandibular advancement and controlled counterclockwise rotation, eliminating the need for grafting and reducing morbidity. Cephalometric evaluation demonstrated consistent forward mandibular repositioning (mean SNB increase ≈ +1 degree) accompanied by reductions in FMA (≈ −3 to −5 degrees) and gonial angle (≈ −2 to −4 degrees), confirming effective rotational control with vertical shortening. Postoperative assessments revealed a stable occlusion, accurate bony alignment, and enhanced lower facial proportions, with no complications. The Barakat modification offers a predictable, minimally invasive solution for managing mandibular deficiency, combining advancement precision with rotational control to deliver superior aesthetic and functional outcomes.

Background This article aims to summarize the current recommended methods, guidelines and consensus among a panel of international experts meeting at the 16th Congress of the International Federations for Societies for Surgery of the Hand in 2025 and discussion prior to or after the congress in the tendon study group. Primary flexor tendon repair The updated guidelines and consensus emphasize (1) the use of strong and solid repair methods and true early active flexion in all flexor tendon repairs in zone 2, and also in zones 3–5, (2) no traditional running peripheral sutures when a six-strand repair is used, (3) not placing the knots between two tendon stumps, as the knots are foreign bodies and (4) abandoning place-and-hold exercise after surgery. Outcomes from the surgical units of these authors are reported to support these guidelines. Secondary flexor tendon reconstruction This article also summarizes guidelines relating to secondary reconstruction of the flexor tendons. We collectively suggest one-stage tendon grafting for the patients without a lengthy destruction of the pulleys – that is – not needing pulley reconstruction. Staged tendon grafting should be reserved for patients who require pulley reconstruction in the first stage. Early active motion can be used after such one-stage tendon grafting procedures. Conclusions Despite significant advances in flexor tendon repair and reconstruction, the drive towards perfection continues. The authors draw attention to outcomes obtained across the globe in recent years and highlight critical areas and pertinent technical points that the readers may use to improve their outcomes.

Benign prostatic hyperplasia (BPH) is a noncancerous prostate enlargement that significantly impacts the quality of life in aged men. Both oxidative stress and inflammation interplay to induce hyperplasia of prostatic epithelial cells as well as seminal vesicle tissues. Dihydromyricetin (DHM), extracted from Ampelopsis grossedentata, is used in traditional Chinese medicine for hundreds of years. It exhibited prominent anticancer, anti-inflammatory, and antioxidant activities in several models. To date, its potential protective effects for BPH have not been investigated. The aim of this study was to investigate the role of DHM in the management of testosterone-induced proliferation in prostate and seminal vesicle tissues. Male Wistar rats (200 to 250 g) were divided into three groups: a control group receiving sesame oil (the vehicle), a BPH group receiving testosterone oenanthate (3 mg/kg, subcutaneously) daily for 4 weeks to induce hyperplasia, and a DHM group receiving DHM (50 mg/kg) alongside testosterone oenanthate (3 mg/kg). DHM significantly reduced the prostate and seminal vesicle weights, ameliorated the histopathological changes induced by testosterone, and nearly normalized the serum testosterone, FSH, and LH levels. It also reduced the serum PSA level. Further, DHM reduced MDA levels while increasing GSH levels. Besides, it reduced the prostatic levels of 5-alpha reductase and attenuated TGF-β1/Smad-2 pathway. The anti-hyperproliferation and the anti-inflammatory effects of DHM were attributed to the attenuation of the expression of PCNA, procaspase-3, iNOS, TLR-4, and IL-1β in both the prostate and seminal vesicle tissues. DHM has potential protective effects against testosterone-induced BPH model via downregulation of inflammatory mediators, restoration of oxidative balance, and induction of cell apoptosis. Graphical Abstract

