bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of CRISPR/Cas9 Gene Editing System in Sheep Oocytes via Microinjection
Authors: Wang Haitao , Yang Hengqian , Li Tingting , Chen Yan , Chen Jieran , Zhang Xiaosheng , Zhang Jinlong , Zhang Yuting , Zhang Na , Ma Runlin , Huang Xun , Liu Qiuyue
Published: December 2024

The CRISPR/Cas9 system has become a powerful tool for molecular design breeding in livestock such as sheep. However, the efficiency of the Cas9 system combined with zygote microinjection remains suboptimal. In this study, mature sheep oocytes were used for microinjection to assess the impact of various factors on Cas9 editing efficiency. We found that the in vitro maturation efficiency of oocytes is influenced by environmental factors such as air temperature, pressure, and humidity. Our results indicate that high-efficiency gene editing can be achieved when targeting the SOCS2, DYA, and TBXT genes, using a microinjection mixture with a concentration of 10 ng/μl Cas9 and sgRNA. By optimizing the injection capillary, we significantly reduced the oocyte invalidation rate post-microinjection to 3.1–5.3%. Furthermore, we observed that using either Cas9 protein or mRNA in the microinjection process resulted in different genotypes in the edited oocytes. Importantly, parthenogenetic activation did not appear to affect the editing efficiency. Using this high-efficiency system, we successfully generated SOCS2 or DYA gene-edited sheep, with all lambs confirmed to be genetically modified. This study presents a highly efficient method for producing gene-edited sheep, potentially enabling more precise and effective strategies for livestock breeding.
Metformin in Antiviral Therapy: Evidence and Perspectives
Authors: Halabitska Iryna , Petakh Pavlo , Lushchak Oleh , Kamyshna Iryna , Oksenych Valentyn , Kamyshnyi Oleksandr
Published: December 2024

Metformin, a widely used antidiabetic medication, has emerged as a promising broad-spectrum antiviral agent due to its ability to modulate cellular pathways essential for viral replication. By activating AMPK, metformin depletes cellular energy reserves that viruses rely on, effectively limiting the replication of pathogens such as Influenza, HIV, SARS-CoV-2, HBV, and HCV. Its role in inhibiting the mTOR pathway, crucial for viral protein synthesis and reactivation, is particularly significant in managing infections caused by HIV, CMV, and EBV. Furthermore, metformin reduces oxidative stress and reactive oxygen species (ROS), which are critical for replicating arboviruses such as Zika and dengue. The drug also regulates immune responses, cellular differentiation, and inflammation, disrupting the life cycle of HPV and potentially other viruses. These diverse mechanisms suppress viral replication, enhance immune system functionality, and contribute to better clinical outcomes. This multifaceted approach highlights metformin's potential as an adjunctive therapy in treating a wide range of viral infections.
Improving the Accuracy of Bone-scintigraphy Imaging Analysis Using the Skeletal Count Index: A Study Based on Human Trial Data
Authors: Miki Ryosuke , Tsuchitani Tatsuya , Takahashi Yoshiyuki , Kitajima Kazuhiro , Takahashi Yasuyuki
Published: December 2024

The image quality index for whole-body bone scintigraphy has traditionally relied on the total count (Total-C) with a threshold of ≥1.5 mc. However, Total-C measurements are susceptible to variability owing to urine retention. This study aimed to develop a skeletal count (Skel-C)-based index, focusing exclusively on bone regions, to improve the accuracy of image analysis in bone scintigraphy. All cases included herein were Total-C≥1.5 mc. Thresholds were set for Skel-C (0.9–1.2 mc) and Total-C (1.75–2.25 mc); patients were grouped according to whether they were above or below these thresholds. The group including all cases was defined as the Total-C 1.5 high group. Sensitivity and specificity were calculated for each group, and receiver operating characteristic analyses and statistical evaluations were conducted. The specificity of the Skel-C < 0.9 mc group was significantly lower than that of the Skel-C ≥ 0.9 mc group and the Total-C 1.5 high group. These findings highlight the importance of achieving Skel-C ≥ 0.9 mc and suggest that Total-C alone is insufficient for reliable image assessment.
The Lasting Consequence of Bernstein’s Theoretical Error
Authors: Delalande Bernard , Tamagawa Hirohisa , Matveev Vladimir
Published: December 2024

Julius Bernstein developed a membrane theory based on potassium diffusion and the Nernst equation, which is considered fundamental in electrochemistry. This foundational equation has been adapted for applications in biophysics and biology through the widely recognized Goldman Hodgkin Katz equation. The Nernst equation is one of the most frequently utilized equations in biology. However, a thorough comparison of their applications reveals significant similarities as well as substantial, at times irreconcilable, differences. These differences question the validity of the biological "version" of the equation, since its distinct features diverge markedly from the original Nernst equation, to the extent that the biological adaptation introduces concepts that are incompatible with current scientific understanding in the fields of thermodynamics and physics.
Highly Efficient Polarization-Insensitive Grating Couplers on Thin-Film Lithium Niobate with an Integrated Gold Layer
Authors: Sulan Alaa , Khalil Mostafa , Mehravar Leila , Xu Chang-qing
Published: December 2024

