Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. In particular, the modRNA-based COVID-19 vaccines have proven that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options. MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and improves cardiac dysfunction. However, it remains elusive whether the early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. To obtain acute CCN5 expression, we used modRNA-mediated gene transfer in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: 1) preventive intervention and 2) therapeutic intervention. Cardiac function and structural changes were measured by echocardiography and magnetic resonance imaging. Finally, fibrosis and the underlying molecular pathway were analyzed by western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. The modRNA-CCN5 gene transfer successfully ameliorated CF and enhanced cardiac function in both preventive and therapeutic interventions without LV rupture or any adverse cardiac remodeling. Conclusively, early intervention in CF by modRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure without adverse structural remodeling.

Mitochondria are dynamic organelles that can adjust and respond to different stimuli within a cell. This plastic ability allows them to effectively coordinate several cellular functions in cells and becomes particularly relevant in highly complex cells such as neurons. An imbalance in mitochondrial dynamics can disrupt mitochondrial function, leading to abnormal cellular function and ultimately to a range of diseases, including neurodegenerative disorders. Regulation of mRNA transport and local translation inside neurons is crucial for maintaining the proteome of distal mitochondria, which is vital for energy production and synaptic function. A significant portion of the axonal transcriptome is dedicated to mRNAs for mitochondrial proteins, emphasizing the importance of local translation in sustaining mitochondrial function in areas far from the cell body. In neurons, local translation and the regulation of mRNAs encoding mitochondrial-shaping proteins could be essential for synaptic plasticity and neuronal health. The dynamics of these mRNAs, including their transport and local translation, may influence the morphology and function of mitochondria, thereby affecting the overall energy status and responsiveness of synapses. Comprehending the mitochondria-related mRNAs regulation and local translation, as well as its influence on mitochondrial morphology near the synapses will help to better understand neuronal physiology and neurological diseases where mitochondrial dysfunction and impaired synaptic plasticity play a central role.

To explore the effect of lily polysaccharide (LP) on immune function and intestinal flora in immunosuppressive mice.The immunosuppressive model was established by intraperitoneal injection of cyclophosphamide (CTX) in mice, and the immunological indexes were measured. The cecal contents of mice were taken, and the DNA of intestinal flora was extracted for 16S DNA sequence analysis.Compared with CTX group, the body weight and thymus index of mice in each treatment group increased significantly, the liver index decreased significantly,the hepatocyte morphology, liver plate and hepatic sinus arrangement of mice in high and low concentration LP groups were relieved in varying degrees, and the contents of IgA and IgG in serum of mice in low concentration LP group and positive control group increased significantly; The contents of TNF-α and IL-6 in colon decreased, while the contents of IL-10 increased significantly. The contents of AST, ALT and MDA in liver decreased significantly, while the content of SOD increased significantly. Compared with the blank group, LP can improve the intestinal flora of immunosuppressive mice , mainly by increasing the abundance of beneficial bacteria such as s24-7, Bacteroides and butyrimionas and reducing the abundance of harmful bacteria such as Prevotella, dorea and adlercreutzia.

المستخلص تصنيع لقاح مكون من الحمض النووي الريبوزي الرسول الخاص بالبروتينات المسئولة عن انتاج البروتينات نيورامنيديز والهيم اجليوتونين لفيروسي الانفلونزا الخنازير والطيورمحاط بجزيئات دهنية بحجم النانوميتر عدوى انفلونزا الخنازير وانفلونزا الطيور مشكلة خطيرة تؤرق العالم كله هذه الايام خصوصا انها مميتة لكثير من اطفال العالم . بعد فترة التعافي من الاصابة تتكون المناعة المكتسبة ضدها لمدة عام تقريبا. هذه الانفلونزا تسبب تسمم فيروسي في الدم بالاضافة للالتهاب الرئوي وهذامن بين اكبرالاسباب للوفاة بين الاطفال قبل سن عامين عالميا بشكل مباشر. الهدف من الدراسة هو انتاج لقاح الحمض النووي الريبوزي الرسول من نوع الام بالنانوتكنولوجي لبروتينات الهيم اجليوتونين والنيورامنيديز الموجودة على سطح هذه الفيروسات التي تساعدتها في الاتصاق بالعائل الذي ستتكاثر داخل خلاياه بالجهاز التنفسي. هذه الدراسة دراسة استكشافية ومن خلالها استطاعنا تصميم هذا اللقاح باستعمال نظام توصيل للقاح بالنانوتكنولوجي حجم جزيئاته 70نانوميمتر. اللقاح الجديد اظهر فاعلية بنسبة 60% واظهر فاعلية حيوية مقاربة واثار جانبية اقل بالمقارنة باللقاحات المتوفرة حاليا بالسوق الدوائي ضد هذا النوع من الفيروسات الوبائية. ABSTRACT Background: Worldwide, Swine and Avian influenza, or the H1N1 and H5N1 serotypes of the Influenza A virus, is a highly contagious illness. In recent years, the global incidence of mortality rate has surpassed 284,000 fatalities. Aim of the study: The production of mRNA vaccine lipid nanoparticles (LNP) to combat the deadly strains of Avian and Swine influenza (H1N1 and H5N1 of the influenza A serotype). Methodology: Polymerase chain reaction (PCR) was used to clone genes of interest encoding Haemagglutinin (HA) and Neuraminidase (NA) of Influenza A virus strains (H5N1 and H1N1) known as Avian flu and Swine flu, respectively. The genes were then inserted using the EcoR1, BAM Hind II restriction endonuclease type II, and Ligase enzyme into the pET-21(+) transcription vector plasmid. On the other hand, the hybrid transcription vectors were mixed with T7 RNA polymerase and ribonucleotides within a test tube after being linearized using EcoR II. Following their purification via reversed-phase high-performance liquid chromatography (RP-HPLC), the mRNAs of the HA and NA were encased in 70 nm LNPs and subjected to reverse-phase high-performance liquid chromatography (RP-HPLC). Lastly, immunogenicity studies were performed in stages 1/2 of randomized human and preclinical clinical trials. Results: The bivalent vaccination had around 63% efficacy in preclinical studies and approximately 60% efficacy in randomized human clinical trials. As shown by the ELISA test, strong neutralizing antibodies against HA were prevalent. Conclusion: The current study is a promising effort because of the development of the novel LNP-mRNA vaccine, which could lower the incidence of Avian and Swine flu infectious disorders.

Background: RSV, or respiratory syncytial virus, is a deadly condition that is present all over the world today. The infection is initially contained in the lower respiratory tract without systemic transmission. The objective of the study: Bioinformatics was used in Egypt to create an mRNA vaccine against the Respiratory syncytial virus (RSV). Methodology: In the present screening experimental study, a lipid nanoparticles vaccine of mRNA of the surface fusion protein of Respiratory syncytial virus was manufactured. The present vaccine delivery system was lipid nanoparticles with a particle size of approximately 90 nanometres, manufactured by the hot micro-emulsion method. In stages 1 and 2 of clinical trials, the immunogenicity of the current mRNA RSV vaccine was evaluated. Results: The current vaccine demonstrated 81% immunogenicity in animal testing, but only 69% in stages 1 and 2 of clinical trials. Its side effects were manageable. The results persisted for a while. In the current trial, the vaccination proved effective as a preventative measure against RSV infection. The current vaccination lacked antibody-dependent enhancement, which causes non-protective antibodies to develop. These non-neutralizing antibodies exacerbate infection by activating cytokines and complement cascade through the formation of immune complexes or enhancement of the virus entry and replication in the host cells. On the other hand, the current RSV mRNA vaccine of the surface fusion protein consequent on the production of powerful neutralizing antibodies with prolonged immunity especially to infants and elderly candidates who received the optimal dosage regimen.

Among the number of hurdles that the vaccines based in modRNA platforms have been facing, there is now another critical one: immune imprinting which decreases even more the effectiveness of the modRNA Covid vaccines.

Background: Interleukins play dual roles in breast cancer, acting as both promoters and 11 inhibitors of tumorigenesis within the tumor microenvironment, which is shaped by their 12 inflammatory functions. This study analyzed the subtype-specific prognostic significance 13 of anti-inflammatory and pro-inflammatory signatures using microarray-based gene ex- 14 pression analysis. Correlations between these interleukin signatures and immune cell 15 markers (CD8, IgKC, CD20) and immune checkpoints (PD-1) were also evaluated. 16 Materials and Methods: The study investigated the prognostic significance of an anti- 17 inflammatory interleukin signature (IL-12, IL-21, IFN-γ) and a pro-inflammatory interleu- 18 kin signature (IL-4, IL-5, IL-10, IL-13, IL-17, CXCL1) for metastasis-free survival (MFS) 19 using Kaplan-Meier curves and Cox regression analyses in a cohort of 461 patients with 20 early breast cancer. Correlations were analyzed using the Spearman-Rho correlation coef- 21 ficient. 22 Results: Kaplan-Meier curves revealed that the prognostic significance of the anti-inflam- 23 matory signature was specifically pronounced in the basal-like subtype (p=0.004, Log 24 Rank). This signature retained independent prognostic significance in multivariate Cox 25 regression analysis (HR 0.463, 95% CI 0.290-0.741; p=0.001). Higher expression of the anti- 26 inflammatory interleukin signature was associated with longer MFS. The pro-inflamma- 27 tory interleukin signature showed a significant prognostic effect in the whole cohort, with 28 higher expression associated with shorter MFS (p=0.034). Strong correlations were found 29 between the anti-inflammatory signature and CD8 expression (ρ=0.391; p<0.001) and be- 30 tween the pro-inflammatory signature and PD-1 expression (ρ=0.627; p<0.001).

Background: The study was conducted to investigate if the mRNA vaccine technology could be adapted for the ectothermic vertebrate Atlantic salmon (Salmo salar). The lipid nanoparticle (LNP) technology has been developed and optimized for mRNA vaccines in mammals, stabilizing mRNA and facilitating delivery into cells. However, its utility at the temperature and specific biological environment in ectotherms remains unclear. In addition, it is unknown if modified mRNA containing non-canonical nucleotides can correctly translate in salmonid cells. Methods: We used an mRNA transcript coding for enhanced green fluorescence protein, flanked by the untranslated regions of the hemagglutinin-esterase gene of infectious salmon anemia virus, and a 120-base-long poly(A) tail. The mRNA was generated by in vitro transcription where uridine residues were replaced with N1-methyl-pseudouridines, and then encapsulated in LNPs. Results: When transfected into the salmonid cell line CHH-1, the mRNA-LNP construct induced expression of EGFP. Furthermore, when mRNA-LNPs were injected intramuscularly into salmon, in vivo protein expression was demonstrated by immunohistochemistry. EGFP was observed in cells infiltrating the space between the muscle cells in a focal inflammatory response. Conclusion: The results indicate that the N1-methyl-pseudouridine modified mRNA encapsulated in LNPs can be used to express antigens of interest in salmonid fish.

mRNA-lipid nanoparticle (LNP) medicinal products can be considered a platform technology because the development process is similar for different diseases and conditions, with similar noncoding mRNA sequences and lipid nanoparticles and essentially unchanged manufacturing and analytical methods utilised often for different products. It is critical not to lose the momentum built using the platform approach during the development, regulatory approval and rollout of vaccines for SARS-CoV-2 and its variants. This Review proposes a set of modifications to existing regulatory requirements for mRNA products, based on a platform perspective for quality, manufacturing, preclinical and clinical data. For the first time, we address development and potential regulatory requirements when the mRNA sequences and LNP composition vary in different products as well. In addition, we propose considerations for self-amplifying mRNA, individualised oncology mRNA products and mRNA therapeutics. Providing a predictable development pathway for academic and commercial groups, so they can know in detail what product characterisation and data are required to develop a dossier for regulatory submission, has many potential benefits. These include reduced development and regulatory costs; faster consumer/patient access and more agile development of products in the face of pandemics; and for rare diseases where alternatives may not exist or to increase survival and the quality of life in cancer patients. Therefore, achieving consensus around platform approaches is both urgent and important. This approach with mRNA can be a template for similar platform frameworks for other therapeutics and vaccines to enable more efficient development and regulatory review.

The aims of the study are: a) Describe the reactogenicity of WHO-approved two mRNA (Pfizer-BioNTech, Moderna) and two non-RNA vaccines (Oxford-AstraZeneca, Sinovac) among lactating mother and baby pairs; and b) compare and contrast the reactogenicity between mRNA and non-mRNA vaccines. A cross-sectional, self-reported survey was conducted amongst 1784 lactating women who received COVID-19 vaccinations. The most common maternal adverse reaction was a local reaction at the injection site; the largest minority of respondents, 43.7% (780/1784), reported experiencing worse symptoms when receiving the second dose compared to the first dose. There were no major reported adverse effects or behavioural changes in the breastfed infants. Among the respondents who received non-mRNA COVID-19 vaccinations, a majority reported no change in lactation but those who did more commonly reported an increase in milk supply, decrease in milk supply and pain in the breast. The more commonly reported lactation changes (fluctuations in breastmilk supply and pain in the breast) for the non-mRNA vaccines were similar to that of respondents who received mRNA vaccines. Our study, with a large cohort and wide geographical and racial mix, further augments earlier reported findings that COVID-19 vaccines are safe for breastfeeding mothers and her children.