Pulmonary hypertension (PH) is a serious and potentially life-threatening complication of systemic lupus erythematosus (SLE). Its etiology in SLE is heterogeneous and includes vasculopathy, interstitial lung disease (ILD), left-sided heart dysfunction, and chronic thromboembolic disease. High-resolution computed tomography (HRCT) plays an important role in defining phenotypes and supporting targeted management. This analytical cross-sectional study included 60 adults with SLE and echocardiograph-confirmed PH. All patients underwent clinical evaluation and HRCT. Radiologic patterns were evaluated and correlated with pulmonary hypertension subtypes based on the 2022 ESC/ERS classification. We used SPSS v20 to analyze the data, and chi-square and Fisher’s exact tests were used to look for connections. In our cohort of patients with SLE and confirmed pulmonary hypertension, the most prevalent subtype observed was Group 2 PH, attributed to underlying left-sided heart disease (48.3%). This was followed by pulmonary arterial hypertension (25%), PH due to lung disease/hypoxia (20%), and chronic thromboembolic PH (6.7%). HRCT findings differed significantly among PH groups using Fisher’s Exact Test (p < 0.05). Normal HRCT scans were most frequent in Group 1, lung congestion with septal thickening predominated in Group 2 (p = 0.049), nonspecific interstitial pneumonia (NSIP)—a pattern of interstitial lung disease—was strongly associated with Group 3 (p < 0.000001), and all Group 4 patients demonstrated pulmonary embolism on Computed Tomography Pulmonary Angiography (CTPA) (p < 0.00001). HRCT patterns vary markedly across PH subtypes in SLE and provide important diagnostic clues to the underlying pathophysiological mechanism. HRCT provides important phenotypic information that supports noninvasive classification of SLE-associated pulmonary hypertension and helps guide further diagnostic and management pathways.

A green, sustainable, and highly sensitive fluorimetric method was developed for the quantitative determination of the antidiabetic agents alogliptin, saxagliptin, and vildagliptin in bulk powders and commercial formulations. The assay relies on charge–transfer complexation with fluorescein in acetate buffer at drug‐specific pH values, producing enhanced fluorescence at 513 nm ( λ ex = 470 nm). Under optimized conditions, linear responses were obtained within 2.00–50.00 μg/mL for saxagliptin, 1.00–30.00 μg/mL for vildagliptin, and 1.00–31.25 μg/mL for alogliptin, with detection limits of 0.54, 0.27, and 0.23 μg/mL, respectively. The corresponding quantification limits were 1.63, 0.81, and 0.70 μg/mL. The method exhibited excellent correlation coefficients across all ranges and was validated in accordance with ICH guidelines. Application to pharmaceutical tablets yielded results consistent with reported reference methods, confirming accuracy and precision without significant statistical differences. Greenness and sustainability were evaluated using multiple assessment tools (AGSA, GAPI, AGREE, MoGAPI, Eco‐scale, CACI, BAGI, CaFRI, and MA tool), confirming the eco‐friendly profile of the assay. The proposed method provides a reliable, green alternative for routine quality control of gliptins in pharmaceutical preparations.

Purpose This in vitro study compared initial retention forces and long‐term degradation patterns of three attachment systems for mandibular implant‐retained overdentures: solitary studs, milled bars with sleeves, and milled bars with studs. Materials and Methods A simulated mandibular model with three parallel implants received overdentures incorporating each attachment system (n = 10 per group). To simulate 5 years of clinical use, specimens underwent 5400 insertion‐removal cycles. Measurement of retention forces via vertical dislodgement (5 mm/min) was checked at 12 intervals. Statistical analysis included two‐way repeated measures ANOVA and linear regression to study retention degradation patterns. Results Two‐way repeated measures analysis of variance (ANOVA) revealed significant differences in retention stability (p<0.001). Bar systems demonstrated better durability, with bar‐sleeves keeping 16.03 ± 0.22 N (86.5% loss) and bar‐studs 19.90 ± 0.97 N (82.2% loss) after 5,400 cycles, compared to solitary studs’ 5.38 ± 0.21 N (95.8% loss). Linear regression confirmed predictable degradation in bar systems (R ² >0.84, slope: ‐7.23 to ‐7.03 N/cycle) versus erratic decay in solitary studs (R ² = 0.46). Post‐hoc tests showed no significant difference between bar subtypes (p = 0.567). Conclusion These findings suggest that, under in vitro conditions, splinted bar attachments, regardless of interface design, offer greater long‐term retention durability than solitary systems, considering their use may be advantageous in adequate prosthodontic space. The predictable linear degradation pattern of bar systems in this in vitro model suggests a potential mechanical rationale for less frequent maintenance (e.g., clip/matrix replacement every 3–4 years), in contrast to the more rapid and erratic degradation observed for solitary studs, which would imply a need for more frequent intervention in a clinical setting.