The thin-film lithium niobate platform, which is emerging as a promising photonic integration platform, currently lacks a polarization-insensitive grating coupler (GC), a crucial component for polarization-independent fiber interfaces. This limitation restricts its use in many applications such as polarization-insensitive modulation systems and polarization management. In this study, we propose a polarization-insensitive nonuniform GC, achieved by intersecting optimal TE- and TM-mode grating periods. Based on our simulation results, the proposed design delivers a coupling efficiency (CE) of 80% for TE and 78.5% for TM polarization, with a polarization-dependent loss of less than 0.14 dB at a wavelength of 1550 nm. The inserted gold layer, i.e., inside the substrate layer, boosts the CEs of the optimal TE- and TM-mode GC by about 50%, resulting in a highly efficient, polarization-insensitive solution. This advancement enables on-chip polarization diversity applications on the thin-film lithium niobate platform. We also investigate the fabrication and alignment tolerances of the proposed design to ensure robust performance under practical conditions.
Impact of Silver and Silver-Based Alloys on Human Health. An In Vitro Assessment of Dental Applications
Authors: Reclaru Lucien , Forna Norina Consuela , Forna-Agop Doriana , Pantea Mihaela
Published: December 2024

(1) Background: Silver and silver-based alloys are not mutagenic, carcinogenic or toxic to reproduction. However, the European Chemicals Agency (ECHA) has decided to include ionic silver and silver nanoparticles in the list of biocidal substances. In this context, we aimed to evaluate the quantities of silver released and the cytotoxicity of silver-based dental alloys sourced from two distinct suppliers present in the EU (European Union) markets. (2) Methods: Five dental alloys, with silver contents ranging from 9.2% to 58%, were tested by extraction tests in a solution of racemic lactic acid and sodium chloride (7-day extraction at 37°C). The cytotoxic behavior of five other dental alloys with silver contents ranging from 22.4% to 59% was evaluated, as well. (3) Results: Extraction test results indicate small quantities of silver, ranging from 55μg/L to 243μg/L. The assessment of alloys’ cytotoxicity reveals variability of the obtained results; however, none of the tested alloys can be considered cytotoxic. (4) Conclusions: The obtained results indicate that the silver-based alloys included in this study do not pose a risk when used in the oral cavity.
Reduction of Acute Bee Paralysis Virus Infection and Mortality in Honeybees (Apis mellifera) by RNA Interference Technology
Authors: Ferrufino Cecilia , Scannapieco Alejandra Carla , Russo Romina Maria , Gonzalez Fernanda Noemí , Salvador Ricardo , Dus Santos María José
Published: December 2024

In Argentina, various studies have reported the detection of multiple viruses in honey-producing and queen-rearing apiaries, with Aparavirus apisacutum, the causal agent of acute bee paralysis (ABP), demonstrating a particularly high prevalence. The potential of RNA interference (RNAi) as a strategy to control honeybee viruses has been explored, with initial findings indicating that RNAi could aid in mitigating the economic losses associated with viral infections. This study aimed to evaluate the effect of RNAi technology mediated by double-stranded RNA (dsRNA) on the dynamics of ABPV infection in adult honeybees. Fragments of the ABPV replicase and VP1 genes were used as templates for dsRNA synthesis via in-vitro transcription. A gene silencing experiment was conducted through oral administration using five treatments: control, specific dsRNA + Virus, Virus alone, specific dsRNA alone, and non-specific dsRNA + virus. Bee survival was recorded over 10 days for all treatments, and samples were subsequently processed for viral quantification using quantitative real-time PCR. The oral administration of specific dsRNA reduced the viral replication curve, decreased the average viral loads and increased bee survival. This is the first report demonstrating the reduction of ABPV infection in adult honeybees through post-transcriptional gene silencing achieved via oral administration of dsRNA.
Mechanism of the Ikaite Formation in the Modern Sediments of the Kara Sea
Authors: Krylov Alexey A. , Logvina Elizaveta Aleksandrovna , Gusev Evgeny A. , Yarzhembovsky Yaroslav , Krzhizhanovskaya Maria Georgievna , Zykov Evgeny , Zengzhao Yu , Urvantsev Dmitry , Dubenskiy Alexander S , Okina Olga I.
Published: December 2024

The article discusses possible mechanisms for the formation of ikaite (CaCO3·6H2O) in the sediments of the Kara Sea. We combined our own data with the results of previous studies on calcium carbonate hexahydrates in this region. X-ray diffraction analysis of ikaite revealed its transformation into calcite, providing valuable insight into its mineralogical evolution. Stable isotope analyses suggest that the main process leading to ikaite formation is microbial degradation of organic matter through sulfate reduction, which increases the concentration of dissolved inorganic carbon and phosphate ions in the pore water. Carbon that enters the bicarbonate ion as a result of anaerobic oxidation of methane (AOM) can also contribute to the formation of ikaite in some cases. However, AOM alone does not lead to the release of magnesium or phosphate ions, which are known to inhibit calcite precipitation. Consequently, without the simultaneous microbial decomposition of organic matter or the presence of unstable magnesium-rich minerals, AOM alone is not sufficient for ikaite formation. Our sample analyses show that the proportion of methane-derived carbon in ikaite does not exceed 62%, while the contribution of organic carbon can be as high as 100%. Furthermore, rare earth element (REE) analysis supports the significant role of diagenetic organic matter degradation in sediments where ikaite is present. These findings highlight the complex relationship between the decomposition of organic matter, the oxidation of methane, and the formation of ikaite in the early diagenetic sediments of the Kara Sea.
A 2-for-1 Diagnosis: A Rare Case of Chronic Abdominal Pain Caused by Gastroptosis and Wilkie’s Syndrome in a Young Woman
Authors: Youssoufi Nosseir , Jaafari Ayoub , Mansour Sohaïb , El Hamdi Mohamed , Gallerani Andrea , Pierrakos Charalampos , Attou Rachid
Published: December 2024