Background: Respiratory syncytial virus[ RSV] is a lethal overwhelming defectiveness that influences people all over the world. The infection gets down in the lower respiratory tract and does not disperse to the remainder of the body. The objective of the study: Bioinformatics was used to create an mRNA vaccine against the Respiratory syncytial virus( RSV). Methodology: Lipid nanoparticle vaccines containing the Respiratory syncytial virus's surface fusion protein's mRNA were created for the current screening experimental investigation. Lipid nanoparticles[ LNP] with a particle size of around 90 nanometres that were created using the hot micro-emulsion process comprise the current vaccine delivery system. In stages 1 and 2 of clinical trials, the immunogenicity of the current mRNA RSV vaccine was evaluated. Results: The current vaccine demonstrated 81% immunogenicity in animal testing, but only 69% in stages 1 and 2 of clinical trials. Its side effects were manageable. The results persisted for a while. In the current trial, the vaccination proved effective as a preventative measure against RSV infection. The current immunization lacks antibody-dependent enhancement, which causes non-protective antibodies to develop. These non-neutralizing antibodies worsen infection by enhancing viral entrance and replication in the host cells, activating cytokines and the complement cascade through the production of immunological complexes, or both. However, the current LPN-RSV mRNA vaccine of the surface fusion protein resulted in the formation of potent neutralizing antibodies with persistent protection, especially for newborns and elderly individuals who get the ideal dose regimen. Conclusion: The invention of the LNP-mRNA RSV vaccine, which might prevent RSV-caused bronchiolitis and fatal pneumonia, made the current study promising

This review highlights the potential and limitations of mRNA vaccines with a particular focus on mucosal delivery as an alternative to parenteral administration. The strengths of mRNA vaccines are: a) Versatility: they can be adapted to target a wide range of pathogens; b) Faster development: designed and produced more quickly than traditional vaccines; c) High efficacy: effective in preventing severe disease, as demonstrated during the COVID-19 pandemic. Current challenges: a) Delivery: current methods (mainly intramuscular injection) may not be optimal for inducing mucosal immunity; b) Stability: mRNA is fragile and needs to be protected from degradation; c) Safety: potential side effects, including myocarditis, blood clotting, allergic reactions need further investigation. Mucosal delivery could be more effective in preventing the transmission of pathogens and is generally better accepted by the population. Pros: offers the potential to induce local immunity at the site of pathogen entry, potentially providing broader protection; Cons: developing effective delivery systems and adjuvants for mucosal delivery is difficult. Extracellular vesicles as a mucosal delivery system are promising and offer a potentially safe, scalable, and needle-free approach. Future directions: a) Optimizing mRNA constructs: strategies like codon optimization and self-amplifying RNA can improve stability and translation efficiency; b) Rigorous pre-clinical studies are essential before human trials.

Improvement of hydrophysical properties and corrosion resistance of self-compacting concrete to the effects of alternate freezing-thawing and aggressive soils of southern and central Kazakhstan is of interest to a wide range of researchers from the side of practical application of the obtained results in construction practice. It is proposed to form a spatially reinforced fine crystalline structure of cement matrix with maximum dense packing by using a complex modifier (Hyperplasticiser + Polymer + Microsilica + Fibro fibers) in the composition of self-compacting concretes (SCC). The introduction of the calculated amount of the above additives increases the operational reliability of the current SCC compositions, increasing the water resistance to W16, frost resistance to F=500, increasing the compressive strength by 20%, reducing the mass loss of samples during corrosion leaching to 50%. It has been experimentally established that the proposed addition of complex modifier (Hyperplasticiser + Polymer + Microsilica + Fiber fibers) to the SCC composition allows obtaining self-compacting concrete of high quality with improved performance characteristics (compressive strength, water resistance, frost resistance and corrosion resistance). Studies have shown that the complex modifier-modified SCC compositions have a high degree of resistance in aggressive environments and leaching corrosion. Based on the results of the conducted tests, it is possible to recommend the obtained SCC compositions for production of building products working in the zone of alternating freezing-thawing and aggressive soils.

Recently, Mulroney,et.al., demonstrated that Pfizer’s ModRNA Covid vaccine, but not AstraZeneca Covid vaccine, produce aberrant foreign proteins in vivo due to reading frame shift in ribosomes. This phenomenon could elucidate the notable surge in autoimmune diseases following the administration of ModRNA vaccines compared to Influenza vaccines between 2020 and 2023, as found in the VAERS database. These findings bear significant implications for the future application of mRNA technology, emphasizing the necessity of modifying the design of the mRNA sequence to mitigate these defects. Remarkably, Mulroney and collaborators achieved a reduction in frame shift proteins by introducing additional edits to the mRNA sequences. This adjustment is pivotal for rectifying the flawed design of the ModRNA employed by Pfizer. In light of these findings, many advocate for the immediate recall and further investigation of these products. The notion of a "future mRNA-based therapy" should be postponed indefinitely.

A recent study revealed a persistent presence of the PP-Spike recombinant protein in 50% of individuals who received ModRNA injections, contrasting with unvaccinated controls, whether SARSCoV-2 infected or not, up to 187 days post-injection. The implications of these findings are discussed in the context of PP-Spike recombinant protein-induced hyperimmune/inflammatory reactions and thrombotic vasculitis as mechanisms to elucidate the serious side effects, long-term organ complications, and excess deaths observed after administering Covid ModRNA products. These results underscore the urgent need for a comprehensive reassessment of the risk-benefit profile of ModRNA injections, including an immediate halt in their use for any person, and a renewed emphasis on understanding and addressing their long-term effects on human health

In the present work report, the MgAl₂O₄and the Ag/MgAl₂O₄ samples were successfully synthesized by the modified hydrothermal and the isovolumetric impregnation methods, respectively. The structural properties of the prepared samples were systematically characterized by XRD, SEM, TEM, DRS, XPS and et al techniques. The photocatalytic degradation of methylene blue by the Ag/MgAl₂O₄ and MgAl₂O₄ samples was comparatively studied under UV lamp irradiation. The results revealed that the prepared Ag/MgAl₂O₄ (pH=6) samples were the most active among the samples in photocatalytic of methylene blue. Under UV lamp irradiation, the Ag/MgAl₂O₄ (pH=6) photodegradation of methylene blue reached to 89.6% within 120 min. And the Ag/MgAl₂O₄ (pH=6) complex photocatalysts displayed a high photochemical stability under repeated irradiation. Repeated irradiate the Ag/MgAl₂O₄ (pH=6) compound, which indicated it had a high photochemical stability.

In this study we have investigated the effect of the addition of Nb2O5 (up to 5 mol%) on the structure and luminescent properties of ZnO-B2O3 glass doped with 0.5 mol % Eu2O3 by using of infrared (IR), Raman and photoluminescence (PL) spectroscopy. Physical properties as molar volume, oxygen packing density and glass transition temperature were determined using the results of differential thermal analyisis (DTA) and Archimedes principle for density. IR and Raman spectra revealed that niobium ions incorporate into the base zinc borate glass as NbO4 trtraherda and NbO6 octahedra. A strong red emission from the 5D0 level of Eu3+ ions was registered under near UV (392 nm) excitation using the sharp 7F0 - 5L6 transition of Eu3+. The integrated fluorescence intensity ratio R (5D0 → 7F2/5D0 → 7F1) was calculated to estimate the degree of asymmetry around the active ion, suggesting a location of Eu3+ in non-centrosymmetric sites. The higher Еu3+ luminescence emission observed in zinc borate glasses containing 1÷5 mol% Nb2O5 compared to the Nb2O5-free zinc borate glass evidences that Nb2O5 is suitable component for modification of host glass structure and improving the emission intensity.

Plants significantly shape root-associated microbiota, making rhizosphere microbes useful environmental indicator organisms for safety assessment. Here, we report the pyrosequencing of the bacterial 16S ribosomal RNA in rhizosphere soil samples collected from transgenic cry1Ab/cry1Ac Bt rice Huahui No. 1 (GM crop) and its parental counterpart, Minghui63. We identified a total of 2,579 quantifiable bacterial operational taxonomic units (OTUs). Many treatment-enriched microbial OTUs were identified, including 14 NonGM-enriched OTUs and 10 GM-enriched OTUs. The rhizosphere microbiota communities were influenced more strongly by growth in the field than by rice varieties. Furthermore, Huahui No. 1 transgenic Bt rice had a greater impact on the rhizosphere bacterial communities than Minghui63. Early developmental stages of the transgenic Bt rice had a significant impact on many Bacillaceae communities. While soil chemical properties were not significantly altered by the presence of transgenic Bt rice, we found peak expression level of Bt proteins during the seedling stage, which may be an intriguing factor for bacterial diversity variations. Based on these findings, we conclude that transgenic Bt rice has a significant impact on root-associated bacteria. This information may be leveraged in future environmental safety assessments of transgenic Bt rice varieties.

High dimensional datasets are highly likely to have redundant, irrelevant, and noisy features that negatively affect the performance of the classification algorithms. Selecting the most relevant features and reducing the dimensions of datasets by removing the undesired features is a dimensional reduction technique called Feature Selection (FS). In this paper, we propose an FS approach based on the Black Hole Algorithms (BHO) with a mutation technique called MBHO. Generally, BHO contains two major phases. At the exploitation phase, a set of stars are modified based on some rule and according to some objective function, the best star is selected as the black hole which attracts other stars. Furthermore, when a star gets closer to the event horizon, it will be swallowed and a new one will be randomly generated in the search space which thus is the exploration phase. However, randomness may cause the algorithm to fall into the trap of local optima, and to overcome such complications, inversion mutation is used. Furthermore, we modify a widely utilized objective function in most of the proposed works for wrapper feature selection by combining two new terms that are based on the correlation among the selected subset of features and the features and the classification label. We also utilize a transfer function, known as the V2 transfer function, to convert continuous values into discrete ones to enhance search. We assess our approach via extensive evaluation experiments using fourteen benchmark datasets. We benchmark the performance of a wrapper FS approach called Binary Cuckoo Search (BCS), and three filter-based FS approaches (namely Mutual Information Maximisation (MIM), Joint Mutual Information (JMI), and minimum Redundancy Maximum Relevance (mRMR)). Our evaluation has shown that the proposed model is an effective approach for FS, in selecting better features that enhance the performance metrics on the classifiers. Thus, MBHO can be utilized as one alternative to the existing state-of-art-approaches. We release the source codes of our implementation for the community to build on with new methods and datasets.

Fire detection is crucial for ensuring human safety and minimizing property damage. By utilizing advanced technologies, we can identify fires early, before they escalate. Autonomous fire detection systems are particularly vital in high-risk areas with minimal human presence. To address this need, we propose an automated fire-detection model based on YOLOv8. We modified the architecture of YOLOv8 and achieved impressive performances. Through comprehensive analysis of different YOLO models and their predecessors, we identified and addressed substantial gaps in this field. Also, by augmenting the framework with additional capabilities, we surpassed previous models, enabling real-time fire detection. Our proposed model achieves impressive performances, with 98% accuracy in fire detection and 97.8% in smoke detection. Moreover, recall rates for fire and smoke are 97.1% and 97.4%, respectively, with a mean average precision (mAP) accuracy of 99.1% for both cases. Finally, we applied an explainable artificial intelligence technique to interpret our proposed model and its results. This study lays the foundation for future research aimed at enhancing fire detection efficiency. The reliability of our modified model presents promising opportunities for future advancements, ensuring increased effectiveness and precision in efficient fire detection.

This study examines stress distributions in adhesive joints under various loading and temperature conditions. Finite element analysis (FEA) was employed to compute the peel and shear stresses at the adhesive interface and bondline mid-section. Dependency analysis shows that mid-section peel stress significantly impacts the experimental shear strength of SLJs more than shear stress. This insight highlights the need to carefully analyze peel stress and bending moment factors. The analytical solutions proposed by Goland and Reissner were analyzed with modifications by Hart-Smith and Zhao. Hart-Smith’s approach performed more effectively, especially when the adhesive layer thickness (t_a) is 0.5 mm and the overlap length to thickness ratio (c/t_a) is ≥20. FEA revealed stress distributions at the adhesive/adherend interface and bondline mid-section. DP490 adhesive joints exhibited lower stresses than EA9696. Temperature variations significantly affected joint behavior, particularly above the adhesive’s glass transition temperature (T_g). Both EA9696 and DP490 adhesive joints displayed distinct responses to stress and temperature changes. The parabolic and biquadratic solutions for functionally graded adhesive (FGA) joints were compared. The biquadratic solution consistently yielded higher shear and peel stress values, with an increase ranging from 15% to 71% compared to the parabolic solution at various temperatures because of larger gradient of the Young's modulus distribution near the overlap ends. The ratio of peak peel stress to peak shear stress suggests selecting an adhesive with a superior peel strength or primarily reducing the peak peel stress by functionally grading is advisable, particularly if the adhesive is brittle. Comparison of stress distributions emphasize the importance of selecting adhesives based on stress type, temperature, and solution methods in optimizing adhesive bonding applications. These findings provide valuable insights for thermomechanical applications where thermal stimuli may be used for controlled debonding.