Background Migraine is a chronic, disabling brain disorder. Melatonin, a circadian regulator with anti-inflammatory and antinociceptive actions, has been proposed for migraine prevention. We evaluated the efficacy and safety of melatonin for prophylaxis. Methods We systematically searched PubMed, Cochrane, Scopus, Embase, and Web of Science (September 29, 2024) for randomised controlled trials (RCTs) comparing melatonin with placebo or other active drugs. Outcomes were analysed as change from baseline to last follow-up using mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI). Results Nine RCTs (n = 788) were included. Versus placebo, melatonin reduced attack duration (MD -4.98 h; 95% CI -9.30 to -0.67; p = 0.02), headache days (MD -1.54 days; 95% CI -2.50 to -0.58; p < 0.01), headache severity (MD -2.08; 95% CI -2.91 to -1.26; p < 0.01), and analgesic use (MD -1.38; 95% CI -2.41 to -0.36; p < 0.01). Melatonin also increased the response rate (≥ 50% reduction in monthly headache frequency) (RR 1.38; 95% CI 1.11–1.70; p < 0.01) and improved sleep quality (PSQI: MD -1.64; 95% CI -2.85 to -0.42; p = 0.008) and disability (MIDAS: SMD − 4.07; 95% CI -5.45 to -2.69; p < 0.001). Compared with amitriptyline, melatonin was generally less effective for attack duration and severity, with no consistent advantage on analgesic use or response; however, melatonin showed a more favourable tolerability profile, including lower risk of sleepiness (RR 0.49; 95% CI 0.28–0.87; p = 0.01). Conclusions Melatonin demonstrates benefits over placebo for reducing migraine burden and improving patient-reported outcomes, with a favourable safety profile. While amitriptyline remains more potent for several efficacy endpoints, melatonin represents a reasonable preventive option, particularly as an adjunct during titration of first-line agents. Further head-to-head trials with standardised dosing and longer follow-up are warranted.

This study investigated lacosamide (LCM), a third-generation antiepileptic drug, as a potential gonadoprotective agent against cyclophosphamide (CP)-induced testicular injury. The research addressed the critical need for safer antiepileptic alternatives in cancer patients requiring concurrent chemotherapy and seizure control. Male Wistar rats underwent comprehensive biochemical and histopathological analyses including Western blot, quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemistry, steroidogenic enzyme activity assessments, sexual hormone measurements, sperm quality evaluations, and molecular docking studies to evaluate LCM's protective mechanisms against CP-induced testicular damage. CP administration significantly elevated oxidative stress markers, pro-inflammatory mediators (Nuclear factor kappa B [NF-κB], Tumor necrosis factor-α [TNF-α], Interleukin-6 [IL-6], Interleukin-1β [IL-1β]), and apoptotic signaling (Bcl-2-associated x protein [Bax], caspase-3), while activating regulatory proteins c-jun N-terminal kinase 1 (JNK1) and Signal transducer and activator of transcription 3 (STAT-3) (identified as novel markers in CP-induced testicular injury). CP suppressed antioxidant defenses, steroidogenic factors (steroidogenic acute regulatory protein [StAR], 3β-hydroxysteroid dehydrogenase [3β-HSD], 17β-hydroxysteroid dehydrogenase [17β-HSD]), Heme oxygenase 1 (HO-1) expression, and androgen receptor (AR) functionality, resulting in decreased testosterone, gonadotropin levels, and compromised spermatogenesis. LCM treatment effectively mitigated these deleterious effects through multi-target protective mechanisms including c-jun N-terminal kinase 1(JNK1)-mediated apoptosis inhibition, HO-1 upregulation, IL-6/ signal transducer and activator of transcription 3 (STAT-3) signaling suppression, prevention of p-JNK1/STAT-3 crosstalk, and AR preservation. This study establishes LCM's multi-target protective efficacy, supporting its potential as a safer antiepileptic alternative providing dual benefits of seizure control and reproductive preservation during chemotherapy. Graphical Abstract