Long-term abdominal pain (LAP) affects 30% to 40% of children on a weekly basis, representing a signifi-cant challenge for medical practitioners due to the extensive differential diagnoses and often-inconclusive work-up. It often results from functional gastrointestinal disorders (FGIDs) such as functional dyspepsia (postprandial distress syndrome, epigastric pain syndrome) and irritable bowel syndrome (IBS), but can also be associated with inflammatory bowel disease (IBD), allergic bowel disease (ABD) and psychological fac-tors. However, less common causes include visceroptosis, specifically gastroptosis, and superior mesenteric artery (SMA) syndrome. Visceroptosis, or Glenard's disease, involves the downward displacement of visceral organs due to ligament laxity, while gastroptosis refers to the specific downward displacement of the stomach. SMA (Wilkie syndrome) is a rare condition in which the third part of the duodenum is compressed between the abdominal aorta and the superior mesenteric artery. Both conditions were first described in the 19th century and are more common in young women. While a few cases of these conditions separately have been reported in the literature, no cases have documented their simultaneous coexistence. Here we present the case of a 17-year-old girl with a six- to seven-month history of postprandial abdominal pain and vomiting who was di-agnosed with both gastroptosis and SMA. We also provide a comprehensive literature review.
Retrospective Clinical Investigation Into the Association Between Abnormal Blood Clotting, Oral Anticoagulant Therapy and Medium-Term Mortality in a Cohort of COVID 19 Patients
Authors: Dinoi Giorgia , Togo Maria Vittoria , Guida Pietro , Deruvo Caterina , Samarelli Francesco , Imbrici Paola , Nicolotti Orazio , De Luca Annamaria , Mastroianni Franco , Liantonio Antonella , Altomare Cosimo Damiano
Published: December 2024

People affected by COVID-19 are exposed to abnormal clotting and endothelial dysfunction which may trigger thromboembolic events. This study aimed at retrospectively investigating whether the oral anticoagulant therapy (OAT), encompassing either direct oral anticoagulants (DOACs), mainly apixaban, or the vitamin K antagonist (VKA) warfarin, may impact on the medium-term mortality in a large cohort of SARS-CoV-2 patients. Among 1238 COVID-19 patients, hospitalized from March 17, 2020, to June 15, 2021, 247 survivors and 247 deceased within 90 days from hospitalization were matched 1:1 based on age, sex and Intensive Care Unit (ICU) admission within three days. Conditional logistic regression was used to estimate associations by means of Odds Ratio (OR) with 95% confidence interval. Compared to patients living at 90 days, those who suffer a fatal event achieved more frequently heart failure, HF (10.5% vs 23.1%; p < 0.001), atrial fibrillation, AF (13.4% vs 22.3%; p = 0.009), as well as respiratory disease or chronic obstructive pulmonary disease (COPD), and renal failure. While HF and AF emerged as the comorbidities mainly associated to medium-term mortality of COVID-19, patients in OAT, no differently from those treated with subcutaneous low-molecular weight heparins (LMWHs) during hospitalization, did not show any significant impact on mortality. In contrast, quite surprisingly, the use of canrenone as mineralcorticoid receptor antagonist in antihypertensive therapy, appeared to worsen the clinical course of COVID-19 patients, whereas vitamin D supplementation showed beneficial effects. The use of a digital predictive platform (PLATO, Polypharmacology pLATform predictiOn) and search into the Eudravigilance database suggested potential associated off-target drug activities, such as modulation of A3 adenosine receptor, and to postulate how aldosterone antagonists might contribute to increase severity of SARS-CoV-2 infection.
Personalized Occlusal Scheme: Occlusion and Biomechanical Risk Factors in Implant-Supported Complete Fixed Dentures. Narrative Review
Authors: Berzaghi Andrea , Testori Tiziano , Scaini Riccardo , Bortolini Sergio
Published: December 2024

The biophysiological differences between teeth and dental implants and the issue of occlusal overload, although controversial, form the basis for the management of occlusion in im-plant-supported fixed complete dental prostheses (IFCDPs). Although occlusion management is currently lacking in scientific evidence, it is nevertheless evident that the favorable prognosis of IFCDPs is linked to a correct understanding of the biomechanical principles involved. In the de-sign of IFCDPs, the lack of proprioceptive feedback requires special attention to biomechanical factors: minimizing overload complications and conferring biomechanical stability are among the main goals of occlusion. In IFCDPs, the occlusion has to be decided on the basis of several factors affecting the loads on prosthesis and implants: each case has to be evaluated individually and needs a customized occlusion. The main goal of this narrative review is to provide an overview of the occlusal principles and materials that can be used in IFCDPs based on the data currently available in the literature. The research proposes practical clinical recommendations for the oc-clusion management of IFCDPs and a biomechanical risk score index aimed at customizing im-plant-prosthetic treatment.
Understanding Patterns of the Gut Microbiome May Contribute to an Early Detection and Prevention of Type 2 Diabetes Mellitus
Authors: Bednarska Natalia G , Håberg Asta Kristine
Published: December 2024

