bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between Plant Habitat Types and Butterfly Diversity in Urban Mountain Parks
Authors: Huang Shanjun , Lin Ying , Dong Jiaying , Lin Yuxin , Su Ziang , Li Junyi , Zhang Yanqin , Jin Jiali , Fu Weicong
Published: August 2024

Butterflies serve as valuable indicators of urban ecosystem quality. Due to their accessibility, they also provide urban residents with essential opportunities to connect with nature, fulfilling social functions such as education and recreation, which significantly contribute to city dwellers’ physical and mental well-being. Urban mountain parks are critical habitats for butterflies; analyzing their spatial and temporal distribution and the impact of plant elements is crucial for enhancing plant landscape quality and butterfly diversity. The main results were as follows: (1) A monthly butterfly survey was carried out over the course of a year in the seven urban mountain parks of Fuzhou City. This survey recorded 46 species of butterflies from 36 genera across 7 families, totaling 2506 butterflies. (2) Among the seven habitat types analyzed, TS-, T-, and SG-habitats exhibited elevated levels of butterfly diversity, richness, abundance, and evenness. There were variations in butterfly evenness, diversity, richness, and abundance observed between these habitats. With the exception of N-habitat, there was a consistent seasonal pattern in butterfly diversity across different habitat types. (3) Butterfly diversity and abundance were significantly correlated with vegetation habitat factors across the tree, shrub, and herb layers. Multiple regression modeling using the Akaike information criterion revealed that arbor layer vegetation factors were present in the top four models for butterfly diversity, richness, abundance, and evenness. (4) The quality assessment of different habitat types ranked habitats as follows: TS-habitat > SG-habitat > TSG-habitat > T-habitat > TG-habitat > G-habitat = N-habitat.
Comparative Study of TPGS and Soluplus Polymeric Micelles Embedded in Poloxamer 407 In Situ Gels for Intranasal Administration
Authors: Sipos Bence , Földes Frézia , Budai-Szűcs Mária , Katona Gábor , Csóka Ildikó
Published: August 2024

This study aims to highlight the importance of choosing the appropriate co-polymer or co-polymer mixed combinations in order to design value-added nasal dosage forms. Local therapy of upper respiratory tract-related infections, such as nasal rhinosinusitis is of paramount importance, thus advanced local therapeutic options are required. Dexamethasone was encapsulated into three different polymeric micelle formulations: Soluplus or TPGS-only and their mixed combinations. Dynamic light scattering measurements proved that the particles have a micelle size less than 100 nm in monodisperse distribution, with high encapsulation efficiency above 80% and an at least 7-fold water solubility increase. Tobramycin, as an antimicrobial agent, was co-formulated into the in situ gelling systems which were optimized based on gelation time and gelation temperature. The sol–gel transition takes place between 32–35 °C, which is optimally below the temperature of the nasal cavity in a quick manner below 5 min, a suitable strategic criterion against the mucociliary clearance. In vitro drug release and permeability studies confirmed a rapid kinetics in the case of the encapsulated dexamethasone accompanied with a sustained release of tobramycin, as the hydrophilic drug.
Impact of Long-Term Pyriproxyfen Exposure on the Genetic Structure and Diversity of Aedes aegypti and Aedes albopictus in Manaus, Amazonas, Brazil
Authors: Leles Lorena Ferreira de Oliveira , Alvarez Marcus Vinícius Niz , Cortes Jose Joaquin Carvajal , Alonso Diego Peres , Ribolla Paulo Eduardo Martins , Luz Sérgio Luiz Bessa
Published: August 2024

Aedes aegypti and Aedes albopictus are responsible for transmitting major human arboviruses such as Dengue, Zika, and Chikungunya, posing a global threat to public health. The lack of etiological treatments and efficient vaccines makes vector control strategies essential for reducing vector population density and interrupting the pathogen transmission cycle. This study evaluated the impact of long-term pyriproxyfen exposure on the genetic structure and diversity of Ae. aegypti and Ae. albopictus mosquito populations. The study was conducted in Manaus, Amazonas, Brazil, where pyriproxyfen dissemination stations have been monitored since 2014 up to the present day. Double digest restriction-site associated DNA sequencing was performed, revealing that despite significant local population reductions by dissemination stations with pyriproxyfen in various locations in Brazil, focal intervention has no significant impact on the population stratification of these vectors in urban scenarios. The genetic structuring level of Ae. aegypti suggests it is more stratified and directly affected by pyriproxyfen intervention, while for Ae. albopictus exhibits a more homogeneous and less structured population. The results suggest that although slight differences are observed among mosquito subpopulations, intervention focused on neighborhoods in a capital city is not efficient in terms of genetic structuring, indicating that larger-scale pyriproxyfen interventions should be considered for more effective urban mosquito control.
Radiation-Tolerant Fibrivirga spp. from Rhizosphere Soil: Genome Insights and Potential in Agriculture
Authors: Srinivasan Sathiyaraj
Published: August 2024