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

A novel approach to optimizing turbomachinery performance is presented in this chapter, which integrates Computational Fluid Dynamics (CFD) simulations, an artificial neural network (ANN) with a modified Non-dominated Sorting Genetic Algorithm II (NSGA-II). Using this enhanced algorithm, substantial performance improvements can be achieved through geometric optimization. The effectiveness of this method is demonstrated in two case studies: an inducer for a centrifugal pump and a Savonius wind turbine. The inducer is designed to maximize head coefficient, hydraulic efficiency, and net positive suction head by optimizing factors such as inlet and outlet blade angles. The optimization process employs the Group Method of Data Handling (GMDH) for objective function modeling, followed by Pareto front plotting and TOPSIS for identifying trade-off optimal points. Results indicate significant improvements in head coefficient, hydraulic efficiency, and NPSHR by 14.3%, 0.3%, and 30.2%, respectively. Twist angle, aspect ratio, and overlap ratio are also optimized for wind turbine blades. The power coefficient is enhanced by 5.32%, the torque coefficient by 13.74%, and the rotational speed by 0.071% through multi-objective optimization. As a result of this approach, efficiency improves, and valuable insights into the optimal design principles for turbomachinery components are also gained.

Cementitious materials exhibit excellent binding properties and micropore structures that support the stabilization of TiO2 nanoparticles within the matrix. Therefore, these materials are ideal for the development of functional construction products with TiO2 nanoparticles. This study investigated the degree of hydration, microstructure, and mechanical properties of cement-containing TiO2 nanoparticles. The experimental results demonstrated that TiO2 nanoparticles accelerated the hydration rate of cement, reducing the setting times. Moreover, TiO2 nanoparticles changed matrix microstructure, decreasing the porosity and improving early-age strength. Although TiO2 nanoparticles function as nucleation sites in the cement hydration reaction, the tendency of the particles to clump implies that proper dispersion should be ensured when mixing in large quantities. When developing new building materials incorporating TiO2 nanoparticles, considering the effect of TiO2 nanoparticles on the hydration reaction of cementitious materials is crucial.

Traditional vaccines are produced by using weakened or inactivated forms of disease-causing pathogens to produce the target antigen they are designed to protect against. Messenger RNA vaccines are a class of vaccines that employ a minute segment of genetic material, known as messenger RNA (mRNA), which contains directives for the cells in the body to generate a particular protein. This genetic material is synthesized in the laboratory and packaged into a lipid nanoparticle, which protects and helps it enter cells for further protein synthesis. During vaccination with mRNA vaccine, the lipid nanoparticles containing the mRNA are injected into the muscle of vaccinees. Once inside the cells, the mRNA instructs the cells to produce a protein which is then displayed on the surface of the cell, triggering an immune response. During this, the immune system recognizes the displayed protein as foreign and mounts a defense by producing antibodies and activating immune cells to target and eliminate the protein. Furthermore, these immune responses generate a memory cell, facilitating the immune system to promptly react in case of encountering the authentic pathogen as an infection in the future. The mRNA vaccines are flexible and the sequence can be easily synthesized in the lab based on the genetic information of the target pathogen. Additionally, mRNA vaccines can be developed for new strains or variants of the target disease easily. This was particularly evident during the COVID-19 pandemic, where mRNA vaccines like the Pfizer-BioNTech and Moderna vaccines were developed and authorized for emergency use within a year. But currently, available mRNA vaccines require extensive cold chain, antigen delivery, potential immune response variability optimization, and sophisticated manufacturing process. The efforts to explore next-generation mRNA vaccine development are aimed to further improve the effectiveness, stability, and delivery methods. One focus of research has been to enhance the stability of mRNA vaccines, particularly temperature sensitivity which makes storage and distribution easier, particularly in regions with limited access to cold chain infrastructure. Self-amplifying mRNA vaccines, on the other hand, are designed to generate multiple copies of the mRNA within cells which potentially leads to a higher production of the target protein, resulting in a stronger immune response. Additionally, studies are exploring new delivery systems to improve the target and efficiency of mRNA vaccines using specialized nanoparticles and liposomes to specifically deliver mRNA to certain cell types or immune cells. Another area of interest is the development of combination vaccines, where multiple mRNA sequences are included in a single vaccine protecting against multiple diseases targeting strains or variants of a particular pathogen simultaneously. While current mRNA vaccines are administered via intramuscular injection, studies are underway to deliver directly into the skin offering enhanced immune response and the ability to use smaller vaccine doses.

: The activated carbons (ACs) derived from okara powder waste with high surface areas were modified with ammonia aqueous solution impregnation in an autoclave to enhance their CO2 adsorption properties toward CO2. The impregnated ACs were characterized in which surface chemical composition and properties of the ACs were analyzed by SEM-EDX, FTIR. Activated carbons were functionalized with ammonia aqueous solution (25%) through a hydrothermal process within 24; 48, and 72 hours. The adsorption performance of CO2 onto carbon samples was experimentally evaluated through a TPD CO2 measurement. FTIR spectra confirm the N-containing in N-modified activated carbons and the presence of the –C = O stretch and N-H groups. CO2 uptakes of N-modified activated carbons are 0.24; 1.78; 2.24 and 1.26 mmol/g, which are relatively comparable with those of activated carbons studied in in the literature.

In order to enhance the efficiency and combined performances of nitriding layer, aluminum-modified plasma nitriding (Al-PN) was developed in this research by adding some FeAl particles around the samples during plasma nitriding (PN) for 42CrMo steel. The results show that the efficiency is dramatically enhanced almost 6 times comparing with traditional PN, with the effective hardening layer increasing from 224 μm to 1246 μm at 520℃/4h. More importantly, the compound layer increased just a little bit from 11.64 μm to 14.32 μm, which remarkably reduces the ratio of the compound layer thickness to effective hardening layer thickness, thus being quite beneficial to decrease the brittleness level, making the brittleness level decreasing from Level 4 to Level 1. Meanwhile, ultra-high surface hardness and excellent wear behaviors are obtained by aluminum-modified plasma nitriding (Al-PN) due to the formation of dispersed strengthening phased of AlN and FexAl in the nitriding layer, with the surface hardness increasing from 755 HV0.025 to 1251 HV0.025, wear rate decreasing from 8.15 x10-5g N-1 m-1 to 4.07 x10-5g N-1 m-1. In other words, comparing with PN, the wear resistance has been almost doubled by Al-PN. Therefore, the research can provide comprehensive insights into the surface characteristics and combined performances of the aluminum-modified plasma nitriding layer.

The activated carbons (ACs) derived from okara powder waste with high surface areas were modified with ammonia aqueous solution impregnation in an autoclave to enhance their CO2 adsorption properties toward CO2. The impregnated ACs were characterized in which surface chemical composition and properties of the ACs were analyzed by SEM-EDS, FTIR. Activated carbons were functionalized with ammonia aqueous solution (25%) through a hydrothermal process within 24; 48, and 72 hours. The adsorption performance of CO2 onto carbon samples was experimentally evaluated through a breakthrough adsorption experimental setup at room temperature. FTIR spectra confirm the N-containing in N-modified activated carbons and the presence of the –C = O stretch and N-H groups. CO2 uptakes of N-modified activated carbons are 0.24; 1.47; and 1.20 mmol/g, which are relatively comparable with those of activated carbons studied in in the literature.

The article presents the results of research work devoted to the study of composite materials on polymer binder with the content of modified mineral filler - water-dispersion paint and varnish materials on acrylic polymer with modified filler - diatomite. The aim of the study is to obtain polymer-based composites with modified diatomite (water-dispersion paint on acrylic binder) with improved performance properties. Methods: determination of porosity, adhesion, elasticity, hiding power of the control composition; determination of porosity, adhesion, elasticity, hiding power of the obtained composites with the use of modified filler; investigation of the influence of radiation in the infrared radiation (IR) region of the spectrum of the paint coating surface using FLIRB620 thermal imager. As a result of work it is noticed that modification of water dispersions by silica activated diatomite promotes elimination of the main disadvantages of materials and coatings on the basis of acrylate binder - low water resistance and low physical and mechanical characteristics, introduction of modified diatomite into water emulsion paint on acrylate basis does not lead to deterioration of the main operational characteristics of paint and varnish coatings - porosity, adhesion, elasticity and covering. When analyzing the effect of emissivity in the IR region of the spectrum of the paint coating surface, a significant effect of the quantitative content of modified diatomite on the reduction of emissivity of paint coatings in the IR region of the spectrum was established and it was shown that a significant effect of the reduction of emissivity of paint coatings in the IR region of the spectrum is provided by the introduction of modified diatomite in the amount of 40 wt.h. into the mixture. The influence of the time of full-scale tests in the investigated small range regardless of the quantitative composition of modified diatomite on the performance characteristics of the paintwork was established.

At present there is a renewed interest in theories of ”modified” gravity. Here, under a more drastic modification enforced by Galilei group, we obtain a completely new gravitational structure, and which exists in addition to the already available general relativity of today. Correlated with this, we show that in addition, there is a new ”modified” quantum mechanics, in as much as it exists as an independent and new ”pure” non-relativistic quantum me- chanics, and which has no relativistic counterpart. This is in addition to the present quantum mechanics, where the relativistic and non-relativistic structures are counterparts of each other. The above holds, firstly due to the correlation between Galilei group and quantum mechanics. These math- ematical conclusions are consolidated by the fact that there exists a physical Majorana interaction between each neutron- proton pairs in nuclei. Galilei invariance of Majorana exchange in Majorana interaction, shows that the mass here is of pure gravitational nature, and which is immune to the other three forces. This makes an amazing connection between the gravitational force and the quantum mechanics. This pure gravitational mass would man- ifest itself as dark matter of the universe. It is our new modified gravity that generates the dark matter.

Semenov-Tian-Shansky has introduced the modified classical Yang-Baxter equation, which is called the modified $r$-matrix. Relevant studies have been extensive in recent times. This paper is devoted to study cohomology theory of modified Rota-Baxter pre-Lie algebras and its applications. First we introduce the concept and representations of modified Rota-Baxter pre-Lie algebras. We then develop the cohomology of modified Rota-Baxter pre-Lie algebras with coefficients in a suitable representation. As applications, we consider the infinitesimal deformations, abelian extensions and skeletal modified Rota-Baxter pre-Lie 2-algebra in terms of lower degree cohomology groups.

Human Immunodeficiency Virus (HIV) infection and its latent recurrent infection make vaccine development a significant challenge for traditional vaccines; however, the mRNA delivery of multiepitope antigens capable of creating antibodies against the surface proteins of HIV-1 and HIV-2 along with their respective Nef proteins, responsible for the latent infection can bring a most effective, as well as affordable solution to the unresolved epidemics of HIV. In this paper, we present the complete design of a multiepitope vaccine to prevent acute infections and inactivate Nef proteins that block the MHC-1 and MHC-2 pathways to hide the virus for later reinfection.

Infection with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which has reached pandemic proportions. A number of effective vaccines have been produced, including mRNA vaccines and viral vector vaccines, which are now being implemented on a large scale in order to control the pandemic. The mRNA vaccines are composed of the Spike S1 protein encoding mRNA, incorporated in a lipid nanoparticle, stabilized by polyethylene glycol (PEG). mRNA vaccines are novel in many respects, including cellular uptake, the intracellular routing, processing, and secretion of the viral protein. Viral vector vaccines have incorporated DNA sequences encoding the SARS-CoV-2 Spike S1 protein into (attenuated) adenoviruses. The antigen presentation routes in MHC class I and class II, in relation to induction of virus neutralizing antibodies and cytotoxic T-lymphocytes will be reviewed. In rare cases, mRNA vaccines induce unwanted immune mediated side effects. mRNA based vaccines may lead to an anaphylactic reaction. This reaction may be triggered by PEG. The intracellular routing of PEG, and potential presentation in the context of CD1 will be discussed. Adenovirus vector based vaccines have been associated with thrombocytopenic thrombosis events. The anti-platelet factor 4 antibodies found in these patients could be generated due to conformational changes of relevant epitopes presented to the immune system.

The article presents the results of research work devoted to improving the characteristics of paint and varnish coatings based on aqueous dispersions of polyacrylates, it is proposed to modify them by introducing mineral raw materials as fillers and hydrated lime with subsequent processing in a vortex layer apparatus. Introduction of activated diatomite does not cause deterioration of covering power, adhesion and increase of porosity of the paint material. Modification of coatings contributes to the increase of their operational properties, which can be associated with the reduction of free volume in the composite, formation of polymer boundary layers with modified physical and chemical properties. The aim of the study is to obtain water-dispersion paint and varnish composition containing modified diatomite on polyacrylate basis and subsequent study of the main physical and mechanical parameters. The work has been carried out by the following method: determination of porosity, adhesion, elasticity, covering power of the control composition; determination of porosity, adhesion, elasticity, and covering power of the obtained composites using modified filler; investigation of the influence of radiation in the infrared spectrum of the paint coating surface using FLIRB620 thermal imager. As a result of research works it was noticed that modification of water dispersions with silica activated diatomite helps to eliminate the main disadvantages of materials and coatings based on acrylate binder - low water resistance and low physical and mechanical characteristics, introduction of modified diatomite into water emulsion paint on acrylate base does not lead to deterioration of the main performance characteristics of paint coatings - porosity, adhesion, elasticity and covering.

Local food has continued to become more popular in both the home and as featured ingredients in all segments of food service. Numerous studies have explored the motivating factors for consumer purchasing motivators. However, no known study has explored if there is a correlation between ego and intent to buy local foods. This study adopted a modified version of the Theory of Trying and surveyed a sample of 237 food service buying agents in South Carolina to examine their perceptions of buying local. Results suggest that ego is a predictor of trying to purchase local foods for restaurants. It was also found that the modified model is an acceptable model for predicting buyer intent. These findings support the majority of the studies looking at ego-centric behaviors with green purchases and could potentially help local food suppliers to better market their products to foodservice establishments. This study could also act as the foundation for future studies to explore the full extent of ego’s motivational effect on purchasing intentions in the food service industry.