The rising burden of type 2 diabetes mellitus (T2DM) is a growing global public health problem, particularly prominent in developing countries. Early detection of T2DM and prediabetes is vital for reversing the outcome of disease, allowing early intervention. In the past decade various mi-crobiome-metabolome studies attempted to address the question whether there are any common microbial patterns which would indicate either prediabetic or diabetic gut microbial signatures. Because current studies have a high methodological heterogeneity and risk of bias, we have se-lected studies which adhered to similar design and methodology. We have performed a system-atic review to assess if there are any common changes in microbiome belonging to diabetic, pre-diabetic and healthy individuals. The presented here cross-sectional studies collectively covered a population of 65754 people, with 1800 in 2TD group, 2770 in prediabetic group and 61184 in control group. The overall microbial diversity scores were lower in T2D and prediabetes cohort in 86% of analysed herein studies. Re-programming microbiome is potentially one of the safest and long-lasting ways to eliminate diabetes in its early stages. The differences in abundance of certain microbial species could serve as an early warning for a dysbiotic gut environment and could be easily modified before the onset of disease by changes in lifestyle, through taking probi-otics, introducing diet modifications, or stimulating vagal nerve. This review shows how meta-genomic studies already had and will continue uncovering novel therapeutic targets (probiotics, prebiotics or targets for elimination from flora). This work clearly shows that gut microbiome intervention studies, if performed according to standard operating protocols using predefined analytic framework (e.g. STORMS), could be combined with other similar studies allowing broader conclusions from collating all global cohort studies efforts and eliminating the effect-size statistical insufficiency of a single study.
Noncanonical Third-Order Advanced Differential Equations of Unstable Type: Oscillation and Property B via Canonical Transform
Authors: Rani B. , Chatzarakis George , Thandapani E.
Published: December 2024

In this paper, we obtain sufficient conditions for the third-order nonlinear advanced differential equation (a₂(t)(a₁(t)y′(t))′)^{′α}(σ(t)) with ∫_{t₀}^{∞}(1/(a₂(t)))dtwith $$\int_{t_0}^{\infty}\frac{1}{a_2(t)}dt<\infty\;\text{and}\;\int_{t_0}^{\infty}\frac{1}{a_1(t)}dt<\infty,$$ to have property B or to be oscillatory. This is achieved by transforming the studied equation into canonical type and then using integral averaging method. Examples are provided to illustrate the main results.
Line Spreads That Produce Projective Planes
Authors: Van Maldeghem Hendrik
Published: December 2024

We classify in an explicit way those line spreads of projective 5-space over a field that have the property that the given spread induces a spread in the 3-space generated by any pair of spread lines. We determine their fix groups and conclude that there exist such spreads with trivial fix group. Also, we characterise regular line spreads among all line spreads of projective 3-space by their projectivity group, and also by a weakening of the regularity condition.
The Effect of Geometrical Shape of Surface Texture on Rheology and Tribology of Confined Lubricants
Authors: Peng Fankai , Jabbarzadeh Ahmad
Published: December 2024

Understanding lubrication at the nanoscale is essential for reducing friction. While alkanes, the primary component in most lubricants, have been extensively studied for their molecular structure's impact on rheology and behaviour when confined by solid surfaces, the influence of confining surface texture remains underexplored. This research uses molecular dynamics simulations to investigate the rheological behaviour of thin film lubrication between various patterned rough surfaces. The study focuses on three types of wave-patterned surfaces: sinusoidal, sawtooth, and squaretooth. Hexadecane, a linear alkane, is used as the lubricant. The simulations examine the effects under different normal loads and shear rates. Surface patterns significantly influence the formation and structure of crystalline bridges. This, however, depends on shear rates and normal loads. Under low normal load and shear rate conditions, the sawtooth wave-patterned surface exhibits the highest viscosity by forming crystalline bridges with molecular orientation perpendicular to the shear direction. The squaretooth patterns exhibit the lowest viscosities due to the nematic order in crystalline bridges with molecules aligned in the shearing direction. The lubricant viscosity with a sinusoidal wave-patterned surface is an intermediary with disordered crystalline bridge groups formed with random molecular orientation. The lowest viscosity provided by the squaretooth pattern surface persists for the transitory state as well as the steady state on both high and low loads and over a wide band of shear rates. However, the extent of the difference in shear viscosity is reduced at higher normal loads. This research provides valuable insights for designing nanoelectromechanical systems (NEMS) and other applications where boundary conditions are critical to lubrication.
Changes in the Responses of Leaf Gas Exchange to Temperature and Photosynthesis Model Parameters After a Few Days of Contrasting Temperatures in Four C3 Species in the Field
Authors: Bunce James
Published: December 2024

Substantial variation in the temperature dependence of parameters of the Farquhar, von Caemmerer, and Berry C3 photosynthesis model, as well as of in vitro Rubisco kinetic characteristics have been observed in controlled conditions, but have seldom been systematically examined in the field. In this work, A vs. Ci curves were measured over a 15 or 20 oC range of temperatures in four C3 species growing outdoors, on two occasions about three weeks apart during one growing season. The two occasions were chosen for having contrasting temperatures for 3 to 4 days preceding the measurements. Low temperatures (mean maximum/minimum temperatures of 19/11 oC) resulted in higher values of the VCmax of Rubisco and Jmax at a given measurement temperature in most species compared with higher temperatures (max/min 31/25 oC). The apparent activation energy of VCmax of Rubisco ranged from 56 to 82 kJ mol-1, and that of electron transport (Jmax) ranged from 28 to 56 kJ mol-1 across species and prior temperatures. In three of the four species the activation energy of VCmax decreased and that of Jmax increased after the cooler temperatures. Stomatal conductance measured at 20 and 25 oC increased strongly with the prior warm temperatures in all species. Photosynthesis at air levels of CO2 was substantially decreased by the prior warmer temperatures in one species, but little changed in the three other species.
Probing Constitutive Traits of Metabolic Adaptation in Cyanobacteria to Extreme Habitats
Authors: Bilova Tatiana , Golushko Nikita , Frolova Nadezhda , Soboleva Alena , Silinskaya Svetlana , Khakulova Anna , Orlova Anastasia , Sinetova Maria , Los Dmitry , Frolov Andrej
Published: December 2024