The rhizosphere of plants contains a wide range of microorganisms that can be cultivated and used for the benefit of agricultural practices. From garden soil near the rhizosphere region, Strain ES10-3-2-2 was isolated, and the cells were Gram-negative, aerobic, non-spore-forming rods that were 0.3–0.8 µm in diameter and 1.5–2.5 µm in length. The neighbor-joining method on 16S rDNA similarity revealed that the strain exhibited the highest sequence similarities with “Fibrivirga algicola JA-25” (99.2%) and Fibrella forsythia HMF5405T (97.3%). To further explore its biotechnological potentialities, we sequenced the complete genome of this strain employing the PacBio RSII sequencing platform. The genome of Strain ES10-3-2-2 comprises a 6,408,035 bp circular chromosome with a 52.8% GC content, including 5038 protein-coding genes and 52 RNA genes. The sequencing also identified three plasmids measuring 212,574 bp, 175,683 bp, and 81,564 bp. Intriguingly, annotations derived from the NCBI-PGAP, eggnog, and KEGG databases indicated the presence of genes affiliated with radiation-resistance pathway genes and plant-growth promotor key/biofertilization-related genes regarding Fe acquisition, K and P assimilation, CO2 fixation, and Fe solubilization, with essential roles in agroecosystems, as well as genes related to siderophore regulation. Additionally, T1SS, T6SS, and T9SS secretion systems are present in this species, like plant-associated bacteria. The inoculation of Strain ES10-3-2-2 to Arabidopsis significantly increases the fresh shoot and root biomass, thereby maintaining the plant quality compared to uninoculated controls. This work represents a link between radiation tolerance and the plant-growth mechanism of Strain ES10-3-2-2 based on in vitro experiments and bioinformatic approaches. Overall, the radiation-tolerant bacteria might enable the development of microbiological preparations that are extremely effective at increasing plant biomass and soil fertility, both of which are crucial for sustainable agriculture.
Phosphorus-Use-Efficiency Gene Identification in Fabaceae and RSL2 Expansion in Lupinus albus Is Associated with Low-Phosphorus Adaptation
Authors: Li Xing , Yang Jinyong , Zhang Qian , Zhang Lingkui , Cheng Feng , Xu Weifeng
Published: August 2024

Phosphorus is critical for plant growth but often becomes less accessible due to its precipitation with cations in soil. Fabaceae, a diverse plant family, exhibits robust adaptability and includes species like Lupinus albus, known for its efficient phosphorus utilization via cluster roots. Here, we systematically identified phosphorus-utilization-efficiency (PUE) gene families across 35 Fabaceae species, highlighting significant gene amplification in PUE pathways in Fabaceae. Different PUE pathways exhibited variable amplification, evolution, and retention patterns among various Fabaceae crops. Additionally, the number of homologous genes of the root hair development gene RSL2 in L. albus was far more than that in other Fabaceae species. Multiple copies of the RSL2 gene were amplified and retained in L. albus after whole genome triplication. The gene structure and motifs specifically retained in L. albus were different from homologous genes in other plants. Combining transcriptome analysis under low-phosphorus treatment, it was found that most of the homologous genes of RSL2 in L. albus showed high expression in the cluster roots, suggesting that the RSL2 gene family plays an important role in the adaptation process of L. albus to low-phosphorus environments and the formation of cluster roots.
Ethical and Legal Challenges in Caring for Older Adults with Multimorbidities: Best Practices for Nurses
Authors: Alodhialah Abdulaziz M. , Almutairi Ashwaq A. , Almutairi Mohammed
Published: August 2024

This study explores the ethical and legal challenges faced by nurses in caring for older adults with multimorbidities, focusing on issues related to patient autonomy, polypharmacy, and end-of-life care. Through semi-structured interviews with 15 nurses in Riyadh, Saudi Arabia, the research highlights the complexities of obtaining informed consent from patients with cognitive impairments and the ethical dilemmas of balancing autonomy and safety. The management of polypharmacy emerged as a significant concern, with nurses emphasizing the importance of thorough documentation and coordination among healthcare providers to prevent adverse drug interactions. End-of-life care and advance directives posed further challenges, particularly when family members disagreed with patients’ documented wishes. The study underscores the need for comprehensive strategies, including ongoing education, clear communication, and supportive institutional policies, to address these issues effectively. The findings suggest that enhancing nurses’ understanding of ethical principles and legal requirements is crucial for improving patient care and ensuring compliance with regulatory standards. Future research should aim to develop evidence-based guidelines to support nursing practice in managing these ethical and legal challenges.
Unveiling the Mechanisms for Campylobacter jejuni Biofilm Formation Using a Stochastic Mathematical Model
Authors: Dzianach Paulina A. , Dykes Gary A. , Strachan Norval J. C. , Forbes Ken J. , Pérez-Reche Francisco J.
Published: August 2024

Campylobacter jejuni plays a significant role in human health, food production, and veterinary practice. Biofilm formation is a likely mechanism explaining the survival of C. jejuni in seemingly unfavourable environments, but the underlying mechanisms are poorly understood. We propose a mathematical model to unify various observations regarding C. jejuni biofilm formation. Specifically, we present a cellular automaton with stochastic dynamics that describes both the probability of biofilm initiation and its subsequent growth. Our model incorporates fundamental processes such as cell rearrangement, diffusion of chemical compounds, accumulation of extracellular material, cell growth, lysis, and deactivation due to nutrient scarcity. The model predicts an optimal nutrient concentration that enhances population survival, revealing a trade-off where higher nutrient levels may harm individual cells but benefit the overall population. Our results suggest that the lower biofilm accumulation observed experimentally in aerobic conditions compared to microaerobic conditions may be due to a reduced surface invasion probability of individual cells. However, cells that do manage to invade can generate microcolonies of a similar size under both aerobic and microaerobic conditions. These findings provide new insights into the survival probability and size of C. jejuni biofilms, suggesting potential targets for controlling its biofilm formation in various environments.
Quantitative Definition of Low-Health-Interest Populations by Using Regression Trees: A Nationwide Internet Survey in Japan
Authors: Nishizawa Yoko , Yamada Takuya , Sugimoto Kumi , Ozawa Chie , Tabuchi Takahiro , Ishikawa Hirono , Fukuda Yoshiharu
Published: August 2024