Three kinds of inorganic alkali are introduced into tetraethylenepentamine (TPEA) and polyethyleneimine (PEI) modified MCM-41 as the CO2 adsorbents. FT-IR and TGA are used to characterize the surface groups and the thermal stability of adsorbents. Chemical titration method is used to measure the alkali amounts of adsorbents. Thermo-gravimetric analysis with 10%CO2/N2 as the simulated flue gas is used to test the CO2 adsorption performance of adsorbents. The results show that all three kinds of inorganic alkali containing adsorbents exhibit promoted CO2 adsorption capability than traditional TPEA and PEI modified samples. Ca(OH)2 and PEI modified samples exhibit the highest adsorption capacity and stable regeneration property. The introduction of inorganic alkali changes the chemical adsorption mechanism between CO2 and increases the effective alkali amounts due to its hydroxyl groups. The CO2 adsorption capacities have a linear dependence relation with the alkali amounts of adsorbents, indicating that alkali amount is a critical factor for novel adsorbents exploring.

The B169L protein (pB169L) of African swine fever virus (ASFV) is a structural protein with an unidentified function during the virus replication. The sequences of the B169L gene and the downstream B438L gene are separated by short intergenic regions. However, the regulatory mode of the gene transcription remains unknown. Here, we identified two distinct promoter regions and two transcription start sites (TSS) located upstream of the open reading frame (ORF) of B438L. Using the promoter reporter system, we demonstrated that the cis activity of the ORF proximal promoter exhibited significantly higher levels compared with that of the distal promoter located in the B169L gene. Furthermore, transfection with the plasmids with two different promoters for B438L could initiate the transcription and expression of the B438L gene in HEK293T cells, and the cis activity of the ORF proximal promoter also displayed the higher activities compared with the distal promoter. Interestingly, the B438L distal promoter also initiated the transcription of the alternatively spliced B169L mRNA (B169L mRNA2) encoding a truncated pB169L (tpB169L) (amino acids 92–169), and the gene transcription efficiency was increased upon mutation of the initiation codon located upstream of the alternatively spliced B169L gene. Taken together, we demonstrated that the distal promoter of B438L gene initiates the transcription of both the B438L mRNA and B169L mRNA2. Comprehensive analysis of the transcriptional regulatory mode of the B438L gene is beneficial for the understanding of the association of B438L protein and pB169L and the construction of the gene-deleted ASFV.

In this paper, we identify several relative ordering properties of the modified proportional hazard rate and modified proportional reversed hazard rate models. For this purpose, we use two well-known relative orderings, namely the relative hazard rate ordering and the relative reversed hazard rate ordering. The investigation is to see how a relative ordering between two possible base distributions for the response distributions in these models is preserved when the parameters of the underlying models are changed. We will give some examples to illustrate the results and the conditions under which they are obtained.

Heavy metals are dangerous contaminants constituting a threat to human health because they persist in soils and are easily transferred into the food chain, causing damages to human health. Among heavy metals, nickel appears to be one of the most dangerous responsible for different disorders. Public health protection requires nickel detection in environment and food chains; a simple, rapid and sensitive method to detect nickel contamination is represented by biosensors. In this paper we report the setup of a whole-cell based system, in which protoplasts, obtained from Nicotiana tabacum leaves, were used as transducers to detect the presence of heavy metal ions and, in particular, nickel ions. Protoplasts were genetically modified with a plasmid containing the GFP reporter gene under the promoter region of a sunflower small HSP gene control. By this device the presence of heavy metal ions was detected. Thus, the possibility to use this whole-cell system as a novel tool to detect the presence of nickel ions in food matrices was assessed.

In this paper, a new way to obtain photoactive cements was presented. In this method amorphous TiO2 is added to cooler during the cooling of the cement clinker (Górażdże company) during cement production. Amorphous TiO2 was taken from the installation for obtaining titanium dioxide using the sulphate method. During the studies amorphous TiO2 was added to clinker at different temperature 300, 600, 700 and 800 °C. The properties of the obtained cement were tested during the bending and compressive strength and beginning and the end of bending setting time measurements. The adhesion of the obtained materials to concrete block, ceramic brick and plasterboard were also evaluated. The photocatalytic activity of the obtained materials was studied during NO and BTEX (benzene, toluene, ethylbenzene, p-,m-,o-xylenes decomposition) decomposition. Cement with 5 wt.% TiO2 added to clinker at 700 C had the highest photocatalytic activity and the best mechanical properties.

In this paper, we define the cohomology of a modified $\lambda$-differential left-symmetric algebra with coefficients in a suitable representation. We also introduce the notion of modified $\lambda$-differential left-symmetric 2-algebra. We classify linear deformations and abelian extensions of modified $\lambda$-differential left-symmetric algebras using the second cohomology group and classify skeletal modified $\lambda$-differential left-symmetric 2-algebra using the third cohomology group as our propose cohomology applications. Moreover, we prove that strict modified $\lambda$-differential left-symmetric 2-algebras are equivalent to crossed modules of modified $\lambda$-differential left-symmetric algebras.

This research paper examines a cosmological model in flat space-time via $f(R,G)$ gravity where $R$ and $G$ are respectively the Ricci scalar and Gauss-Bonnet invariant. Our model assumes that $f(R,G)$ is an exponential function of $G$ combined with a linear combination of $R$. We scrutinize the observational limitations under a power law cosmology that relies on two parameters - $H_0$, the Hubble constant, and $q$, the deceleration parameter, utilizing the 57-point $H(z)$ data, 8-point BAO data, 1048-point Pantheon data, joint data of $H(z)$ + Pantheon, and joint data of $H(z)$ + BAO + Pantheon. The outcomes for $H_0$ and $q$ are realistic within observational ranges. We have also addressed Energy Conditions, $Om(z)$ analysis and cosmographical parameters like Jerk, Lerk and Snap. Our estimate of $H_0$ is remarkably consistent with various recent Planck Collaboration studies that utilize the $\Lambda$CDM model. According to our study, the power law cosmology within the context of $f(R,G)$ gravity provides the most comprehensive explanation for the important aspects of cosmic evolution.

Polyphenols are the most common organic compounds in wine. They improve both the sensory aspects of wine and human health by activating antioxidant systems. Therefore, there is a great need for a simple, fast and accessible method to determine the polyphenol content of wine. The aim of this study is to characterize polyphenolic compounds in natural wine samples using an electrochemical method and a modified carbon paste electrode with TiO2 nanoparticles. This work is motivated by the promising improvement of the sensing properties of a TiO2 nanoparticle-modified carbon paste electrode observed in the electrooxidation of different polyphenols. Since the voltammetric response of wine is largely irreversible, another motivation was the possibility of improving the processing of voltammograms to obtain data indicative of wine polyphenols, based on the approach described in the seminal work by Espinoza et al. The modified electrode studied provides an improved and reproducible voltammetric response of gallic acid in wine samples and provides a good basis for further development of an integrated sensor/data system with the possibility of wider application for the quantification of gallic acid as a flavor and visually relevant parameter in winemaking.

The problem of increasing life expectancy is solved with the help of many medical and social areas. It has been established that piRNAs and miRNAs can significantly modify the expression of protein-coding genes by suppressing the translation process. The aim of this work was to establish the possibility of binding piRNAs and miRNAs with mRNA of the KLOTHO and FGF23 genes, which promote health and increase life expectancy through participation in key metabolic processes. We used the MirTarget program, which determines the quantitative characteristics of complementary interactions of all piRNAs and miRNAs nucleotides with mRNA of the genes. piR-44682, piR-1940042, piR-3008660, piR-3215034, piR-6885965, piR-7980636 and one miRNA (ID00756.3p-miR) binding to the mRNA of the KLOTHO gene were found in one cluster of binding sites (BSs). piRNA-6890096 interacted with the mRNA of KLOTHO gene in a fully complementary manner using only canonical nucleotides. Among 17494 human genes, target genes interacting with five piRNAs that bind to the mRNA of KLOTHO gene were identified. mRNA of the AFF2, BCL2L11, CPT1A, DAZAP1, NDRG3, SKIDA1, WBP4, ZIC5, ZSWIM6 genes interacted with piR-3215034 and piR-6885965, which formed clusters of BSs located in 5'UTR, CDS and 3'UTR. The piR-576442, piR-1501557, piR-1845735, piR-2069834, and piR-3029987 had BSs in the mRNAs of the FGF23 gene, located only in the 3'UTR. It is proposed to use piRNAs and miRNAs as regulators of the expression of KLOTHO and FGF23 anti-aging genes.

Saif et al. (J. Math. Comput. Sci. 21 (2020) 127-135) considered modified Laplace transform and developed some of their certain properties and relations. Motivated by this work, in this paper, we define modified Sumudu transform and investigate many properties and relations including modified Sumudu transforms of the power function, sine, cosine, hyperbolic sine, hyperbolic cosine, exponential function, and function derivatives. Moreover, we attain two shifting properties and a scale preserving theorem for the modified Sumudu transform. We give modified inverse Sumudu transform and investigate some relations and examples. Furthermore, we show that the modified Sumudu transform is the theoretical dual transform to the modified Laplace transform.

Pharmacovigilance databases are showing evidence of injury in the context of the COVID-19 modified mRNA shots. According to recent publications, adverse event reports linked to the mRNA COVID-19 products largely point to the spike protein as an aetiological agent of adverse events, but we propose that the platform itself may be culpable. To assess the safety of current and future mRNA vaccines, further analysis on the risks due to the platform itself, and not specifically the expressed antigen. If harm can be exclusively and conclusively attributed to the spike protein, then it is possible that future mRNA vaccines expressing other antigens will be safe. If harms are attributable to the platform itself, then regardless of the toxicity, or lack thereof, of the chosen payload therein, the platform may be inherently unsafe, pending modification. In this work, we examine previous studies of RNA-based delivery by a lipid nanoparticle and break down the possible etiological elements of harm.

Rationale: Genetically modified (GM) foods have the potential to reduce food insecurity and address economic and environmental issues. Despite these benefits, GM foods continue to face significant criticism and there is limited information on public awareness and understanding of their nutritional and environmental health benefits in Nigeria. This study aims to fill this gap by investigating public knowledge and perceptions of GM foods in Victoria Island, Lagos. Methods: A convenience sampling method was used to recruit 369 respondents from Victoria Island, Lagos. Data were gathered using a structured questionnaire. The target population comprised employed adults either residing or working on Victoria Island. Statistical analyses were conducted to examine the relationship between sociodemographic factors and awareness of GM foods. Results: The study found that a majority of respondents (62.9%, n=232) were knowledgeable about GM foods and their associated issues. However, many believed that their community was not well-informed on the topic. Awareness of GM foods was significantly associated with sociodemographic factors such as marital status and education (P<0.01). Most respondents were well-informed about the environmental and health benefits of GM foods, with 61.8% believing that GM food production could sustainably reduce reliance on chemical pesticides, fertilizers, and other energy inputs, thus mitigating their ecological impacts. Additionally, most respondents did not feel that purchasing or consuming GM foods conflicted with their beliefs or would affect their food choices. Conclusion: The study concludes that while individual awareness of GM foods is relatively high, there is a perception that community awareness is low. Sociodemographic factors play a significant role in shaping public awareness and perceptions of GM foods. Recommendations: This includes government should actively educate the public on the ecological and health benefits of GM foods and address any safety concerns; Implement strict border controls and food labeling for GM products to protect consumer rights and preferences for organic foods, provide sufficient technical and financial assistance to farmers who participate in organic seed programs to enhance national food security. Significant Statement: This study highlights the importance of public education on GM foods and underscores the need for government intervention to ensure informed consumer choices and support for sustainable agricultural practices.

Here, we present a staged approach for an innovative repurposing of a portable infant humidicrib into a live cell growth, observation, and imaging system. Furthmore, humidicrib can support different variations of “umbilical” bioreactors, and can be used to conduct electrophysiology experiments and in situ immunohistochemistry. Modifications incorporate a closed loop carbon dioxide (CO₂) concentration control system with umbilical CO₂ and heating support for tailored bioreactors. The repurposing cost is inexpensive and allows for the continued observation and imaging of cells. This prototype unit has been used to continuously observe and image live primary neurons for up to 21 days. This demonstrates the repurposed units’ suitability for use in tissue culture based research, particularly where modifications to microscopes are required or where sensitive manipulation outside of a standard incubator is needed.

The recent setbacks in the withdrawal and approval delays of antibody treatments of neurodegenerative disorders (NDs) can be attributed to their poor entry across the blood-brain barrier (BBB). While several invasive and noninvasive approaches can be used to make the BBB more permeable, their inconsistency makes them a poor choice; however, if an antibody is chemically modified to attach a transferrin molecule that enhances its permeation across the BBB, this could be the most practical and useful modification that can transform the science of ND treatment. Antibodies can be conjugated with transferrin in vitro, but preferably through mRNA, as we propose to convert current treatments to bring faster treatment options. The mRNA technology yields products at a meager cost, which is a consideration for the affordability of these drugs globally. This paper provides complete details with templates to convert the current medicines and those under development into mRNA delivery systems to ensure clinical success, avoiding the current failures in their efficacy, more specifically the products that have demonstrated efficacy but are being removed from the market.