Cyanobacteria isolated from extreme habitats are promising in biotechnology due to their high adaptability to unfavorable environments and their specific natural products. Therefore, these organisms are stored under reduced light supply in multiple collections worldwide. However, it remains unclear whether these strains retain the primary metabolome features associated with their unique adaptations. To address this question, a comparative analysis of primary metabolomes of twelve cyanobacterial strains from diverse extreme habitats was performed by combined GC-MS/LC-MS approach. The results revealed that all these cyanobacterial strains exhibited clear differences in their patterns of primary metabolites. These metabolic differences were more pronounced for the strains originating from ecologically different extreme environments. Extremotolerant terrestrial and freshwater strains contained lower strain-specifically accumulated primary metabolites than extremophilic species from the habitats with high salinity and alkalinity. The latter group of strains was highly diverse in amounts of specific primary metabolites. This might indicate essentially different molecular mechanisms and metabolic pathways behind the survival of the microorganisms in saline and alkaline environments. The identified strain-specific metabolites are discussed with respect of the metabolic processes that might impact on maintaining the viability of cyanobacteria during their storage and indicate unique adaptations formed in their original extreme habitats.
Cardioprotective Activity of the Ethanolic Leaf Extract of Amaranthus viridis on Verapamil-Induced Heart Failure in Zebrafish (Danio rerio)
Authors: Rodriguez Leonel Paolo S. , Abalos Norielyn N.
Published: December 2024

Cardiovascular disease (CVD), a major global health concern, is characterized by cardiac complications that can lead to death. The commonly used treatments for this condition are synthetic drugs, but these often come with risky side effects. A potential alternative is the use of traditional medicinal plants, such as Amaranthus viridis, which is rich in bioactive compounds. This study aimed to determine the non-toxic concentration of A. viridis ethanolic extract, investigate its cardioprotective effects on zebrafish (Danio rerio) heart rate and cardiac phenotype, qualitatively assess the presence of phytochemicals, and assess its antioxidant activity using DPPH free radical scavenging activity. Zebrafish larvae at 72 hours post-fertilization (hpf) were used to evaluate mortality and optimize dosing. Physio-morphological screening was conducted by pre-treating zebrafish larvae with the extract 4 hours prior to administering a heart failure inducer, verapamil. The maximum non-toxic concentration was found to be 25 µg/mL, as all zebrafish survived after 24 hours. Mortality began at 50 µg/mL, and concentrations from 100 µg/mL to 400 µg/mL resulted in 100% mortality. All tested concentrations of A. viridis leaf extract showed cardioprotective activity in the physio-morphological analysis, with 3.125 µg/mL identified as the lowest effective dose. Phytochemical analysis detected the presence of alkaloids and phenols. Furthermore, A. viridis exhibited antioxidant activity from all tested concentrations. Based on the results, A. viridis exhibited cardioprotective effects against verapamil-induced cardiotoxicity, as evidenced by the recovery of heart rate and cardiac phenotype in the zebrafish model.
DNA vaccine encoding a modified hemagglutinin of influenza A/H5N8 virus protects mice from infection with a lethal dose of influenza A/H5N1 virus
Authors: Rudometov Andrey P. , Litvinova Victoria R. , Gudymo Andrei S. , Ivanova Ksenia I. , Rudometova Nadezhda B. , Kisakov Denis N. , Borgoyakova Mariya B. , Kisakova Lyubov A. , Yakovlev Vladimir A. , Tigeeva Elena V. , Vahitov Danil I. , Makarova Kristina P. , Kolosova Natalia P. , Ilyicheva Tatiana N. , Marchenko Vasiliy Yu. , Sergeev Artemiy A. , Karpenko Larisa I. , Ilyichev Alexander A.
Published: December 2024

Highly pathogenic avian influenza (HPAI) H5 clade 2.3.4.4b viruses are widespread in wild and domestic birds, causing severe economic damage to the global poultry industry. Moreover, viruses of this clade can adapt to mammals, posing a potential pandemic threat. With the constant evolution and change of dominant strains of H5 clade 2.3.4.4b, it is important to investigate the cross-reactivity of available and developing vaccine preparations. In this study, the immuno-genicity of the previously developed DNA vaccine encoding a modified hemagglutinin of influ-enza A/turkey/Stavropol/320-01/2020 (H5N8) virus, administered by jet injection at doses of 1, 10, 50, 100 and 200 μg, was investigated. The highest titer of specific to recombinant hemagglutinin antibodies was detected in the group of animals injected with 100 µg of DNA vaccine. The cross-reactivity study of sera of animals immunized with 100 µg of DNA vaccine in microneutralization assay against strains A/chicken/Astrakhan/321-05/2020 (H5N8), A/chicken/Komi/24-4V/2023 (H5N1), A/chicken/Khabarovsk/24-1V/2022 (H5N1) and A/chicken/Voronezh/193-1V/2024 (H5N1) showed the formation of cross-neutralizing antibodies. Moreover, the study of protective properties showed that the DNA vaccine prevented morbidity and mortality of animals after infection with both homologous strain A/Astrakhan/3212/2020 (H5N8) and heterologous strain A/chicken/Khabarovsk/24-1V/2022 (H5N1).
Fish Larval Assemblage Associated to an Eastern Tropical Pacific Coral Reef: Seasonal and Interannual Variability
Authors: Gallego-Zerato Juan José , Córdoba-Rojas Diego Fernando , Giraldo Alan
Published: December 2024