Background: Reducing health disparities is a public health issue. Identification of low-health-interest populations is important, but a definition of people with low health interest has not yet been established. We aimed to quantitatively define low-health-interest populations. Methods: A nationwide cross-sectional internet survey was conducted in 2022. We compiled regression tree (RT) analyses with/without adjustment for age, sex, and socioeconomic status with the 12-item Interest in Health Scale (IHS, score range 12–48) as an explanatory variable and the 10 composite health behaviors as a dependent variable. We defined the first IHS branching condition from the root node as a lower-health-interest group and the terminal node with the lowest health behaviors as the lowest-health-interest group. Results: The mean IHS value of 22,263 analyzed participants was 32.1 ± 5.6; it was higher in females and in those who were aged over 45 years, had a high education, a high income, or a spouse. The first branching condition was IHS 31.5, and the terminal node branched at 24.5, before/after adjustment for covariates. Conclusions: We determined the cutoff values of the IHS as <32 for a lower-health-interest group and <25 for the lowest-health-interest group. Using these cutoffs might enable us to reveal the characteristics of low-health-interest populations.
Melatonin Alleviates Liver Mitochondrial Dysfunction in Leptin-Deficient Mice
Authors: de Luxán-Delgado Beatriz , Potes Yaiza , Rubio-González Adrian , Solano Juan José , Boga José Antonio , Antuña Eduardo , Cachán-Vega Cristina , Bermejo-Millo Juan Carlos , Menéndez-Coto Nerea , García-González Claudia , Pereira Gonçalo C. , Caballero Beatriz , Coto-Montes Ana , Vega-Naredo Ignacio
Published: August 2024

Despite efforts to elucidate the cellular adaptations induced by obesity, cellular bioenergetics is currently considered a crucial target. New strategies to delay the onset of the hazardous adaptations induced by obesity are needed. Therefore, we evaluated the effects of 4 weeks of melatonin treatment on mitochondrial function and lipid metabolism in the livers of leptin-deficient mice. Our results revealed that the absence of leptin increased lipid storage in the liver and induced significant mitochondrial alterations, which were ultimately responsible for defective ATP production and reactive oxygen species overproduction. Moreover, leptin deficiency promoted mitochondrial biogenesis, fusion, and outer membrane permeabilization. Melatonin treatment reduced the bioenergetic deficit found in ob/ob mice, alleviating some mitochondrial alterations in the electron transport chain machinery, biogenesis, dynamics, respiration, ATP production, and mitochondrial outer membrane permeabilization. Given the role of melatonin in maintaining mitochondrial homeostasis, it could be used as a therapeutic agent against adipogenic steatosis.
Immunophenotypical Characterization of Limbal Mesenchymal Stromal Cell Subsets during In Vitro Expansion
Authors: Aghazadeh Sara , Peng Qiuyue , Dardmeh Fereshteh , Hjortdal Jesper Østergaard , Zachar Vladimir , Alipour Hiva
Published: August 2024

Limbal mesenchymal stromal cells (LMSCs) reside in the limbal niche, supporting corneal integrity and facilitating regeneration. While mesenchymal stem/stromal cells (MSCs) are used in regenerative therapies, there is limited knowledge about LMSC subpopulations and their characteristics. This study characterized human LMSC subpopulations through the flow cytometric assessment of fifteen cell surface markers, including MSC, wound healing, immune regulation, ASC, endothelial, and differentiation markers. Primary LMSCs were established from remnant human corneal transplant specimens and passaged eight times to observe changes during subculture. The results showed the consistent expression of typical MSC markers and distinct subpopulations with the passage-dependent expression of wound healing, immune regulation, and differentiation markers. High CD166 and CD248 expressions indicated a crucial role in ocular surface repair. CD29 expression suggested an immunoregulatory role. Comparable pigment-epithelial-derived factor (PEDF) expression supported anti-inflammatory and anti-angiogenic roles. Sustained CD201 expression indicated maintained differentiation capability, while VEGFR2 expression suggested potential endothelial differentiation. LMSCs showed higher VEGF expression than fibroblasts and endothelial cells, suggesting a potential contribution to ocular surface regeneration through the modulation of angiogenesis and inflammation. These findings highlight the heterogeneity and multipotent potential of LMSC subpopulations during in vitro expansion, informing the development of standardized protocols for regenerative therapies and improving treatments for ocular surface disorders.
Enhanced Late INa Induces Intracellular Ion Disturbances and Automatic Activity in the Guinea Pig Pulmonary Vein Cardiomyocytes
Authors: Saito Taro , Suzuki Mahiru , Ohba Aiko , Hamaguchi Shogo , Namekata Iyuki , Tanaka Hikaru
Published: August 2024