Each injection of any known vaccine results in a strong expression of pro-inflammatory cytokines. This is the result of the innate immune system activation, without which no adaptive response to the injection of vaccines is possible. COVID-19 mRNA vaccines would not escape this rule. Unfortunately, the degree of inflammation produced by these vaccines is variable, probably depending on the genetic background and previous immune experiences, which through epigenetic modifications, could have made the innate immune system of each individual tolerant or reactive to subsequent immune stimulations.We hypothesize that we can move from a limited pro-inflammatory condition to conditions of increasing expression of pro-inflammatory cytokines that can culminate in multisystem hyperinflammatory syndromes following COVID-19 mRNA vaccines (MIS-V). We have graphically represented this idea in a hypothetical inflammatory pyramid (IP) and we have correlated the time factor to the degree of inflammation produced after the injection of vaccines. Furthermore, we have placed the clinical manifestations within this hypothetical IP, correlating them to the degree of inflammation produced. Surprisingly, excluding the possible presence of an early MIS-V, the time factor and the complexity of clinical manifestations are correlated to the increasing degree of inflammation: symptoms, heart disease and syndromes (MIS-V).

Extracellular vesicles (EVs) can transfer diverse RNA cargo for intercellular signalling. EV-associated RNAs have been found in diverse fungi and were proposed to be relevant for pathogenesis in animal hosts. In plant-pathogen interactions, small RNAs are exchanged in a cross-kingdom RNAi warfare and EVs were considered to be a delivery mechanism. To extend the search for EV-associated molecules involved in plants-pathogen communication, we have characterised the repertoire of EV-associated mRNAs secreted by the maize smut pathogen, Ustilago maydis. For this initial survey, EVs were isolated from axenic filamentous cultures that mimic infectious hyphae. The EV-associated RNAs were resistant to degradation by RNases and the presence of intact mRNAs was evident. The set of mRNAs enriched inside EVs relative to the fungal cells are functionally distinct from those that are depleted from EVs, particularly overrepresented in metabolic enzyme activities. Intriguingly, mRNAs of some known effectors and other proteins linked to virulence were found in EVs. Furthermore, several mRNAs enriched in EVs are also upregulated during infection, suggesting that EV-associated mRNAs may participate in plant-pathogen interaction.

This review will explore the four major pillars required for design and development of an saRNA vaccine: antigen design, vector design, non-viral delivery systems, and manufacturing (both saRNA and lipid nanoparticles (LNP)). In will report on the major innovations, preclinical and clinical data reported in the last five years and will discuss future prospects.

The collection of forty-nine 8-hydroxyquinoline derivatives, substituted at C5, C6 or C7, was designed and studied by computational methods of modified POM analysis, using SwissADME, Osiris and Molinspiration tool. POM analysis (Petra/Osiris/Molinspiration) and its modified version using SwissADME instead of Petra software are indisputably tools of modern chemoinformatics, often published in the professional literature as well as in the field of research of new antibacterial active compounds, developed to replace existing antibiotics that fail due to increased resistance of bacteria. NitroxolineTM and the group of 8-hydroxyquinoline derivatives with their broad antibacterial effect and the possibility of extensive derivatization of the skeleton, represent a promising direction in the research of new antibacterial active substances. Twenty 8-hydroxyquinoline derivatives were also evaluated on their antibacterial activity against eight selected G+ and G- bacterial strains with a defined resistance mechanism. All structures were in accordance with Lipinski's criteria, twenty-one structures were interesting from the point of view of individual or average value of the bioactivity prediction score and fourteen structures showed one or more mechanisms of toxicity prediction. Furthermore, eleven structures showed a low rate of GI absorption or the inability to cross the BBB barrier, fourteen substances showed a BRENK or PAIN warning, eleven substances are an undesirable substrate of P-glycoprotein and all structures predicted the same level of bioavailability and a relatively low rate of metabolism in the liver. Five structures were selected by the intersection of the POM criteria. The virtual structures 17, 25, 35 and 43 can be favored for the continuity of next study. The resulting scores of bioactivity can indicate the potential of studied structures to be used for the design and development of new active antibacterial agents.

The space time fractional Korteweg-de Vries equation, modified Equal Width equation and Benney-Luke Equations are solved by using simple hyperbolic tangent Ansatz method. A simple compatible wave transformation in one dimension is employed to reduce the governing equations to integer ordered ODEs. Then, the ansatz approximation is used to derive exact solutions. Some illustrative examples are presented for some particular choices of parameters and derivative orders.

ABSTRACT. In this paper, we suggest a biomathematical numerical method for analysing mRNA nucleotides sequences based on UA/CG Fibonacci numbers proportions. This method is used to evaluate then compare the spike genes related to the main SARS-CoV2 VARIANTS currently circulating within the world population. The 10 main results proposed to be reproduced by peers are: 1/ SARS-CoV2 genome and spike evolution in one year 2020-2021. 2/ SARS-CoV2 Origins. 3/ Comparing 11 reference variants spikes. 4/ analysing 32 CAL.20C California variant patients spikes. 5/ Toward a meta mRNA Fibonacci gene end message code. 6/ Analysing S501 UK, S484 South Africa and « 2 mutations » INDIA variants. 7/ Suggesting a possible variants spike mRNA palindrome symmetry metastructure improving mRNA stability then infectiousness. 8/ Analysing Fibonacci Metastructures in the mRNA coding for the vaccines PFIZER and MODERNA. 9/ Does the CG-rich modification of the synonymous codons of the spikes of the 2 mRNA vaccines affect the expression and quantity of SARS-CoV2 antibodies? 10/ The exceptional case of the Brazilian variant P.1. Particularly, we suggest the following conjecture at mRNA folding level : CONJECTURE of SARS-CoV2 VARIANTS: The growth of long Fibonacci structures in the shape of "podiums" for almost all of the variants studied (UK, California, South Africa, India, etc.) suggests the probable folding of the Spike mRNA in the form of a "hairpin", which can strengthen the cohesion and the lifespan of this mRNA. Finally, we show that these kinds of Fibonacci matastructures disapear TOTALLY by analysing the published mRNA sequences of PFIZER and MODERNA vaccines. One fact is certain, the two mRNAs of the Moderna and Pfizer vaccines will result in a low functionality of the spike vaccine. This is because their designers by seeking greater stability, have doped to build CG rich sequences which, as soon as they are inserted into the human host, will, paradoxically, seek to mutate, like SARS-CoV2 variants, towards CG ==> UA forms in order to improve their STABILITY and LIFETIME. We conclude using new biomathematics theoretical methods (Master code and numerical standing waves), and comparing the Spikes of the two vaccines Moderna and Pfizer, that there will be very probable differences in stability and shelf life of the two respective mRNAs vaccines. However, “State of the Art” analyzes will disclose that their two protein sequences are strictly identical. By modified their synonymous codons using different strategies, no one can guarantee that the quantity of antibodies generated will be identical in the two cases. We wish to draw attention to the great ADAPTATION power - at the global scale of their genomes - of the most infectious VARIANTS, such as the BRAZIL 20J / 501Y.V3 variant (P.1). This is very worrying for the VACCINES <==> VARIANTS run: We demonstrate how the Brazilian variant P.1 which becomes uncontrollable in Brazil in April 2021 has a level of organization of long metastructures of 17,711 bases covering the genome which is 3.6 more important than that of the 2 reference genomes SARS-CoV2 and worldwide D614G. We suggest that this high level of overall structure of this variant contributes to the stability of this genome and, might explain its greater contagiousness.

A viable radiation dominated era in the early universe is best described by the standard (FLRW) model of cosmology. In this short review, we demonstrate reconstruction of the forms of F(R) in the modified theory of gravity, and the metric compatible F(T) together with the symmetric F(Q) in alternative teleparallel theories of gravity from different perspectives, primarily rendering emphasis on a viable FLRW radiation era. Inflation has also been studied for a particular choice of the scalar potential. The inflationary parameters are found to agree appreciably with the recently released observational data.

The emergence of mRNA vaccines for SARS-CoV-2 has opened a new page in vaccine development; nevertheless, concerns of the experts have been expressed about unintentional side effects on the gut microbiota (GM). Previous studies showed that this virus acts as a bacteriophage, which infects and destroys specific bacterial strains in the GM. The present manuscript hypothesizes that the synthetic spike protein could create changes in the composition and the functioning of the GM by entering the intestinal cells after vaccination and impairing the symbiotic relationship between intestinal cells and the GM. An experimental protocol to test the hypothesis is suggested.

Background: The modified Duke index derived from coronary computed tomography angiography (CCTA) was designed to predict cardiovascular outcomes based on the severity of coronary ste-nosis. However, it does not take into consideration the presence or severity of peri-coronary in-flammation. The peri-coronary fat attenuation index (FAI) is a novel imaging marker determined by CCTA which reflects the degree of inflammation in the coronary tree in patients with coronary artery disease. Purpose: To assess the association between the modified Duke index assessed by CCTA, cardiovascular risk factors and peri-coronary inflammation in the coronary arteries of pa-tients with coronary artery disease. Methods: One hundred seventy-two patients who underwent CCTA for typical angina were assigned into two groups based on the modified Duke index: group 1 – patients with low index ≤ 3 (n=107) and group 2 – patients with high index > 3 (n=65). Demo-graphic, clinical and CCTA data were collected for all patients, and FAI analysis of coronary in-flammation was performed. Results: Patients with increased values of the modified Duke index were significantly older compared to those with a low index (61.83 ± 9.89 vs. 64.78 ± 8.9; p = 0.002). No differences were found between the two groups in terms of gender distribution, hypertension, hypercholesterolemia or smoking history (all p > 0.5). The FAI score was significantly higher in patients from group 2, who presented a significantly higher score of inflammation compared to the patients in group 1, especially at the level of the right coronary artery (FAI score 20.85 ± 15.80 vs. 14.61 ± 16.66; p = 0.01 for the right coronary artery, 13.85 ± 8.04 vs. 10.91 ± 6.5; p = 0.01 for the circumflex artery, and 13.26 ±10.18 vs. 11.37 ± 8.84; p = 0.2 for the left anterior descending artery). CaRi-Heart® analysis identified a significantly higher risk of future events among patients with a high modified Duke index (34.84 % ± 25.86 % versus 16.87 % ± 15.80 %; p

In this paper, carbon nanotubes modified screen-printed electrode (CNTs/SPE) was prepared and the CNTs/SPE was employed for the electrochemical determination of antioxidant substance Chlorogenic acids (CGAs). A pair of well-defined redox peak of CGA was observed at the CNTs/SPE in 0.10 mol∙L^-1 acetic acid-sodium acetate buffer (pH 6.2) and electrode process is adsorption-controlled. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) method for the determination of CGA were proposed based on the CNTs/SPE. Under the optimal conditions, the proposed method exhibited linear ranges from 4.73×10^-7 to 4.45×10^-5 mol∙L^-1, the linear regression equation was Ipa(µA) = 4.1993 C (mol∙L^-1)+1.1039 (r = 0.9976) and the detection limit for CGA could reach 3.25×10^-6 mol∙L^-1. The recovery of matrine was 94.74~106.65% (RSD = 2.92%) in coffe beans. The proposed method is quick, sensitive, reliable, and can be used for the determination of CGA.

The coronavirus disease (COVID-19) is a respiratory tract infection caused by the new virus SARS-CoV-2. In March 2020, the World Health Organization (WHO) declared a worldwide COVID-19 pandemic. Since then, there has been a rush to find preventative or curative treatment. This arrived with the appearance of the COVID-19 vaccine, months after the declaration of the pandemic. In the setting of global COVID-19 immunization, there have been reports of rare skin immune-mediated diseases (IMD) after COVID-19 vaccination, particularly systemic sclerosis. Systemic sclerosis (SSc) is the most reported new onset IMD following messenger RNA (mRNA) COVID-19 vaccination. The pathogenesis of SSc is not fully understood, and the diagnosis is based on clinical symptoms. We report a 54-year-old male, with no prior history of autoimmune disorder, with rapid and progressive skin thickening (Modified Rodnan skin score 30/51), weeks after his mRNA COVID-19 vaccination. Antinuclear antibodies (ANA) showed a strongly positive nuclear fine-speckled pattern, but no SSc autoantibodies were found. The patient was diagnosed with SSc based on the persistence of autoantibodies and the clinical criteria according to the 2013 American College of Rheumatology/European League Against Rheumatism classification. Due to the proximity of the two events, we hypothesized a cross-reaction between COVID-19 vaccination and, in genetically predisposed patients, an emergence of systemic sclerosis. Our case suggests a potential relationship between the mRNA COVID-19 vaccine and new-onset autoimmune diseases. Physicians should be aware of this possible association.

Cellular biomolecular condensates termed ribonucleoprotein (RNP) granules often are enriched in messenger RNA (mRNA) molecules relative to the surrounding cytoplasm. Yet, the spatial localization and diffusion of mRNAs in close proximity to phase separated RNP granules is not well understood. In this study, we performed single molecule fluorescence imaging experiments of mRNAs in live cells in the presence of two types of RNP granules, stress granules (SG) and processing bodies (PB), which are distinct in their molecular composition and function. We developed a photobleaching- and noise-corrected colocalization imaging algorithm that was employed to determine the accurate positions of individual mRNAs relative to the granule’s boundaries. We found that mRNAs are often localized at granule boundaries, an observation consistent with recently published data. We suggest that mRNA molecules become spontaneously confined at the RNP granule boundary similar to the adsorption of polymer molecules at liquid-liquid interfaces, which is observed in various technological and biological processes. We also suggest that this confinement could be due to a combination of intermolecular interactions associated with, first, the screening of a portion of the RNP granule interface by the polymer and, second, electrostatic interactions due to a strong electric field induced by a Donnan potential generated across the thin interface.