The seasonal and interannual temporal variation of the structure, richness, diversity and similarity of fish larval assemblages associated to an Eastern Tropical Pacific coral reef system, was assessed for the period 2017 to 2019. A total of 4779 fish larvae were captured, of which 4556 (95% of the total) were identified, belonging to 88 species and 46 families, and increasing the number of larvae of fish species reported to 162 taxa. Based on the analysis of similarity between oceanographic seasons and between years, six significant groups were established (SIMPROF, p < 0.05), each group made up of the nine sampling stations belonging to each study period (ANOSIM, R = 0.764). C. mysticetus, D. pacificus, Anchoa sp., Anisotremus sp., B. bathymaster, O. saurus, Caranx sp., Seriola sp., Gobiidae sp., Microgobius sp., and S. evermanni were the species that contributed to the differentiation of the groups. Species richness distribution during the sampling periods was variable and did not show a clear temporal or annual trend. However, the fish larvae assamblages were ordered according with the cold and warm seasons, suggesting that intra-annual variation has a strong influence on the temporal dynamics of fish larval assemblages in ETP coral reef systems.
Synthesis of New Polyfluoro Oligonucleotides via Staudinger Reaction
Authors: Klabenkova Kristina , Zakhryamina Alyona , Burakova Ekaterina , Bizyaev Sergei , Fokina Alesya , Stetsenko Dmitry
Published: December 2024

Nowadays, nucleic acid derivatives capable of modulating gene expression at the RNA level gained widespread recognition as promising therapeutic agents. A suitable degree of biological stability of oligonucleotide therapeutics that is required for in vivo application can be most expeditiously achieved by chemical modification of the internucleotidic phosphate group, which may also affect their cellular uptake, tissue distribution and pharmacokinetics. Our group has previ-ously developed a strategy for the chemical modification of the phosphate group via Staudinger reaction on solid phase of the intermediate dinucleoside phosphite triester and a range of, pref-erably, electron deficient organic azides such as sulfonyl azides during automated solid-phase DNA synthesis according to the conventional β-cyanoethyl phosphoramidite scheme. Polyfluoro compounds are characterized by unique properties that prompted their extensive application both in industry and in scientific research. We report herein the synthesis and isolation of novel oligodeoxyribonucleotides incorporating internucleotidic perfluoro-1-octanesulfonyl phospho-ramidate or 2,2,2-trifluoroethanesulfonyl phosphoramidate groups. In addition, novel oligonu-cleotide derivatives with fluorinated zwitterionic phosphate mimics were synthesized by a tan-dem methodology, which involved: (a) introduction of a carboxylic ester group at the internu-cleotidic position via a Staudinger reaction with methyl 2,2-difluoro-3-azidosulfonylacetate; and (b) treatment with an aliphatic diamine, e.g. 1,1-dimethylethylenediamine or 1,3-diaminopropane. It was further shown that the polyfluoro oligonucleotides obtained were able to form comple-mentary duplexes with either DNA or RNA, which were not significantly differing in stability from the natural counterparts. Long-chain perfluoroalkyl oligonucleotides were taken up into cultured human cells in the absence of a transfection agent. It may be concluded that the polyfluoro oligonucleotides described here can represent a useful platform for designing oligonucleotide therapeutics.
Median Based Unit Weibull Distribution (MBUW): Does the Higher Order Probability Weighted Moments (PWM) Add More Information over the Lower Order PWM in Parameter Estimation
Authors: Attia Iman
Published: December 2024

In the present paper, Probability weighted moments (PWMs) method for parameter estimation of the median based unit weibull (MBUW) distribution is discussed. The most widely used first order PWMs is compared with the higher order PWMs for parameter estimation of (MBUW) distribution. Asymptotic distribution of this PWM estimator is derived. This comparison is illustrated using real data analysis.
Integrative Genomic and Cytogenetic Analyses Reveal the Landscape of Typical Tandem Repeats in Water Hyacinth
Authors: Feng Liqing , Huang Yongji , Zhong Cairong , Fang Jingping , Tian Dagang
Published: December 2024

In eukaryotes, tandem repeats are often unstable, leading to rapid evolutionary changes. However, the evolutionary dynamics of these repeats in allopolyploids like the water hyacinth remain (Eichhornia crassipes or Pontederia crassipes) poorly understood. In our study, we analyzed five typ-ical tandem repeats in the allotetraploid water hyacinth using genomic and cytogenetic methods. We found non-random distribution and copy number variation across the genome. The highly abundant centromeric tandem repeat, putative CentEc, co-localized with the centromeric re-trotransposon CREc, indicating conserved centromeric features. Putative CentEc sequences showed high conservation (91%-100%), suggesting ongoing concerted evolution post-subgenome divergence. Fluorescence in situ hybridization (FISH) analysis showed telomere sequences on all chromosomes, with tandem repeat of interstitial chromosome regions (ICREc) only on certain chromosomes, both exhibiting copy number variation. Moreover, 5S rDNA was detected on one chromosome pair, and 35S rDNA on multiple chromosomes with varying intensities. Examination of the genome assembly also revealed sequence heterogeneity in copies of 5S and 35S rDNA from the two subgenomes, implying divergent evolution of these two rDNA families within their re-spective subgenomes. Our findings highlight the role of tandem repeats in the water hyacinth genome's structure and evolution, with implications for understanding the genomic dynamics of invasive species.
Dual Roles of miR-10a and miR-10b as Tumor Suppressors and Oncogenes in Diverse Cancers
Authors: Singh Rajan , Ha Se Eun , Yu Tae Yang , Ro Seungil
Published: December 2024