The effects of enhanced late INa, a persistent component of the Na+ channel current, on the intracellular ion dynamics and the automaticity of the pulmonary vein cardiomyocytes were studied with fluorescent microscopy. Anemonia viridis toxin II (ATX- II), an enhancer of late INa, caused increases in the basal Na+ and Ca2+ concentrations, increases in the number of Ca2+ sparks and Ca2+ waves, and the generation of repetitive Ca2+ transients. These phenomena were inhibited by eleclazine, a blocker of the late INa; SEA0400, an inhibitor of the Na+/Ca2+ exchanger (NCX); H89, a protein kinase A (PKA) inhibitor; and KN-93, a Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor. These results suggest that enhancement of late INa in the pulmonary vein cardiomyocytes causes disturbance of the intracellular ion environment through activation of the NCX and Ca2+-dependent enzymes. Such mechanisms are probably involved in the ectopic electrical activity of the pulmonary vein myocardium.
Dietary Effects on the Gut Phageome
Authors: Howard Andrea , Carroll-Portillo Amanda , Alcock Joe , Lin Henry C.
Published: August 2024

As knowledge of the gut microbiome has expanded our understanding of the symbiotic and dysbiotic relationships between the human host and its microbial constituents, the influence of gastrointestinal (GI) microbes both locally and beyond the intestine has become evident. Shifts in bacterial populations have now been associated with several conditions including Crohn’s disease (CD), Ulcerative Colitis (UC), irritable bowel syndrome (IBS), Alzheimer’s disease, Parkinson’s Disease, liver diseases, obesity, metabolic syndrome, anxiety, depression, and cancers. As the bacteria in our gut thrive on the food we eat, diet plays a critical role in the functional aspects of our gut microbiome, influencing not only health but also the development of disease. While the bacterial microbiome in the context of disease is well studied, the associated gut phageome—bacteriophages living amongst and within our bacterial microbiome—is less well understood. With growing evidence that fluctuations in the phageome also correlate with dysbiosis, how diet influences this population needs to be better understood. This review surveys the current understanding of the effects of diet on the gut phageome.
Modifying Membranotropic Action of Antimicrobial Peptide Gramicidin S by Star-like Polyacrylamide and Lipid Composition of Nanocontainers
Authors: Vashchenko Olga V. , Berest Volodymyr P. , Sviechnikova Liliia V. , Kutsevol Nataliya V. , Kasian Natalia A. , Sofronov Dmitry S. , Skorokhod Oleksii
Published: August 2024

Gramicidin S (GS), one of the first discovered antimicrobial peptides, still shows strong antibiotic activity after decades of clinical use, with no evidence of resistance. The relatively high hemolytic activity and narrow therapeutic window of GS limit its use in topical applications. Encapsulation and targeted delivery may be the way to develop the internal administration of this drug. The lipid composition of membranes and non-covalent interactions affect GS’s affinity for and partitioning into lipid bilayers as monomers or oligomers, which are crucial for GS activity. Using both differential scanning calorimetry (DSC) and FTIR methods, the impact of GS on dipalmitoylphosphatidylcholine (DPPC) membranes was tested. Additionally, the combined effect of GS and cholesterol on membrane characteristics was observed; while dipalmitoylphosphatydylglycerol (DPPG) and cerebrosides did not affect GS binding to DPPC membranes, cholesterol significantly altered the membrane, with 30% mol concentration being most effective in enhancing GS binding. The effect of star-like dextran-polyacrylamide D-g-PAA(PE) on GS binding to the membrane was tested, revealing that it interacted with GS in the membrane and significantly increased the proportion of GS oligomers. Instead, calcium ions affected GS binding to the membrane differently, with independent binding of calcium and GS and no interaction between them. This study shows how GS interactions with lipid membranes can be effectively modulated, potentially leading to new formulations for internal GS administration. Modified liposomes or polymer nanocarriers for targeted GS delivery could be used to treat protein misfolding disorders and inflammatory conditions associated with free-radical processes in cell membranes.
Drug Delivery Strategies for Age-Related Diseases
Authors: Yoshihara Kenichi , Horiguchi Michiko
Published: August 2024

Drug delivery systems (DDSs) enable the controlled release of drugs in the body. DDSs have attracted increasing attention for the treatment of various disorders, including cancer, inflammatory diseases, and age-related diseases. With recent advancements in our understanding of the molecular mechanisms of aging, new target molecules and drug delivery carriers for age-related diseases have been reported. In this review, we will summarize the recent research on DDSs for age-related diseases and identify DDS strategies in the treatment of age-related diseases.
Studying Pathogenetic Contribution of a Variant of Unknown Significance, p.M659I (c.1977G > A) in MYH7, to the Development of Hypertrophic Cardiomyopathy Using CRISPR/Cas9-Engineered Isogenic Induced Pluripotent Stem Cells
Authors: Pavlova Sophia V. , Shulgina Angelina E. , Zakian Suren M. , Dementyeva Elena V.
Published: August 2024