Vaccines based on mRNA-containing lipid nanoparticles (LNPs) pioneered by Katalin Karikó and Drew Weissman at the University of Pennsylvania are a promising new vaccine platform used by two of the leading vaccine candidates against coronavirus disease in 2019 (COVID-19). However, there are many questions regarding their mechanism of action in humans that remain unanswered. Here we consider the immunological features of LNP components and off-target effects of the mRNA, both of which could increase the risk of side effects. We suggest ways to mitigate these potential risks by harnessing dendritic cell (DC) biology.

The turnover of the RNA molecules is determined by the rates of transcription and RNA degradation. Several methods have been developed to study mRNA turnover since the beginnings of molecular biology. Here we summarize the main methods to measure RNA half-life: transcription inhibition, gene control and metabolic labelling. These methods were used to detect the cellular activity of the mRNAs degradation machinery, including the exo-ribonuclease Xrn1 and the exosome. Less progress has been made in the study of the differential stability of mature RNAs because the different methods have often yielded inconsistent results so that an mRNA considered to be stable can be classified as unstable by another method. Recent advances in the systematic comparison of different method variants in yeast have permitted the identification of the least invasive methodologies that reflect half-lives the most faithfully, which is expected to open the way for a consistent quantitative analysis of the determinants of mRNA stability.

To screen and validate immunosuppressive factors in luminal- and basal-like breast cancer cell lines and tissue samples associated with malignant phenotypes. The mRNA microarray datasets, GSE40057 and GSE1561, were downloaded and remodelled. Differentially expressed genes (DEGs) were identified. Enrichment analyses performed and the online resources, GOBO and Kaplan-Meier Plotter, were employed to screen for immunosuppressive factors associated with breast cancer malignant phenotypes. qRT-PCR and western blot were used to validate the expression of CD274 and IL8 in cell lines and immunohistochemical detected the MIF and VEGFA on tissue microarrays. The results showed that CD274 and IL8 were both upregulated in basal-like cell lines. That MIF expression was dramatically increased in patients with breast cancer metastases (p<0.05) and that VEGFA expression positively correlates with breast cancer pathologic grade (p<0.05).During the formation and development of breast cancer, immune-related genes are always activated, and immunosuppressive factors CD274, IL8, MIF and VEGFA are upregulated. Such molecules could be used as biomarkers for breast cancer prognosis. However, because individual immune-related factors can play several biological roles, the mechanistic relationship between immunosuppressive factors and breast cancer malignant phenotypes and the feasibility of their application as drug targets require further investigation.

Cloud data centers play a vital role in modern computing infrastructure, offering scalable resources for diverse applications. However, managing costs and resources efficiently in these centers has become a crucial concern due to the exponential growth of cloud computing. User applications exhibit complex behavior, leading to fluctuations in system performance and increased power usage. To tackle these obstacles, we propose the consolidation of virtual machines (VMs) to optimize resource utilization and reduce operational costs. This paper introduces a novel algorithm, leveraging the Modified Artificial Feeding Birds Algorithm (ModAFBA), to manage cost optimally in cloud data centers by reducing power usage while meeting service level agreements (SLAs). The ModAFBA algorithm, inspired by bird foraging behavior, dynamically adjusts solutions based on environmental changes. Comprehensive experimental evaluation demonstrates the superiority of the proposed algorithm in terms of power usage, migration count, and SLA compliance. Through this research, we aim to advance cost management and resource optimization in cloud data centers, providing a valuable tool for cloud service providers to enhance infrastructure efficiency and achieve cost savings.

The advancement of performance in the domain of flexible wearable strain sensors has become increasingly significant due to extensive research on laser-induced graphene (LIG). An innovative doping modification technique is required owing to the limited progress achieved by adjusting laser parameters to enhance LIG’s performance. By pre-treating with AgNO3, we successfully manufactured LIG with a uniform dispersion of silver nanoparticles across its surface. The experimental results for the flexible strain sensor exhibit exceptional characteristics, including low resistance (183.4 Ω), high sensitivity (426.8), a response time of approximately 150 ms, and a relaxation time of about 200 ms. Moreover, this sensor demonstrates excellent stability under various tensile strains and remarkable repeatability during cyclic tests lasting up to 8,000 s. Additionally, this technique yields favorable results in finger bending and hand back stretching experiments, holding significant reference value for preserving the inherent characteristics of LIG preparation in a single-step and in situ manner.

The new class of mRNA vaccines is studied extensively, leading to many novel prospects based on the pivotal success of vaccines against the SARS-Cov-2 virus. Many novel mechanisms of immune response discovered have led to the possibility of mutation-resistant vaccines by combining multiple conserved epitopes as antigens to manipulate the T-cell and B-cell responses; these antigens can also come from different organisms, providing protection against numerous diseases and of most tremendous significance is the utility of mRNA vaccines in preventing and treating more than 100 autoimmune disorders. This is a significant humanitarian breakthrough given the ease and faster and low cost of mRNA vaccines, being a chemical entity. This paper provides a prospective analysis of mRNA vaccines with much broader applications than anticipated when these vaccines entered treating SARS-Cov-2 infections.

The study assessed the trapping efficacy of locally-modified 1) Gravid Aedes Trap(GAT) lined with insecticide-treated net (ITN) as a killing agent, 2) Autocidal Gravid Ovitrap(AGO) with sticky board in the semi-field system (SFS) and field setting. Fully-balanced Latin square experiments were conducted to compare GAT lined with ITN vs AGO, both with either yeast or grass infusion. Biogents-Sentinel (BGS) with BG-Lure and no CO2 was used as standard trap for Aedes mosquitoes. In the SFS, GAT outperformed AGO in collecting both nulliparous (65% vs 49%,OR=2.22,[95%CI:1.89-2.60],p

The aim of this study is to analyze the characteristics of drought such as intensity, cumulative curves and trends, based on SPEI (Standardized Precipitation Evapotranspiration Index) at 8 stations in Korea from 1981 to 2010. The traditional SPEI is based on Thornthwaite equation for estimating evapotranspiration; SPEI_th. However, a standard of agricultural water management in Korea suggests FAO Penman-Monteith equation; SPEI_pm. In this study, we analyzed the intensity and trends of drought using SPEI_th and SPEI_pm, respectively, and analyzed the relationship between them. Both of central and southern region, the SPEIs were below -1.0 (moderated drought) for the periods May-August in the representative drought year such as 1988, 2001, and 2008-09. The frequency of drought was higher in southern region than central region. In addition, SPEI_pm showed slightly more intensive drought rather than SPEI_th except for Chuncheon and Gwangju. In 5 stations except for Cheoncheon, Gwangju and Jinju, the cumulative probability that SPEI_pm is below -1.5 was significantly increased from 1981-1995 to 1996-2010. As the results of drought trends, the increasing trend of SPEIs was shown on fall season, and the cumulative probability that SPEI_pm is below -1.5 was also significantly increased.

The surface thermodynamic properties of polymers and copolymers modified by supramolecular structures are very used in several industrial processes, such as selective adsorption, paints, coatings, colloids, and adhesion applications. Background: Inverse gas chromatography at infinite dilution was proved to be the best technique to determine the surface properties of solid surfaces by studying the adsorption of some model polar and non-polar organic molecules adsorbed on solid surfaces by varying the temperature. Methods: The retention volume of adsorbed solvents is a precious parameter to obtain the London dispersive and polar free energies and the London dispersive surface energy of styrene–divinylbenzene copolymer modified by supramolecular structure of melamine using the Hamieh thermal model and our new methodology consisting in the separation of the two polar and dispersive free energy of interaction. This led to the determination of the polar acid and base surface energy, and the Lewis’s acid-base constants of the various solid materials. Results: all surface energetic properties of styrene–divinylbenzene copolymer modified by melamine at different percentages were determined as a function of temperature, following our new methodology. Conclusions: It was observed that the styrene–divinylbenzene copolymer exhibited the highest London dispersive surface energy which decreased when the melamine percentage increased. All materials presented higher Lewis’s basicity and this Lewis’s basicity increased with the percentage of melamine.

The three dimensional conformable time fractional Kadomtsev-Petviashvili and the conformable time fractional modified Kawahara equations are solved by implementing the Kudryashov's procedure. The corresponding wave transformation reduces both equations to some ODEs. Balancing the nonlinear and the highest order derivative terms gives the structure of the solutions in the finite series form. The useful symbolic tools are used to solve the resultant algebraic systems. The solutions are expressed in explicit forms.

Nucleic acid delivery through extracellular vesicles (EVs) is a well-preserved evolutionary mechanism in all life kingdoms including eukaryotes, prokaryotes, and plants. EVs naturally allow horizontal transfer of native as well as exogenous functional mRNA, that once incorporated in EVs is protected from enzymatic degradation. The possible use of EVs as carriers for vaccine has been investigated showing that EVs expressing recombinant SARS-CoV-2 S protein induced an immune response. Moreover, EV-based vaccines presenting the natural configuration of viral antigens have advantages in conferring long lasting immunization and lower toxicity than synthetic nanoparticles. To overcome the manufacturing limitations of EVs derived from eukaryotic cells, edible plant-derived EVs have been studied as an attractive alternative for vaccine delivery, especially for mucosal administration. We recently showed that EVs obtained from orange juice (oEVs) loaded with SARS-CoV-2 mRNAs protected their cargo from enzymatic degradation and were stable at room temperature for one year. Lyophilized oEVs containing the S1 mRNA were administered to rats by gavage and they induced a specific humoral immune response with generation of blocking antibodies, including IgA, that are the first mucosal barrier in the adaptive immune response. Moreover, a Th1 cytokine secretion occurred, suggesting a specific lymphocyte activation. In conclusion, mRNA-containing oEVs could be used for developing new oral vaccines due to optimal mucosal absorption, resistance to stress conditions, and the ability to stimulate a humoral and cellular immune response.

Creating transgenic insects is a key technology in insect genetics and molecular biology. A widely used instrument in insect transgenesis is the piggyBac transposase, resulting in essentially ran-dom genomic integrations. In contrast, site-specific recombinases allow the targeted integration of the transgene construct into a specific genomic target site. Both strategies, however, often face limitations due to low transgenesis rates. We aimed to enhance transgenesis rates by utilizing a capped mRNA as a source of transposase or recombinase instead of a helper plasmid. A system-atic comparison of transgenesis rates in Aedes mosquitoes, as models for hard to transform in-sects, showed that suppling piggyBac transposase as mRNA increased the average transfor-mation efficiency in Aedes aegypti from less than 5% with the plasmid source to about 50% with mRNA. Similar high transformation activity was observed in Ae. albopictus with pBac mRNA. No efficiency differences between plasmid and mRNA were observed in recombination experi-ments. Furthermore, a codon-optimized version of piggyBac transposase delivered as plasmid didn’t improve the transformation efficiency in Ae. aegypti or the agricultural pest D. suzukii. We believe that the use of mRNA has strong potential for enhancing pBac transformation efficiencies in other mosquitoes and important agricultural pests such as tephritids.

Currently available COVID-19 mRNA vaccines have demonstrated high efficacy in clinical trials.1-3 However, cancer patients, including those with hematological malignancies, were largely excluded from these trials. In this prospective, observational study we measured anti-S protein IgG titers as well as avidity in lymphoma patients (n=67) vaccinated with a COVID-19 mRNA vaccine. Serological response rates in lymphoma patients who were treatment naïve (100% in CLL, 88.9% in other, non-CLL non-Hodgkin lymphoma patients), or who were last treated more than 24 months prior to vaccination (100% in CLL, 90% in other-NHL), were similar to healthy controls (100%). Patients on active therapy, however, had a diminished response rate (40% in CLL, 21.0% in other-NHL). No patient who received anti-CD20 monoclonal antibodies (mAb) within six months of vaccination responded. Thus, the utility of testing anti-S titers should be explored in patients on active therapy or with recent anti-CD20 mAb exposure, to assess their response to vaccination. We also propose studying passive protection with S-protein mAbs as an alternative prophylactic strategy for patients who respond poorly to vaccination.

Multiple mRNA isoforms of the same gene are produced via alternative splicing, a biological mechanism that regulates protein diversity while maintaining genome size. Alternatively spliced mRNA isoforms of the same gene may sometimes have very similar sequence, but they can have significantly diverse effects on cellular function and regulation. The products of alternative splicing have important and diverse functional roles, such as response to environmental stress, regulation of gene expression, human heritable and plant diseases. The mRNA isoforms of the same gene, such as the apoptosis associated CASP3 gene, can have dramatically different functions. The shorter mRNA isoform product CASP3-S inhibits apoptosis, while the longer CASP3-L mRNA isoform promotes apoptosis. Despite the functional importance of mRNA isoforms, very little has been done to annotate their functions. The recent years have however seen the development of several computational methods aimed at predicting mRNA isoform level biological functions. These methods use a wide array of proteo-genomic data to develop machine learning-based mRNA isoform function prediction tools. In this review, we discuss the computational methods developed for predicting the biological function at the individual mRNA isoform level.