Cancer is a complex genetic disorder characterized by abnormalities in both coding and regulatory non-coding RNAs. microRNAs (miRNAs) are key regulatory non-coding RNAs that modulate cancer development, functioning as both tumor suppressors and oncogenes. miRNAs play critical roles in cancer progression, influencing key processes such as initiation, promotion, and metastasis. They exert their effects by targeting tumor suppressor genes, thereby facilitating cancer progression, while also inhibiting oncogenes to prevent further disease advancement. The miR-10 family, particularly miR-10a and miR-10b (miR-10a/b), is notably involved in cancer progression. Intriguingly, their functions can differ across different cancers, sometimes promoting and at other times suppressing tumor growth depending on the cancer type and molecular environment. This review explores the dual roles of miR-10a/b as tumor suppressor miRNAs (TSmiRs) or oncogenic miRNAs (oncomiRs) in various cancers by examining their molecular and cellular mechanisms and their impact on the tumor microenvironment. Furthermore, we discuss the potential of miR-10a/b as therapeutic targets, emphasizing miRNA-based strategies for cancer treatment. Insights discussed in this review aim to advance our understanding of miR-10a/b's roles in tumor biology and their application in developing innovative cancer therapies.
Prevalence of Mpox Vaccine Acceptance Among Students: A Systematic Review and Meta-Analysis
Authors: Yappalparvia Ambanna , Gaidhane Shilpa , Padmapriya G. , Kaur Irwanjot , Lal Madan , Iqbal Suhaib , Prasad G. V. Siva , Pramanik Atreyi , Sharma Promila , Malik Praveen , Vishwakarma Teena , Punia Ankit , Jagga Megha , Mehta Rachana , Sah Sanjit , Shabil Muhammed , Satapathy Prakasini , Bushi Ganesh , Parsa Ali Davod , Kabir Russell
Published: December 2024

Background: Mpox, formerly known as monkeypox, is a re-emerging viral disease. Vaccine acceptance is crucial for preventing its spread. This systematic review and meta-analysis assessed the acceptance of the Mpox vaccine among student populations. Methods: We searched electronic databases including PubMed, Web of Science, and Embase up to September 14, 2024. The studies included were observational, such as cross-sectional and cohort studies, and specifically assessed vaccine acceptance for Mpox vaccines among students. R version 4.4 was used to perform meta-analysis and sensitivity analyses were conducted to assess the robustness of the findings. Publication bias was evaluated using Doi plots. Results: Of the 143 studies initially identified, eight studies were included in the final analysis, comprising a total of 16,129 participants. The overall vaccine acceptance rate was 58.6%, with considerable variability across studies (I² = 100%). Sensitivity analyses indicated that acceptance rates ranged between 45% and 70%. The Doi plot demonstrated the presence of moderate publication bias. Conclusion: This systematic review and meta-analysis show moderate acceptance of the Mpox vaccine among students. Future studies should investigate the factors influencing vaccine acceptance and design targeted strategies to improve coverage, which will be essential for controlling Mpox and ensuring successful vaccination campaigns.
Responsivity of Two Pea Genotypes to the Symbiosis with Rhizobia and Arbuscular Mycorrhiza Fungi – a Proteomics Aspect of the “Efficiency of Interactions with Beneficial Soil Microoganisms” Trait
Authors: Frolov Andrej , Shumilina Julia , Etemadi Afshar Sarah , Mashkina Valeria , Rhomanovskaya Ekaterina , Lukasheva Elena , Tsarev Alexander , Sulima Anton S. , Shtark Oksana , Ihling Christian , Soboleva Alena , Tikhonovich Igor A. , Zhukov Vladimir. A
Published: December 2024

It is well-known that individual pea (Pisum sativum L.) cultivars differ in their symbiotic responsivity. This trait is typically manifested with an increase in seed weights due to inoculation with rhizobial bacteria and arbuscular mycorrhizal fungi. The aim of this work was to characterize the alterations in root proteome of highly responsive pea genotype k-8274 and low-responsive genotype k-3358 grown in non-sterile soil, which were associated with root colonization with rhizobial bacteria and arbuscular mycorrhiza fungi in comparison to proteome shifts caused by soil supplementation with mineral nitrogen salts. Our results clearly indicate that supplementation of the soil with mineral nitrogen-containing salts switched the root proteome of both genotypes to assimilation of the available nitrogen, whereas the processes associated with nitrogen fixation were suppressed. Surprisingly, inoculation with rhizobial bacteria had only a minor effect on root proteomes of the both genotypes. The most pronounced response was observed for highly responsive k-8274 genotype inoculated simultaneously with rhizobial bacteria and arbuscular mycorrhizal fungi. This response involved activation of the proteins related to redox metabolism and suppression of excessive nodule formation. In turn, the low-responsive genotype k-3358 demonstrated a pronounced inoculation-induced suppression of protein metabolism and enhanced diverse defense reactions in pea roots under the same soil conditions. The results of the study shed light on the molecular basis of differential symbiotic responsivity in different pea cultivars.
The Impact of Prompt Engineering and Generative AI-driven tool on Autonomous Learning: A Case Study
Authors: Mzwri Kovan , Turcsányi-Szabo Márta
Published: December 2024