Hypertrophic cardiomyopathy (HCM) is a cardiovascular pathology that is caused by variants in genes encoding sarcomere-associated proteins. However, the clinical significance of numerous variants in HCM-associated genes is still unknown. CRISPR/Cas9 is a tool of nucleotide sequence editing that allows for the unraveling of different biological tasks. In this study, introducing a mutation with CRISPR/Cas9 into induced pluripotent stem cells (iPSCs) of a healthy donor and the directed differentiation of the isogenic iPSC lines into cardiomyocytes were used to assess the pathogenicity of a variant of unknown significance, p.M659I (c.1977G > A) in MYH7, which was found previously in an HCM patient. Using two single-stranded donor oligonucleotides with and without the p.M659I (c.1977G > A) mutation, together with CRISPR/Cas9, an iPSC line heterozygous at the p.M659I (c.1977G > A) variant in MYH7 was generated. No CRISPR/Cas9 off-target activity was observed. The iPSC line with the introduced p.M659I (c.1977G > A) mutation in MYH7 retained its pluripotent state and normal karyotype. Compared to the isogenic control, cardiomyocytes derived from the iPSCs with the introduced p.M659I (c.1977G > A) mutation in MYH7 recapitulated known HCM features: enlarged size, elevated diastolic calcium level, changes in the expression of HCM-related genes, and disrupted energy metabolism. These findings indicate the pathogenicity of the variant.
Genome-Wide Analysis of the Gibberellin-Oxidases Family Members in Four Prunus Species and a Functional Analysis of PmGA2ox8 in Plant Height
Authors: Li Xue , Zhang Jie , Guo Xiaoyu , Qiu Like , Chen Ke , Wang Jia , Cheng Tangren , Zhang Qixiang , Zheng Tangchun
Published: August 2024

Gibberellins (GAs), enzymes that play a significant role in plant growth and development, and their levels in plants could be regulated by gibberellin-oxidases (GAoxs). As important fruit trees and ornamental plants, the study of the mechanism of plant architecture formation of the Prunus genus is crucial. Here, 85 GAox genes were identified from P. mume, P. armeniaca, P. salicina, and P. persica, and they were classified into six subgroups. Conserved motif and gene structure analysis showed that GAoxs were conserved in the four Prunus species. Collinearity analysis revealed two fragment replication events of PmGAoxs in the P. mume genome. Promoter cis-elements analysis revealed 24 PmGAoxs contained hormone-responsive elements and development regulatory elements. The expression profile indicated that PmGAoxs have tissue expression specificity, and GA levels during the dormancy stage of flower buds were controlled by certain PmGAoxs. After being treated with IAA or GA3, the transcription level of PmGA2ox8 in stems was significantly increased and showed a differential expression level between upright and weeping stems. GUS activity driven by PmGA2ox8 promoter was detected in roots, stems, leaves, and flower organs of Arabidopsis. PmGA2ox8 overexpression in Arabidopsis leads to dwarfing phenotype, increased number of rosette leaves but decreased leaf area, and delayed flowering. Our results showed that GAoxs were conserved in Prunus species, and PmGA2ox8 played an essential role in regulating plant height.
Three Years On: The Role of Pegcetacoplan in Paroxysmal Nocturnal Hemoglobinuria (PNH) since Its Initial Approval
Authors: Horneff Regina , Czech Barbara , Yeh Michael , Surova Elena
Published: August 2024

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by complement-mediated hemolysis and potentially life-threatening complications. Pegcetacoplan, an inhibitor of complement components C3 and C3b, was approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2021. A recent expansion to its indication by the EMA has made pegcetacoplan available for the treatment of both complement inhibitor-naïve and -experienced patients with PNH who have hemolytic anemia, a similarly broad patient population as in the US. This approval was based on results from the Phase 3 PEGASUS study, where pegcetacoplan showed superiority over the C5 inhibitor eculizumab with regard to improving the hemoglobin level in patients with anemia despite eculizumab treatment, and the Phase 3 PRINCE study, where pegcetacoplan showed superiority over supportive care with regard to hemoglobin stabilization and improving the lactate dehydrogenase level in complement inhibitor-naïve patients. In light of this recent indication expansion by the EMA, this article describes how the strong efficacy of pegcetacoplan is linked to its mechanism of action, which provides broad hemolysis control over both intravascular and extravascular hemolysis to improve a range of disease markers and enhance patients’ quality of life. Furthermore, additional data and learnings obtained from over 3 years of experience with pegcetacoplan are summarized, including long-term efficacy and safety results, real-world clinical experiences, pharmacokinetic characteristics, and extensive practical guidance for the first-to-market proximal complement inhibitor for PNH.
Long-Term Oral Administration of Hyperimmune Egg-Based IgY-Rich Formulations Induces Mucosal Immune Response and Systemic Increases of Cytokines Involved in Th2- and Th17-Type Immune Responses in C57BL/6 Mice
Authors: Nastasa Valentin , Minea Bogdan , Pasca Aurelian-Sorin , Bostanaru-Iliescu Andra-Cristina , Stefan Alina-Elena , Gologan Daniela , Capota Robert , Foia Liliana-Georgeta , Mares Mihai
Published: August 2024