Stroke survivors often face diverse unmet needs, highlighting the significance of identifying and addressing these needs to enhance rehabilitation outcomes and overall quality of life. This study aimed to validate the modified Needs Assessment Questionnaire (mNAQ) as a reliable and valid tool for assessing the needs of stroke patients in the Greek context. Additionally, the research sought to identify potential differences in the assessment of stroke patients' needs based on their stroke phase and National Institutes of Health Stroke Scale (NIHSS) scores. A sample of 71 adult stroke survivors, adhering to World Health Organization guidelines and providing autonomous consent, participated in the study. The mNAQ, comprising 141 items across 12 domains, was uti-lized to evaluate stroke patients' needs. The NIHSS and Barthel Index (BI) were employed for functional independence and mobility assessment. Data analysis incorporated confirmatory fac-tor analysis, exploratory factor analysis, and Cronbach's reliability analysis to establish con-struct validity and internal consistency. Concurrent and known-groups validity analyses were conducted, and Spearman’s rho correlation explored the relationship between mNAQ and BI scores. Non-parametric analyses were applied to identify differences based on stroke phase and NIHSS scores. The study revealed that the mNAQ initially lacked satisfactory psychometric properties in the Greek context. Subsequent modifications, guided by confirmatory and explora-tory factor analyses, resulted in a refined three-factor scale encompassing 31 items in the domains of communication, mobility, and social functioning needs. This adapted measure effectively dif-ferentiated between acute and chronic stroke patients and those with minor and moderate strokes. In conclusion, the validated 31-item Greek mNAQ emerges as a crucial tool for compre-hensively assessing the needs of stroke patients. Its application holds promise for optimizing post-stroke care, improving functional outcomes, and ultimately enhancing the overall well-being and quality of life for stroke survivors.

The intricate mechanisms of the immune response elicited by vaccines and the interplay between the immune system and the central nervous system (CNS) are poorly understood. This review explores these mechanisms, emphasizing the interplay between the immune system and the central nervous system (CNS). A critical aspect is the examination of how vaccine-induced immune responses can interact with the CNS, influencing neuroinflammation and neuroimmune interactions. Furthermore, the link between vaccination and persistent symptoms observed in long-COVID patients is discussed. Vaccination initiates a complex cascade of events, starting with the production of specific proteins, such as S1/S2 spike proteins, leading to robust immune activation in the axillary lymph nodes. The role of macrophages and antigen-presenting cells (APCs) in cytokine production, antigen presentation, and the stimulation of B and T cells highlights the sophistication of the adaptive immune response. The migration of immune cell-derived exosomes to the brain plays a dynamic role in CNS inflammation, neurodegenerative processes and long COVID. On the other hand, the prolonged presence of viral and vaccine-derived spike proteins may contribute to the complex pathophysiology of Long-COVID, shedding light on the delicate balance between beneficial immune responses and possible adverse neurological outcomes of vaccination. It is worth rigorous monitoring and further research to understand the mechanisms of neuroinflammation and the persistence of spike proteins and their long-term effects on the brain, emphasising the importance of a nuanced approach to vaccine safety and efficacy in the context of COVID-19 and beyond.Principio del formulario

Multiple myeloma (MM) is a genetically complex disease that results from a multistep transformation of normal to malignant plasma cells in the bone marrow. However, the molecular mechanisms responsible for the initiation and heterogeneous evolution of MM remain largely unknown. A fundamental step needed to understand the oncogenesis of MM and its response to therapy is the identification of driver mutations. The introduction of gene expression profiling (GEP) in MM was an important step in elucidating the molecular heterogeneity of MM and its clinical relevance. Since some mutations in myeloma occur in non-coding regions, studies based on the analysis of mRNA provide more comprehensive information on the oncogenic pathways and mechanisms relevant to MM biology. In this review, we discuss the role of gene expression profiling in understanding the biology of multiple myeloma together with the clinical manifestation of the disease, as well as its impact on treatment decisions and future directions.

Fatigue performance and self-repairing activity of asphalt binders are two properties that highly influence the fatigue cracking response of asphalt pavement. There are still numerous gaps of knowledge to fill linked with these two characteristics. For instance, current parameters fail to fully accommodate these two bitumen phenomena. This study aims to propose a new procedure to address this issue utilizing the linear amplitude sweep (LAS) test, LAS with rest period (RP) (LASH) test, and simplified viscoelastic continuum damage (S-VECD) model. This research work used four different types of asphalt binders: neat asphalt (NA), self-healing thermoplastic polyurethane (STPU)-modified bitumen (STPB), self-healing poly (dimethyl siloxane) crosslinked with urea bond (IPA1w)-modified bitumen (IPAB), and styrene–butadiene–styrene (SBS)-modified bitumen (SBSB). Before the testing process, all the materials were subjected to short-term and long-term aging. The new procedure showed a superior capacity to analyze and accommodate all bitumen fatigue performances and self-repairing activities compared to the current method. Another finding proved that asphalt binders with higher self-restoration behavior failed to show better fatigue performance. A breakthrough finding demonstrated that asphalt binder fatigue response augmented when the RP was applied at a higher damage intensity (S) value. STPBs and IPABs reached their highest increments of fatigue response, containing 1.0% of STPU and 0.5% of IPA1w, respectively. Those augmentations were 207.54% and 232.64%, respectively.

The emission of toxic gases from industrial production have intensified issues related to atmospheric pollution and human health. Consequently, the effective real-time monitoring and removal of these harmful industrial gases have emerged as significant challenges. In this work, the density functional theory (DFT) method was utilized to examine the adsorption behaviors and electrical characteristics of Ni-decorated InSe (Ni-InSe) monolayer when interacting with twelve gases (CO, NO, NO2, NH3, SO2, H2S, H2O, CO2, CH4, H2, O2 and N2). A comparative assessment of adsorption strength and sensing properties was performed through analyses of electronic structure, work function and recovery time. The results show that Ni doping enhances the electrical conductivity of the InSe monolayer and improves the adsorption capabilities for six toxic gases (CO, NO, NO2, NH3, SO2, H2S). Furthermore, the adsorption of these gases on the Ni-InSe surface is characterized as chemisorption, as indicated by the analysis of adsorption energy, density of states, and charge density difference. Additionally, the adsorption of CO, NO, NO2, and SO2 results in significant alterations to the bandgap of Ni-InSe, with changes of 18.65%, 11.37%, 10.62%, and –31.77%, respectively, underscoring its exceptional sensitivity. Moreover, the Ni-InSe monolayer exhibit moderate recovery times of 3.24 s and 22.72 s at 298 K for the SO2 and H2S, respectively. Consequently, the Ni-InSe is regarded as a promising gas sensor for detecting SO2 and H2S at room temperature. This research establishes a foundation for developing Ni-InSe based gas sensor in detecting and mitigating harmful gas emissions.

In the present work we consider two modified Chevallier-Polarski-Linder (CPL) models in the background of homogeneous and isotropic FLRW space-time, namely (i) the generalized CPL model (Model I) and (ii) the logarithmic form of the the equation of state for the dark energy. From the observational data sets ((Pantheon+)+BAO+HST), we find that at the present epoch (redshift $z=0$), the equation of state for the dark energy converges almost at the same value $\omega_{fld}\approx -0.86$ and the variation of $\omega_{fld}(z)$ with respect to the redshift parameter is very small for both models. we also find that the present value of the Hubble parameter $H_0$ is almost same for both the models. Finally, we compare the models in the light of Akaike, Bayesian Information Criterion (BIC) and Bayesian Evidence. However, we find that Model II is better compared to the Model I from the estimated value of the deceleration parameter.

In this study organic bulk heterojunction (BHJ) solar cell along with the spiro OMeTAD as a hole transport layer (HTL) and the PDINO as an electron transport layer (ETL) was simulated through the Solar Capacitance Simulator, one dimensional (SCAPS-1D) software to examine the performance of this type of polymer thin film organic solar cells. As an active layer the blend of polymer donor PBDB-T and non-fullerene acceptor ITIC-OE was used. Numerical simulation was performed by varying the thickness of HTL and active layer. Firstly, the HTL layer thickness was optimized to 50 nm, after that the active layer thickness varied up to 80 nm. These results of simulation demonstrated that the HTL thickness has rather little impact on efficiency while in the case of active layer thickness improves efficiency significantly. The temperature effect on the performance of solar cells was considered, by the simulation performed for temperature from 300 K up to 400 K and the efficiency of solar cell decreases with increasing temperature. Generally, polymer films usually are full of traps and defects, the density of defects (Nt) value was also introduced to the simulation, and it was confirmed that with the increasing of defect density (Nt), the efficiency of solar cell decreases. After thickness, temperature and defect density optimization, the reflection coating was also applied on it. It turned out that by introducing the reflection coating on the back side of solar cell, the efficiency increases by 2.5 %. Additionally, the positive effect of HTL and ETL doping on efficiency of this type of solar cells was demonstrated.

Kim-Kim ([9]) studied some properties of the degenerate gamma and degenerate Laplace transformation and obtained their properties. In this paper, we define modified degenerate gamma and modified degenerate Laplace Transformation and investigate some properties and formulas related to them.

The presence of premature termination codons (PTCs) in transcripts is dangerous for the cell as they encode potentially deleterious truncated proteins that can act with dominant-negative or gain-of-function effects. To avoid synthesis of these shortened polypeptides, several RNA surveillance systems can be activated to decrease the level of PTC-containing mRNAs. Nonsense-mediated mRNA decay (NMD) ensures an accelerated degradation of mRNAs harboring PTCs by using several key NMD factors such as up-frameshift (UPF) proteins. Another pathway called nonsense-associated altered splicing (NAS) upregulates transcripts that have skipped disturbing PTCs by alternative splicing. Therefore, these RNA quality control processes eliminate abnormal PTC-containing mRNAs from the cells by using positive and negative responses. In this review, we will describe the general mechanisms of NMD and NAS and their respective involvement in the decay of aberrant immunoglobulin and TCR transcripts in lymphoid cells.

During one of the worst global health crises, millions of people were vaccinated against SARS-CoV-2. In rare cases, new onset systemic inflammatory diseases were reported with temporal coincidence to the vaccination. We describe a case of severe Eosinophilic Granulomatosis with Polyangiitis (EGPA) in a young asthmatic woman, occurring after a 2nd dose of mRNA-1273 vaccine. She presented with multisystem EGPA with cardiac and central nervous system involve-ment, complicated by secondary immune thrombocytopenia (ITP). We review the reported cases of EGPA coinciding with SARS-CoV-2 mRNA vaccination. All potentially vaccine-related EGPA cases reported so far occurred within 14 days from immunization. EGPA is very rare with an incidence of 1:1’000’000 inhabitants and the number of reported post-vaccination EGPA cases lies within the expected incidence rate for the period. While we cannot prove a causal relationship between the vaccine and EGPA onset, the temporal relationship with the vaccine immune stimulation is intriguing, in a disease occurring almost always in adults with asthma and/or chronic rhinosinusitis and driven by an aberrant Th2 lym-phocyte activation with hypereosinophilia. Nevertheless, cases of inflammatory diseases emerging in the context of vaccination remain rare and the benefits of preventing severe Covid presentations with SARS-CoV-2 mRNA vaccines remains unquestionable.

In the recent days, lipid nanoparticles have been successfully emerged as one of the most advanced technology for highly efficient in vivo delivery of exogenous mRNA, especially for delivery of COVID-19 vaccines. For the vaccines to be successful or protective, they require highly efficient mRNA delivery systems. However, developing effective, translatable vaccines with better safety against some of the SARS‐CoV‐2 variants is still a challenge. Lipid nanoparticles (LNPs) are composed of four different types of lipids including ionizable lipids, helper or neutral lipids, cholesterol and polyethylene glycol (PEG) attached lipids. In this review, we present recent advancements and insights in designing the advanced LNPs and their composition and properties, with a subsequent discussion on the development of COVID-19 vaccines. In particular, as the ionizable lipids are most important drivers for complexing the mRNA and in vivo delivery, the role of ionizable lipids in mRNA vaccines discussed in detail. Furthermore, the use of LNPs as effective delivery vehicles for vaccination, genome editing, and protein replacement therapy were discussed. Finally, expert opinion of LNPs for mRNA vaccines were discussed which might address the future challenges in the development of mRNA vaccines employing highly efficient LNPs using novel set of ionizable lipids.

Molecular therapies exploiting mRNA vectors embody enormous potential, as evidenced by the utility of this technology for the context of the COVID-19 pandemic. None-the-less, broad implementation of these promising strategies has been restricted by the limited repertoires of delivery vehicles capable of mRNA transport. On this basis, we explored a strategy based on exploiting the well characterized entry biology of adenovirus. To this end, we studied an adenovirus-polylysine (AdpL) that embodied “piggyback” transport of the mRNA on the capsid exterior of adenovirus. We hypothesized that the efficient steps of Ad binding, receptor-mediated entry, and capsid-mediated endosome escape could provide an effective pathway for transport of mRNA to the cellular cytosol for transgene expression. Our studies confirmed that AdpL could mediate effective gene transfer of mRNA vectors in vitro and in vivo. Facets of this method may offer key utilities to feasibilize the promise of mRNA-based therapeutics.