Objective Brain injury and neurodegenerative conditions are largely caused by oxidative damage and endoplasmic reticulum (ER) stress spurred on by hyperlipidemia. To lessen these consequences in the brains of hyperlipidemic rats, this study assesses the therapeutic potential of both rosuvastatin glycerosomes (RSV GLSMs) and niacin. Methods The study had five groups: control, hyperlipidemia induced by poloxamer 407 (P407), RSV GLSMs, niacin, or a combination of RSV GLSMs and niacin. Serum samples were collected for lipid profile assessment, whereas brain tissues were harvested for Reverse Transcription Polymerase Chain Reaction, histopathological, and immunohistochemical analyses. Results The treatment of P407 significantly decreased high-density lipoprotein and increased serum triglycerides, although RSV GLSMs and niacin substantially mitigated these changes. Malondialdehyde also surged in P407 rats, and total antioxidant capacity was diminished. RSV GLSMs and niacin supplementation significantly improved antioxidative defenses, with the combination therapy exhibiting more pronounced effects. RSV GLSMs and niacin notably lessen ER stress–responsive gene expression, including Eukaryotic Initiation Factor 2 alpha (eIF2α), C/EBP Homologous Protein (CHOP), X-box Binding Protein 1 (XBP1), c-Jun N-terminal Kinase (JNK), Binding Immunoglobulin Protein (BIP), and Activating Transcription Factor 6 (ATF-6) levels. In addition, RSV GLSMs and niacin improved autophagy by downregulating the Mammalian Target of Rapamycin (mTOR) and p62, and upregulating Beclin1 and Microtubule-associated protein 1A/1B-light chain 3, type II (LC3-II). According to immunohistochemical findings, RSV GLSMs and niacin reduced reactive gliosis and modulated the expression of B-cell lymphoma 2/Bcl-2-associated X protein (Bcl-2/Bax). Histopathological findings exhibited improved brain morphology, reduced vacuolization, and normalized glial cell distribution in the RSV GLSMs and niacin combination group, closely resembling the control group. Conclusions Overall, RSV GLSMs and niacin effectively mitigate hyperlipidemia-induced brain damage by modulating oxidative stress, ER stress, and autophagy pathways, suggesting potential as a promising treatment strategy.

Effective root canal disinfection is a critical component of predictable root canal treatment, yet obstacles remain in completely eradicating bacterial biofilms from the entire root canal system. Recent advances in instrument design, such as flat-side instruments, have been proposed to improve root canal disinfection and debridement. While conventional rotary instruments have been thoroughly evaluated, there is a paucity of data on the effectiveness of flat-side multi-file rotary systems in reducing the microbial burden within root canals. Therefore, this exploratory laboratory study was designed to assess the influence of the flat-side design in a full-sequence rotary file system on root canal disinfection compared to its conventional counterpart, aiming to establish initial data to guide further larger-scale research with more holistic microbial evaluations. Thirty mandibular first molars were selected according to specific criteria. After establishing an access cavity and ensuring root canal patency in all samples, the teeth underwent a cycle of autoclave sterilization. Enterococcus faecalis suspension was introduced into the root canals and incubated at 37 °C for 21 days. After bacterial contamination, an initial bacterial sampling (S1) was taken, and the specimens were distributed into 2 experimental groups according to the instrument design (n = 10 per group): flat-side full-sequence rotary files group (FS group); and its conventional prototype file system (CP group), along with positive and negative control groups (n = 5). At the end of the root canal preparation, another bacterial sampling (S2) was performed to determine the number of colony-forming units per mL (CFU//mL), and the results were compared with a robust ANOVA and the Games-Howell post hoc test with the significance level set at 5% and a confidence interval of 95%. None of the tested endodontic instruments succeeded in completely eradicating the root canal infection. However, the flat-side instruments showed a significant reduction in bacterial load, achieving a mean value of 2.78 ± 0.11, compared to their prototype counterparts, which had a higher mean bacterial load of 3.77 ± 0.32 (p-value < 0.05). Instrument design can affect root canal disinfection. Flat-side instruments may be more effective in reducing the bacterial burden from root canals than their traditional counterparts. However, this conclusion was derived from a preliminary investigation conducted under specific conditions. Therefore, to enhance the reliability and generalizability of the current outcomes, it is crucial to conduct further investigations with an adequate sample size across diverse laboratory and clinical settings, as well as variations in root canal morphology, to provide a more comprehensive understanding of the impact of this design on root canal infection. The present preliminary findings suggest that while complete elimination of infection remains challenging, advancements in instrument design, such as the flat-side instruments, could enhance bacterial reduction within root canals.