Three hyperimmune egg-based formulations rich in immunoglobulin Y (IgY) were orally administered (daily, for up to 90 days) to C57BL/6 mice that were not microbially challenged. The serum levels of 32 cytokines were quantified every 30 days. Histopathology, hematology, and serum biochemistry investigations were also performed. As a sign of increased immune activity, lymphohistiocytic infiltrates were detected in the digestive tract and the liver after 30, 60, and 90 days of treatment. These infiltrates were also present in the lungs after 30 and 60 days, but not at 90 days. Blood analysis indicated systemic inflammation after 30 days of treatment: increases in pro-inflammatory cytokines, glycemia, total serum proteins, ALT, and ALP. After 60 and 90 days of treatment, the analyzed blood parameters showed mixed signs of both increased and decreased inflammation. The increased cytokines, which varied with formulation and time of exposure, indicated a combination of mostly Th17- and Th2-type immune responses. As the mice were healthy and housed in standardized sanitary conditions, and were not microbially challenged, the data were consistent with an interaction of IgY with the gut-associated lymphoid tissue as the main mechanism of action. This interaction generated a local immune response, which subsequently induced a systemic response.
Integrated Transcriptomic–Metabolomic Analysis Reveals the Effect of Different Light Intensities on Ovarian Development in Chickens
Authors: Zhou Xiaoli , Xu Yuhang , Fang Cheng , Ye Chutian , Liang Weiming , Fan Zhexia , Ma Xuerong , Liu Aijun , Zhang Xiquan , Luo Qingbin
Published: August 2024

Light is a key environmental factor regulating reproduction in avians. However, the mechanism of light intensity regulating ovarian development is still unclear. In this study, 5-week-old (5 wk) partridge broiler breeders were randomly divided into a low-light-intensity group (LL group) and a natural-light-intensity group (NL group) (n = 100). In the rearing period (5 wk to 22 wk), the light intensity of the LL group and NL group were 0.41 ± 0.05 lux and 45.39 ± 1.09 lux, and in the laying period (23 wk to 32 wk) they were 23.92 ± 0.06 lux and 66.93 ± 0.76 lux, respectively. Samples were collected on 22 wk and 32 wk. The results showed that the LL group had a later age at first egg and a longer laying period than the NL group. Serum P4 and LH levels in the LL group were higher than in the NL group on 22 wk (p < 0.05). On 32 wk, P4, E2, LH and FSH levels in the LL group were lower than in the NL group (p < 0.05). Ovarian transcriptomics and metabolomics identified 128 differentially expressed genes (DEGs) and 467 differential metabolites (DMs) on 22 wk; 155 DEGs and 531 DMs on 32 wk between two groups. An enrichment analysis of these DEGs and DMs identified key signaling pathways, including steroid hormone biosynthesis, neuroactive ligand-receptor interaction. In these pathways, genes such as CYP21A1, SSTR2, and NPY may regulate the synthesis of metabolites, including tryptamine, triglycerides, and phenylalanine. These genes and metabolites may play a dominant role in the light-intensity regulation of ovarian development and laying performance in broiler breeders.
Iron–Sulfur Clusters: Assembly and Biological Roles
Authors: Maio Nunziata
Published: August 2024

Iron–sulfur (Fe-S) clusters are critical to a wide range of biological processes, from DNA repair and transcriptional regulation to mitochondrial respiration and enzymatic catalysis [...]
Clinical Impact of Intracoronary Imaging in the Management of Stent Thrombosis
Authors: Karamasis Grigoris V. , Katsikis Athanasios , Konstantinou Klio , Clesham Gerald J. , Kelly Paul A. , Jagathesan Rohan , Prati Francesco , Bourantas Christos V. , Davies John R. , Keeble Thomas R.
Published: August 2024

Objectives: Use of intracoronary imaging (ICI) in cases of stent thrombosis (ST) is recommended and tailored treatment appears reasonable. Nevertheless, data supporting such a strategy are lacking. The aim of this study was to evaluate the clinical impact of ICI in the management of ST. Methods: The unadjusted study population was consecutive patients with definite ST presenting in a single tertiary cardiac centre and undergoing percutaneous coronary intervention (PCI). The presumed major mechanism of ST was assigned according to the real-time ICI interpretation by the PCI operator. Propensity score matching was performed with regard to ICI use to form the adjusted population and Kaplan–Meier analysis was applied to compare survival free of cardiac death (CD) or target lesion revascularization (TLR). Results: The unadjusted population included 130 ST patients, with the majority presenting with ST-elevation myocardial infarction (STEMI) (88%) and very late ST (86%). ICI was performed in 45 patients, of whom optical coherence tomography (OCT) was performed in 30 cases. When the individual ST mechanisms were viewed as groups, there was an interaction observed between type of treatment (stent vs. non-stent) and ST mechanism, with non-stent treatment being more prevalent in cases of underexpansion, malapposition, in-stent restenosis and mechanism uncertainty. After application of matching, two groups of 30 patients were formed. ICI-guided management resulted in better survival free of CD–TLR at 2 years (93% vs. 73%, p = 0.037). Conclusions: Intracoronary imaging guidance during PCI for ST had a direct impact on management (stent vs. non-stent) and resulted in a lower event rate at mid-term follow-up when propensity matched analysis was applied.
Nonadherence to Cardiovascular Drugs Predicts Risk for Non-Arthritic Anterior Ischemic Optic Neuropathy: A Large-Scale National Study
Authors: Hammud Anan , Haviv Yosef. S. , Walter Eyal , Amitai Nir , Kerman Tomer , Leeman Samuel , Tsumi Erez
Published: August 2024

