bluuebunny/crossref_metadata_2025 huggingface dataset:
Soil-Microbial CNP Content and Ecological Stoichiometry Characteristics of Typical Broad-Leaved Tree Communities in Fanjing Mountain in Spring
Authors: Luo Wenmin , Wu Xianliang , Chen Sheng , Mu Guiting , Liu Yingying
Published: April 2024

This study aims to investigate the impact of diverse forest stand types and soil depths on soil ecological stoichiometry characteristics, shedding light on nutrient limitations and cycling patterns within the mid-subtropical forest ecosystem in southwest China during spring. The research focused on four representative forest stands situated in Fanjing Mountain: Castanopsis fargesii (C. fargesii), Cyclobalanopsis multiervis (C. multiervis), Cyclobalanopsis argyrotricha (C. argyrotricha), and Rhododendron argyrophyllum Franch (R. argyrophyllum). Sample plots were established in these forest types, and soil samples were collected from the 0–20 cm and 20–40 cm soil layers in March, spring of 2023. Various soil parameters, including pH, soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), soil microbial biomass carbon (MBC), soil microbial nitrogen (MBN), and soil microbial phosphorus (MBP) were measured, and their stoichiometric ratios were calculated. The findings of the study were as follows: (1) In the 0–20 cm soil layer, C. argyrotricha exhibited the highest soil organic carbon, followed by C. fargesii, C. multiervis, and R. argyrophyllum with the lowest content. No significant differences in soil organic carbon were observed among the four forests in the 20–40 cm soil layer. Additionally, C. argyrotricha displayed a significantly higher soil C:N ratio compared to other forest types in different soil layers. In the typical broad-leaved forest area of Fanjing Mountain, the TP was classified as deficient. (2) In the 0–20 cm soil layer, the MBC of C. fargesii surpassed C. multiervis, C. argyrotricha, and R. argyrophyllum by 26.59%, 42.92%, and 24.67%, respectively. There were no significant differences in soil MBC:MBP ratio and MBN:MBP ratio, regardless of forest species and soil depths. The low availability of soil nitrogen in different forest stand types in Fanjing Mountain strongly limits soil microorganism biomass. (3) The correlation between SOC, TN, TP, and their stoichiometric ratios varied across different soil layers. Therefore, in managing the Fanjing Mountain forest area, attention should be paid to supplementing N and P in the soil.
Efficient Constant Envelope Precoding for Massive MU-MIMO Downlink via Majorization-Minimization Method
Authors: Liang Rui , Li Hui , Dong Yingli , Xue Guodong
Published: April 2024

The practical implementation of massive multi-user multi-input–multi-output (MU-MIMO) downlink communication systems power amplifiers that are energy efficient; otherwise, the power consumption of the base station (BS) will be prohibitive. Constant envelope (CE) precoding is gaining increasing interest for its capability to utilize low-cost, high-efficiency nonlinear radio frequency amplifiers. Our work focuses on the topic of CE precoding in massive MU-MIMO systems and presents an efficient CE precoding algorithm. This algorithm uses an alternating minimization (AltMin) framework to optimize the CE precoded signal and precoding factor, aiming to minimize the difference between the received signal and the transmit symbol. For the optimization of the CE precoded signal, we provide a powerful approach that integrates the majorization-minimization (MM) method and the fast iterative shrinkage-thresholding (FISTA) method. This algorithm combines the characteristics of the massive MU-MIMO channel with the second-order Taylor expansion to construct the surrogate function in the MM method, in which minimizing this surrogate function is the worst-case of the system. Specifically, we expand the suggested CE precoding algorithm to involve the discrete constant envelope (DCE) precoding case. In addition, we thoroughly examine the exact property, convergence, and computational complexity of the proposed algorithm. Simulation results demonstrate that the proposed CE precoding algorithm can achievean uncoded biterror rate (BER) performance gain of roughly 1dB compared to the existing CE precoding algorithm and has an acceptable computational complexity. This performance advantage also exists when it comes to DCE precoding.
Mitigating Missing Rate and Early Cyberattack Discrimination Using Optimal Statistical Approach with Machine Learning Techniques in a Smart Grid
Authors: Murugesan Nakkeeran , Velu Anantha Narayanan , Palaniappan Bagavathi Sivakumar , Sukumar Balamurugan , Hossain Md. Jahangir
Published: April 2024