This study evaluates I Learn with Prompt Engineering, a self-regulated course designed to equip university students with skills in prompt engineering to effectively utilize large language models (LLMs), foster self-directed learning, and enhance academic English proficiency through generative AI applications. By integrating prompt engineering concepts with generative AI tools, the course supports autonomous learning and addresses critical skill gaps in language proficiency and market-ready capabilities. The study also examines EnSmart, an AI-driven tool powered by GPT-4 and integrated into Canvas LMS, which automates academic test content generation, grading, and delivers real-time, human-like feedback. Structured questionnaires and surveys were used to evaluate the course’s impact on prompting skills, academic English proficiency, and overall learning experiences. Results demonstrated significant improvements in prompt engineering skills, with accessible patterns like “Persona” proving highly effective, while advanced patterns such as “Flipped Interaction” posed challenges. Gains in academic English were most notable among students with lower initial proficiency, though engagement and practice time varied. Students valued EnSmart’s intuitive integration and grading accuracy but identified limitations in question diversity and adaptability. The findings highlight generative AI's potential to enhance autonomous learning and task automation, emphasizing the necessity of human oversight for ethical and effective implementation in education.
The Effect of Bone-Modifying Agents on Post-Bone Metastasis Survival
Authors: Tamiya Hironari , Nishino Kazumi , Kato Yuji , Nakahashi-Kato Reina , Kosuga-Tsujimoto Yurika , Kinoshita Shota , Watanabe Makiyo , Suzuki Rie , Wakamatsu Toru , Kakunaga Shigeki , Takenaka Satoshi
Published: December 2024

Background: Bone metastasis is associated with a poor prognosis. Bone-modifying agents (BMA) are commonly used for the prevention or treatment of skeletal-related events (SRE) in patients with bone metastasis; however, whether or not treatment with BMA improves survival remains unclear. In this study, we investigated whether BMA was involved in post-bone metastasis survival. Methods: A total of 539 cancer patients were retrospectively analyzed to identify significant in-dependent factors in post-bone metastasis survival. Results: Among the overall population, patients with the following cancers had a median survival longer than 24 months: thyroid, 97.2 months; breast, 51.5 months; prostate, 47.2 months; and kidney, 38.8 months. Treatment with BMA was a significant positive prognostic factor: BMA (-) n = 203, median post-bone metastasis survival 7.8 months (95% CI: 5.8–12.5); BMA (+) n = 336, median post-bone metastasis survival 21.9 months (95% CI: 16.1–26.4) (p < 0.001). This was particularly evident in gastrointestinal (GI) cancer (hazard ratio [HR]: 0.62, 95% CI: 0.40–0.95; p < 0.05), and non-small cell lung cancer (NSCLC) without the epidermal growth factor receptor (EGFR) mutation (HR: 0.56, 95% CI: 0.34–0.91) (p < 0.05). Con-clusions: Treatment with BMA is recommended not only for the prevention and/or treatment of SRE, but also to improve survival, particularly in cancers with typically poor post-bone metastasis sur-vival such as GI cancer and NSCLC without the EGFR mutation.
Multiple Time-Scale Pattern Classification Using a Refinement Fuzzy Min-Max Neural Network
Authors: Li Zheng , Han Yibing , Wu Xiaolong
Published: December 2024

This paper proposes a multiple time-scale pattern classification method based on a refinement fuzzy min-max neural network (RFMMNN). The purpose is to provide the suitable hyperboxes for RFMMNN to cover the multiple time-scale input patterns in the online learning algorithms. Firstly, a new fuzzy production rule (FPR) with local and global weights is established based on the multi-time scale input pattern. This FPR can directly use multi-scale features for pattern classification. Secondly, a fuzzy min-max network (FMM) with an enhanced learning algorithm is developed, and the FMM is used to refine the local and global parameters of FPR. Thirdly, a pruning strategy is designed to prevent the useless FPR generation in the learning process, and further to improve the accuracy of classification. The efficacy of FFMMNN is evaluated using benchmark data sets and a real-world task. The results are better than those from various FMM-based models, such as support vector machine-based, Bayesian-based, decision tree-based, fuzzy-based, and neural-based classifiers.
Foxp3 in the Immune System
Authors: Sato Yohei
Published: December 2024

Regulatory T cells (Tregs) play a central role in immune regulation and tolerance. The transcription factor FOXP3 is a master regulator of Tregs in both humans and mice. Mutations in FOXP3 lead to the development of IPEX syndrome in humans and the scurfy phenotype in mice, both of which are characterized by fatal systemic autoimmunity. Additionally, Treg dysfunction and FOXP3 expression instability have been implicated in non-genetic autoimmune diseases, including graft-versus-host disease, inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. Recent investigations have explored FOXP3 expression in allergic diseases, revealing Treg alterations in food allergies, asthma, and atopic dermatitis. This review examines the multifaceted roles of FOXP3 and Tregs in health and various pathological states including autoimmune disorders, allergic diseases, and cancer. Additionally, this review focuses on the impact of recent technological advancements in facilitating Treg-mediated cell and gene therapy approaches, including CRISPR/Cas9-based gene editing. The critical function of FOXP3 in maintaining immune homeostasis and tolerance to both self-antigens and alloantigens has been emphasized. Considering the potential involvement of Tregs in allergic diseases, pharmacological interventions and cell-based immunomodulatory strategies may offer promising avenues for developing novel therapeutic approaches in this field.