Purpose: While patients with cardiovascular comorbidities are at a higher risk for the occurrence of non-arteritic anterior ischemic optic neuropathy (NAION), it is unclear whether adherence to medication results in risk reduction. The purpose of this study was to investigate whether nonadherence to medical therapy for cardiovascular morbidity correlates with a higher risk for NAION when compared to patients with strict adherence. Methods: A retrospective case-control study was conducted among members of Clalit Health Services in Israel from 2001 to 2022. For each of the 757 NAION cases, three controls (totaling 2271 patients) were matched based on birth year and sex, with a propensity score analysis employed to adjust for a range of comorbidities. A patient was deemed nonadherent with medical treatment if their purchased quantity of medication was less than 60% of the prescribed annual dosage. Mixed models were used to evaluate exposure differences, and conditional logistic regression was applied, incorporating adjustments for socioeconomic status and ethnicity, to examine the impact of medication nonadherence on NAION risk. Results: A total of 3028 patients were included in the study; 757 patients with the diagnosis of NAION and 2271 in the matched control group. The average age of NAION patients was 69 ± 9 years and 55% were male. After adjustments for socioeconomic status and ethnicity, nonadherence to calcium channel blockers (CCBs) (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.03–1.71) and anti-arrhythmic (OR: 5.67, 95% CI: 1.89–21.2) medications emerged as significant risk factors. Similarly, nonadherence to cardioprotective medications (OR: 1.46, 95% CI: 1.23–1.74) was also identified as a significant risk factor. Conclusions: Nonadherence to treatments for cardiovascular disease, specifically to medications known to improve prognosis, is associated with a higher risk for NAION.
Subjective Symptoms and Disease Activity Related to Serum Zinc Concentration in Primary Sjögren’s Syndrome
Authors: Akiya Kumiko , Nishihara Masahiro , Nagasawa Yosuke , Kitamura Noboru , Kitano Hisataka , Shoji Jun , Iwabuchi Yu , Hao Hiroyuki , Nakamura Hideki
Published: August 2024

Background/Objectives: We examined the frequency of zinc deficiency in patients with Sjögren’s syndrome (SS) and the relationship between zinc deficiency and each of the subjective symptoms and disease activity. Methods: We enrolled 164 patients aged ≥ 20 years with primary SS (pSS) based on the revised diagnostic criteria of the Ministry of Health, Labor and Welfare (1999) and 144 patients with RA diagnosed according to the ACR/EULAR classification criteria for RA (2010) as a comparison group. Subjective symptoms were confirmed using an original questionnaire, and disease activity was determined using the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index (ESSDAI). The serum zinc concentrations were measured in both SS and RA patients. Results: The rate of zinc deficiency in the SS group was 26.1%, significantly higher than that in the RA group (7.6%). The rate of zinc deficiency was significantly higher in the pSS group compared with Japanese health checkup recipients reported in the literature. The mean serum zinc concentration in primary SS was 60.6 ± 7.3 µmol/L in the high disease activity group with an ESSDAI of ≥5 points, which was significantly lower than the concentration of 69.7 ± 10.2 µmol/L in patients with an ESSDAI of ≤4 points. Conclusions: The frequency of zinc deficiency was higher in patients with pSS than in patients with RA. Disease activity was also higher in patients with zinc deficiency, suggesting an association between zinc concentration and organ involvement in pSS.
Neuropelveology for Endometriosis Management: A Systematic Review and Multilevel Meta-Analysis
Authors: Allahqoli Leila , Hakimi Sevil , Momenimovahed Zohre , Mazidimoradi Afrooz , Rezaei Fatemeh , Aghamohammadi Seyedeh Zahra , Rahmani Azam , Mansouri Ghazal , Hadavandsiri Fatemeh , Salehiniya Hamid , Alkatout Ibrahim
Published: August 2024

Background: Despite the availability of treatments such as surgery and hormonal therapy, women with endometriosis often endure chronic problems. This review aims to evaluate the effectiveness and safety of neuropelveology. Methods: In a systematic review with a meta-analysis, we searched three electronic databases: MEDLINE (PubMed), Scopus, Embase, and Web of Science (WOS). The search was conducted in January 2024 with no date or language restrictions using a carefully curated set of keywords. We conducted a comprehensive review, including all observational and clinical trials reporting data on neuropelveology approaches in the management of endometriosis, irrespective of geographical location. The studies included in our review were required to be published in peer-reviewed journals and be available in any language, with at least an abstract in English. The data of all included studies were summarized in excel (version 19) and were analyzed by Comprehensive Meta-analysis v3.3 (Biostat) and STATA (version 17). A multilevel meta-analysis was performed on studies with two arms (intervention and control) to evaluate the efficacy of neuropelveology in managing women with endometriosis. Results: After screening 476 records, 30 studies, published from 1952 to 2021, were included in this review, each employing various methodologies. The studies were divided into the following three categories: (a) efficacy of neurectomy or nerve resection (n = 20), (b) efficacy of neurolysis (nerve blocks) (n = 4), and (c) efficacy of neuromodulation (n = 6) in the management of endometriosis. Among the studies evaluating the efficacy of neurectomy or nerve resection, 10 studies (with 18 group comparisons) were included in the random-effects meta-analysis. Treatment success (not occurrence of pain) was higher with neurectomy vs. controls (RR = 0.497, 95% CI = 0.236 to 1.04, p = 0.06 (for experimental studies) and RR = 0.248, 95% CI = 0.14 to 0.43, p < 0.001 (for observational studies)), representing a 50% and 75.2% risk reduction in the recurrence of pain in experimental and observational studies, respectively. Similarly, neurolysis, particularly superior hypogastric plexus blocks and uterine nerve ethanol neurolysis, demonstrated encouraging outcomes in pain reduction and an improved quality of life for women with endometriosis. The efficacy of neuromodulation in managing endometriosis symptoms appears promising but requires further investigation. Conclusions: In conclusion, neuropelveology approaches, such as neurectomy, neurolysis, and neuromodulation, offer significant potential for pain reduction in endometriosis patients, albeit with risks of complications and high recurrence rates, necessitating careful patient selection and long-term monitoring.
Sensory Profiles Predict Symptoms of Central Sensitization in Low Back Pain: A Predictive Model Research Study
Authors: Gräper Pieter J. , Scafoglieri Aldo , Clark Jacqueline R. , Hallegraeff Joannes M.
Published: August 2024