Theoretical models of prebiotic evolution propose that catalytic modulation can influence autocatalytic replication cycles. We hypothesized that a protein catalyst could create a favorable environment for proximity‐controlled, dissipative replication of primitive peptides. This setup, in principle, allows competitive selection by making the catalyst a limited resource. Here, we show that a structurally flexible and promiscuous protein, calmodulin, catalyzes UVA light‐driven replication in a helical foldamer‐based replicator system. The protein accelerates both non‐autocatalytic synthesis and autocatalytic replication, with autocatalysis being the dominant pathway. The system demonstrates light‐intensity‐dependent competitive selection, where replicators compete for scarce binding sites on the catalyst. This mechanism enables efficient selection even within a large replicator pool. Our results provide evidence that the specific catalyst–replicator interactions envisioned in Eigen's hypercycle model can be approximated under dissipative conditions in catalyzed primitive replicator systems.

Theoretical models of prebiotic evolution propose that catalytic modulation can influence autocatalytic replication cycles. We hypothesized that a protein catalyst could create a favorable environment for proximity‐controlled, dissipative replication of primitive peptides. This setup, in principle, allows competitive selection by making the catalyst a limited resource. Here, we show that a structurally flexible and promiscuous protein, calmodulin, catalyzes UVA light‐driven replication in a helical foldamer‐based replicator system. The protein accelerates both non‐autocatalytic synthesis and autocatalytic replication, with autocatalysis being the dominant pathway. The system demonstrates light‐intensity‐dependent competitive selection, where replicators compete for scarce binding sites on the catalyst. This mechanism enables efficient selection even within a large replicator pool. Our results provide evidence that the specific catalyst–replicator interactions envisioned in Eigen's hypercycle model can be approximated under dissipative conditions in catalyzed primitive replicator systems.

This study aimed to detect the changes in certain immunological parameters and miRNAs in COVID-19 cases with various degrees of disease severity and compare these changes in cases to healthy controls. This study was conducted on 45 COVID‐19 patients and 45 healthy controls. The flow cytometry was conducted to study the number of CD4 + and CD8 + T cells and evaluate the level of the PD-1 marker on their surfaces for all study participants. The determination of IL-1β and IL-6 in serum for all study subjects was done by ELISA test. Relative gene expression quantitation of miR-146a and miR-133a was performed by reverse transcriptase real-time PCR (RT-PCR). The numbers of CD4 + and CD8 + T cells were dramatically reduced in COVID-19 patients, especially in severe to critical patients, with an increase in the CD4 + :CD8 + ratio. T cells from COVID-19 patients had significantly higher levels of the exhausted marker PD-1. Measurement of IL-1β and IL-6 serum levels among cases group showed a highly significant increase in their mean concentration levels in comparison with the control group. Studying the difference in serum levels of IL-1β and IL-6 among different degrees of disease severity showed a significant decrease in their mean concentration levels among the mild to moderate group in comparison with the severe to critical group. The results also showed a significant decrease in miR-146a and a significant increase in miR-133a expression in COVID-19 patients compared to healthy controls. Reduced T cell counts, increased CD4 + :CD8 + ratio, higher levels of the PD-1 marker, elevated serum levels of the pro-inflammatory cytokines, and decreased miR-146a and increased miR-133a gene expressions could be used as potential markers in the assessment of COVID-19 infection and severity.

The advent of advanced technologies such as blockchain (BC), artificial intelligence (AI), big data, and the internet of things (IoT) promises a transformative era in healthcare. BC offers solutions to critical healthcare challenges including data interoperability, security, and patient privacy, due to its decentralized, secure, and transparent nature. Networking IoT devices through BC provides seamless and secure connectivity for continuous patient monitoring and management. Integrating big data analytics ensures the integrity and security of massive health datasets, fostering trust and compliance with regulatory standards. AI-driven analytics and predictive modeling can harness large datasets for early disease detection and personalized treatment plans. Combining BC with these technologies enhances data accuracy, facilitates real-time monitoring for patients, and improves decision-making processes in healthcare delivery. To achieve these objectives, this paper employs a systematic literature review methodology, covering publications indexed in Scopus, Web of Science, and PubMed between 2017 and late 2024. The study selection followed clear inclusion and exclusion criteria to ensure the relevance and quality of analyzed research. This paper studies recent literature to understand the extent and impact of these technologies on healthcare systems. It examines the progress and challenges of applying BC, AI, Big Data, and IoT within healthcare systems. The study identifies emerging trends, collaboration patterns, and key areas for future use and investigation. The findings highlight the necessity for integrated technological frameworks to address the evolving demands of healthcare, ensuring better health outcomes, enhanced patient experiences, and optimized resource utilization.