This study focuses on cardiovascular effects, particularly myocarditis and pericarditis events, after BNT162b2 mRNA COVID-19 vaccine injection in Thai adolescents. This prospective cohort study enrolled students from two schools aged 13–18 years who received the second dose of the BNT162b2 mRNA COVID-19 vaccine. Data including demographics, symptoms, vital signs, ECG, echocardiography and cardiac enzymes were collected at baseline, Day 3, Day 7, and Day 14 (optional) using case record forms.We enrolled 314 participants; of these, 13 participants were lost to follow up, leaving 301 participants for analysis. The most common cardiovascular effects were tachycardia (7.64%), shortness of breath (6.64%), palpitation (4.32%), chest pain (4.32%), and hypertension (3.99%). Seven participants (2.33%) exhibited at least one elevated cardiac biomarker or positive lab assessments. Cardiovascular effects were found in 29.24% of patients, ranging from tachycardia, palpitation, and myopericarditis. Myopericarditis was confirmed in one patient after vaccination. Two patients had suspected pericarditis and four patients had suspected subclinical myocarditis. Conclusion: Cardiovascular effects in adolescents after BNT162b2 mRNA COVID-19 vaccination included tachycardia, palpitation, and myocarditis. The clinical presentation of myopericarditis after vaccination was usually mild, with all cases fully recovering within 14 days. Hence, adolescents receiving mRNA vaccines should be monitored for side effects. Clinical Trial Registration: NCT05288231

The discovery of microRNAs (miRNAs) has fundamentally transformed our understanding of gene regulation. The competing endogenous RNA (ceRNA) hypothesis postulates that not only messenger RNAs but also other RNA transcripts, such as long non-coding RNAs and pseudogenes, can act as natural miRNA sponges. These RNAs influence each other’s expression levels by competing for the same pool of miRNAs through miRNA response elements on their target transcripts, thereby modulating gene expression and protein activity. In recent years, these ceRNA regulatory networks have gained considerable attention in cancer research. Several studies have identified cancer-specific ceRNA networks. Nevertheless, prior bioinformatic analyses have focused on long non-coding RNAs-associated ceRNA networks. Here, we identify an extended-ceRNA network (including both long non-coding RNAs and pseudogenes) shared across a group of four hormone-dependent (HD) cancers, i.e., prostate, breast, colorectal, and endometrial cancers, using data from The Cancer Genome Atlas (TCGA). We performed a functional enrichment analysis for differentially expressed genes in the shared ceRNA network of HD cancers, followed by a survival analysis to determine their prognostic ability. We identified two long non-coding RNAs, nine genes, and seventy-four miRNAs in the shared ceRNA network across four HD cancers. Among them, two genes and forty-one miRNAs were associated with at least one HD cancer survival. This study is the first to investigate pseudogene associated ceRNAs across a group of related cancers and highlights the value of this approach to understanding shared molecular pathogenesis in a group of related diseases.

Modern organic synthesis is majorly focused on developing environmentally benign synthetic protocols by employing green chemistry principles. Accordingly, in our recent research work, we herein report the use of modified supramolecular host cyclodextrin as an effective solid based green catalyst for accessing structurally diverse and medicinally relevant pyrimidone architectures. The catalyst and the synthesized compounds 4 (a-r) were characterized using FT-IR, NMR and GC-Mass spectroscopy. Major highlights of the reported work include: atom economical process, extremely milder reaction conditions, operational simplicity, high isolated yields, and excellent catalyst turnover number. The molecular docking studies suggest that the compound 4n has the hydrogen bonding, hydrophobic and π-pair interactions with the active site of active sites of CXT M 15 receptor.

Abstract: Cancer cells are originated by normal cells and with those share the need to be fed. Metabolic reprogramming in cancer cells is not yet fully understood although there is a vast literature suggesting that huge amounts of both energy and substrates are require for synthesis of components of new neoplastic cells so that any macronutrient may be efficiently utilized. Recently, in vitro data show that EAA supplementation promoted colon cancer cells apoptosis by enhanced autophagy. Therefore, in this study we tested in vivo the effects of matched macronutrients standard laboratory diet (control) versus EAA rich modified diet (EAArmd) in mice injected with colon cancer cells. Results of the first set of 12 animals, 6 controls and 6 EAArmd-fed, showed that controls mice develop cancer volume cancers 5 times larger and heavier than EAArmd-fed. If confirmed, these results would open new scenarios for the cancer integrate therapies.

This study aimed to investigates obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: control (n=15) and study groups (n=15) that were fed a standard (SD) and high-fat diet (HFD), respectively. After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD group exhibited increased weight gain (55.8% vs 29.2%; P< 0.001) and albuminuria (10384.04 ng/ml vs 5845.45 ng/ml; P<0.001) compared to controls. The HFD group exhibited early stages of ORG lesions, with a predominance of mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that four DE miRNAs in the kidneys of the HFD group negatively regulated the PTEN gene, which promotes podocyte endocytosis of lipids in ORG. Among these four miRNAs, miR-205 was upregulated in the urine of the HFD group. HFD-fed Wistar rats developed early stages of ORG, with a specific targetome of miRNAs and gene expression. The upregulation of miR-205 in the kidney and its isolation in urine are associated with lipid endocytosis in podocytes, which could become a plausible biomarker of the early stages of ORG and lead to future therapeutic research.

Lutein, a plant-derived xanthophyl-carotenoid, is an exceptional antioxidant and anti-inflammatory constituent found in food. Elevated concentrations of lutein found in human blood and plasma, due to high dietary intake, are beneficial against eye disease and improve cardiometabolic health. Lutein plays an important protective role against the development of neurological disorders, including Alzheimer’s disease (AD), multiple sclerosis (MS) and Parkinson’s disease (PD). It has also been shown to be beneficial for liver, kidney and respiratory health. Lutein, acting as a very strong antioxidant, can alleviate oxidative stress and downgrade reactive oxygen species (ROS). Oxidative stress is one of the key pathogenic mechanisms in post-COVID and mRNA vaccine injury syndromes. Recent in silico studies suggest that lutein and other naturally derived antioxidants, by docking at the site where the SARS-CoV-2 spike protein (SP) binds to the angiotensin enzyme type 2 (ACE2) receptor, may neutralize the SP-ACE2 interactions. Lutein can be added to a detoxification regimen to aid in clearing Spike protein and relieving symptoms. In agreement with Hippocrates’ dictum to “Let food be thy medicine,” this review establishes dietary lutein as a valuable therapy in the treatment of post-COVID syndrome, mRNA vaccine injury syndromes, and a wide range of other chronic illnesses.

During their growth, bacteria respond to complex environmental changes through equally com-plex and orderly regulatory mechanisms. sRNA has an important role as a post-transcriptional regulator in the environmental adaptation of Bacillus. In this study, we identified an sRNA Bvs091 located in the intergenic region of the Bacillus velezensis, which is widely present in the genus Bacillus and whose expression is upregulated by salt treatment. The deletion of bvs091 in B. ve-lezensis PEBA20 led to a reduced growth rate and a change in the phenotypes, with simple colony structures and low and easily degradable biofilm. Salt tolerance tests indicated that the deletion of bvs091 results in a reduced salt tolerance. galT2 mRNA is supposed to be a direct target of Bvs091 according to results obtained by using the bioinformatic method and performing qRT-PCR analysis. The microscale thermophoresis (MST) analysis showed that Bvs091 could directly bind 28‒51 bases in front of the promoter of galT2. Subsequently, the deletion of galT2 in B. velezensis resulted in increased salt tolerance. Based on the techniques of double plasmids and a half-life period, sRNA Bvs091 is confirmed as a trans-encoded sRNA that negatively regulates the mRNA expression of galT2. In brief, the trans-encoded sRNA Bvs091 acts by pairing the incomplete complementary bases of galT2 mRNA, reducing galT2 mRNA’s stability and affecting the trans-lation efficiency.

The current report represents a case of a 77-year-old man with Parkinson’s disease who died three weeks after receiving his third COVID-19 vaccination in January 2022. The patient was first vaccinated in May 2021 with the ChAdOx1 nCov- 19 vector vaccine, followed by two more doses with the BNT162b2 mRNA vaccine in July and December 2021. The family of the deceased requested an autopsy due to the ambivalent clinical features noted before death. The underlying illness (Parkinson’s disease) was confirmed by autopsy. However, no sign of a florid COVID-19 was discovered. Meanwhile, the immunohistochemical staining of the brain and heart revealed previously undiagnosed conditions. The brain, in distinctive, revealed multifocal necrotizing encephalitis with massive inflammatory lymphocyte infiltrates. In addition, the heart showed signs of serious myocarditis. Finally, immunohistochemical staining revealed that the SARS-CoV-2 spike protein was evident in the tissues investigated. Based on these immunohistochemical findings, it appears that the inflammatory changes in the patient's brain tissues are most likely the result of immunological processes. Concurrently, the absence of SARS-CoV-2 nucleocapsid-protein was evidenced, indicating that the detected spike-protein is unrelated to a SARS-CoV-2 infection. If such an infection was the cause of the spike protein, the SARS-CoV-2 nucleocapsid protein would also be detectable. As a consequence, the confirmed presence of the spike protein had to be attributed to the previous vaccination with the BNT162b2 mRNA vaccine that the deceased patient had received.

A large number of physicists now admit that quantum mechanics is a non-local theory. EPR argument and the many experiences (including recent “loop-hole free” tests) showing the violation of Bell’s inequalities seem to have confirmed convincingly that quantum mechanics cannot be local. Nevertheless, this conclusion can only be drawn inside a standard realist framework assuming an ontic interpretation of the wave function and viewing the collapse of the wave function as a real change of the physical state of the system. We show that this standpoint is not mandatory and that if the collapse is no more considered as an actual physical change, it is possible to recover locality.

The microbial contamination in food packaging have been a major concern that paved the way for the search for natural based new anti-microbial agents, such as modified α-mangostin. In the present work, twelve synthetic analogs were obtained via semi-synthetic modification of α-mangostin by Ritter reaction, reduction by palladium-carbon (Pd-C), alkylation, and acetylation. The evaluation of the anti-microbial potential of the synthetic analogs showed higher therapeutic value than the parent molecule. The anti-microbial studies proved that I E showed higher antibacterial activity whereas I I showed most significant antifungal activity. Due to their microbial properties, modified α-mangostin can be utilized as active anti-microbial agents in food packaging.

The production of biomass fly ash has been increasing every year in Europe, reaching 5.5 million tons in 2020. Biomass fly ash is not yet accepted in the standards as a substitute material for cement in mortar and concrete. In a first approach, the substitution limit of biomass fly ash is determined by comparing the mechanical strengths, fresh state properties and hardened properties of mortars produced with biomass fly ash to those of mortars produced with classical coal fly ash. Then, masonry and rendering mortars have been designed with different substitution rates of biomass fly ashes from wood combustion in thermal power plant. Although there is an overall decrease in performance, mortars made with biomass ash retain properties that make them suitable for use in masonry or rendering.

Egg white lysozyme was modified by chemical methods using organic acids. Caffeic acid and p-coumaric acid in organic acids were used as modifiers, and 1-Ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxy succinimide were used as dehydration condensation agents during modification. A certain degree of modified lysozyme was obtained through appropriate modification conditions. The antibacterial properties and structure of the obtained two organic acid modified lysozymes were compared with natural enzymes. The results showed that compared with the natural enzyme, the activity of modified lysozyme decreased, but the inhibitory effect on Gram-negative bacteria was enhanced. The minimum inhibitory concentrations of caffeic acid modified enzyme and p-coumaric acid modified enzyme on Escherichia coli and Pseudomonas aeruginosa were 0.5 mg/mL and 0.75 mg/mL, respectively. However, the antibacterial ability of modified lysozyme to Gram-positive bacteria was lower than that of natural enzyme. The minimum inhibitory concentration of caffeic acid modified enzyme and p-coumaric acid modified enzyme to Staphylococcus aureus and Bacillus subtilis was 1.25 mg/mL. The peak fitting results of the amide-I band (1600 cm-1-1700 cm-1) absorption peak in the infrared spectroscopy showed that the content of the secondary structure of the two modified enzymes obtained after modification was different from that of natural enzymes.

As precision medicine such as targeted therapy and immunotherapy often have limited accessibility, low response rate and evolved resistance, it is urgent to develop simple, low-cost, and quick-turnaround personalized diagnostic technologies for drug response prediction with high sensitivity, speed, and accuracy. Major challenges of drug response prediction strategies employing digital database modeling are the scarcity of labeled clinical data, applicable only to a few classes of drugs, and losing the resolution at the individual patient level. Although these challenges have been partially addressed by large-scale cancer cell line datasets and more patient-relevant cell-based systems, the integration of different data types and data translation from pre-clinical to clinical utilities are still far-fetched. To overcome current limitations of precision medicine with a clinically proven drug response prediction assay, we have developed an innovative and proprietary technology based on in vitro patient testing and in silico data analytics. First, a patient-derived gene expression signature was established via transcriptomic profiling of cell-free mRNA (cfmRNA) from the patient’s blood. Second, a gene-to-drug data fusion and overlaying mechanism to transfer data was performed. Finally, a semi-supervised method was used for database searching, matching, annotation and ranking of drug efficacies from a pool of ~700 approved, investigational or clinical trial drug candidates. A personalized drug response report can be delivered to inform clinical decision within a week. The PGA (Patient-derived Gene expression-informed Anticancer drug efficacy) test has significantly improved patient outcomes when compared to the treatment plans without PGA support. Implementation of PGA, which combines patient-unique cfmRNA fingerprints with drug mapping power, has the potential to identify treatment options when patients are no longer responding to therapy and when standard-of-care is exhausted.