Background: Acute low back pain has a high prevalence, and when persisting into chronicity, it results in enormous socio-economic consequences. Sensory preferences may be key factors in predicting central sensitization as the main mechanism of nociplastic pain and chronicity. Objectives: Build a model to predict central sensitization symptoms using sensory profiles based on the PROGRESS framework. Methods: A Prognostic Model Research study was carried out to predict central sensitization symptoms at 12 weeks, using baseline sensory profiles, based on 114 patients with acute low back pain. Independent variables were sensory profiles, state and trait anxiety, age, duration, pain severity, depressive symptoms, and pain catastrophizing. Results: This model, based on continuous data, significantly predicts central sensitization symptoms at 12 weeks. It contains two significantly contributing variables: sensory profile Sensory Sensitive (unstandardized B-value = 0.42; p = 0.01) and trait anxiety (unstandardized B-value = 0.53; p ≤ 0.001). The model has a predictive value of R2 = 0.38. Conclusions: This model significantly predicts central sensitization symptoms based on sensory profile Sensory Sensitive and trait anxiety. This model may be a useful tool to intervene in a bottom–up and top–down approaches to prevent chronicity in clinical practice, including individual sensory preferences and behavioral responses to sensory stimulation in rehabilitation strategies.
The Manganese–Bone Connection: Investigating the Role of Manganese in Bone Health
Authors: Taskozhina Gulaim , Batyrova Gulnara , Umarova Gulmira , Issanguzhina Zhamilya , Kereyeva Nurgul
Published: August 2024

The complex relationship between trace elements and skeletal health has received increasing attention in the scientific community. Among these minerals, manganese (Mn) has emerged as a key element affecting bone metabolism and integrity. This review examines the multifaceted role of Mn in bone health, including its effects on bone regeneration, mineralization, and overall skeletal strength. This review article is based on a synthesis of experimental models, epidemiologic studies, and clinical trials of the mechanisms of the effect of Mn on bone metabolism. Current research data show that Mn is actively involved in the processes of bone remodeling by modulating the activity of osteoblasts and osteoclasts, as well as the main cells that regulate bone formation and resorption. Mn ions have a profound effect on bone mineralization and density by intricately regulating signaling pathways and enzymatic reactions in these cells. Additionally, Mn superoxide dismutase (MnSOD), located in bone mitochondria, plays a crucial role in osteoclast differentiation and function, protecting osteoclasts from oxidative damage. Understanding the nuances of Mn’s interaction with bone is essential for optimizing bone strategies, potentially preventing and managing skeletal diseases. Key findings include the stimulation of osteoblast proliferation and differentiation, the inhibition of osteoclastogenesis, and the preservation of bone mass through the RANK/RANKL/OPG pathway. These results underscore the importance of Mn in maintaining bone health and highlight the need for further research into its therapeutic potential.
Retinitis Pigmentosa and Therapeutic Approaches: A Systematic Review
Authors: Confalonieri Filippo , La Rosa Antonio , Ottonelli Giovanni , Barone Gianmaria , Ferraro Vanessa , Di Maria Alessandra , Romano Mary , Randazzo Alessandro , Vallejo-Garcia Josè Luis , Vinciguerra Paolo , Petrovski Goran
Published: August 2024

Background: Retinitis pigmentosa (RP) is a group of hereditary retinal dystrophies characterized by progressive degeneration of photoreceptor cells, which results in debilitating visual impairment. This systematic review aims to evaluate the efficacy and safety of emerging treatment modalities for RP, including gene therapy, mesenchymal-cell-based approaches, and supplementary interventions. Methods: A comprehensive search of electronic databases was conducted to identify relevant studies published up to February 2024. Studies reporting outcomes of treatment interventions for RP, including randomized controlled trials, non-randomized studies, and case series, were included. Data extraction and synthesis were performed according to predefined criteria, focusing on assessing the quality of evidence and summarizing key findings. Results: The search yielded 13 studies meeting inclusion criteria, encompassing diverse treatment modalities and study designs. Gene therapy emerged as a promising therapeutic approach, with several studies reporting favorable outcomes regarding visual function preservation and disease stabilization. Mesenchymal-cell-based therapies also demonstrated potential benefits, although evidence remains limited and heterogeneous. Supplementary interventions, including nutritional supplements and neuroprotective agents, exhibited variable efficacy, with conflicting findings across studies. Conclusions: Despite the lack of definitive curative treatments, emerging therapeutic modalities promise to slow disease progression and preserve visual function in individuals with RP. However, substantial gaps in evidence and heterogeneity in study methodologies underscore the need for further research to elucidate optimal treatment strategies, refine patient selection criteria, and enhance long-term outcomes. This systematic review provides a comprehensive synthesis of current evidence and highlights directions for future research to advance the care and management of individuals with RP.