In the Industry 4.0 era of smart grids, the real-world problem of blackouts and cascading failures due to cyberattacks is a significant concern and highly challenging because the existing Intrusion Detection System (IDS) falls behind in handling missing rates, response times, and detection accuracy. Addressing this problem with an early attack detection mechanism with a reduced missing rate and decreased response time is critical. The development of an Intelligent IDS is vital to the mission-critical infrastructure of a smart grid to prevent physical sabotage and processing downtime. This paper aims to develop a robust Anomaly-based IDS using a statistical approach with a machine learning classifier to discriminate cyberattacks from natural faults and man-made events to avoid blackouts and cascading failures. The novel mechanism of a statistical approach with a machine learning (SAML) classifier based on Neighborhood Component Analysis, ExtraTrees, and AdaBoost for feature extraction, bagging, and boosting, respectively, is proposed with optimal hyperparameter tuning for the early discrimination of cyberattacks from natural faults and man-made events. The proposed model is tested using the publicly available Industrial Control Systems Cyber Attack Power System (Triple Class) dataset with a three-bus/two-line transmission system from Mississippi State University and Oak Ridge National Laboratory. Furthermore, the proposed model is evaluated for scalability and generalization using the publicly accessible IEEE 14-bus and 57-bus system datasets of False Data Injection (FDI) attacks. The test results achieved higher detection accuracy, lower missing rates, decreased false alarm rates, and reduced response time compared to the existing approaches.
The Nitrogen Cycle of a Cool-Temperate Deciduous Broad-Leaved Forest
Authors: Cao Ruoming , Chen Siyu , Yoshitake Shinpei , Onishi Takeo , Iimura Yasuo , Ohtsuka Toshiyuki
Published: April 2024

The nitrogen (N) cycle, a major biogeochemical cycle in forest ecosystems, notably affects ecosystem multifunctionality. However, the magnitude and role of organic N and the snow season remain uncertain in this cycle. We assessed the N flux and pool data of a temperate deciduous broad-leaved forest to clarify N cycle processes. The results showed that the most important component of the N pool was the soil N pool. The N demand of the site amounted to 139.4 kg N ha−1 year−1 and was divided into tree production (83.8%) and bamboo production (16.2%). We clarified that retranslocation (37.4%), mineralization at a soil depth of 0–5 cm (15.3%), litter leachate (4.6%), throughfall (2.3%), and canopy uptake (0.5%) provided 60.1% of the N demand. In terms of soil at 0–5 cm in depth, the net mineralization rate during the snow season contributed to 30% of the annual mineralization. We concluded that the study site was not N-saturated as a result of a positive N input–output flux budget. More than half of the total N was accounted for by dissolved organic N flowing through several pathways, indicating that organic N plays a vital role in the cycle. The mineralization rate in the soil layer during the snow season is an important link in the N cycle.
Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry: An Innovative Tool for Rapid Identification of Hylurgus ligniperda, an Invasive Pest
Authors: Wang Jianlin , Tao Jing , Dong Zhijun , Zhu Jiaqiang
Published: April 2024

Hylurgus ligniperda is an imported quarantine plant pest in China. Its identification is usually based on morphological characteristics; therefore, species identification needs high professional requirements of staff and professionals with high experience accumulated through long-term training. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a rapid identification technology, which is based on protein profiles of species. It has been widely used for the identification of pathogenic microorganisms. Many studies have reported the identification of mosquitoes, ticks, and other arthropods. The application of MALDI-TOF MS in the identification of H. ligniperda can improve the identification efficiency of H. ligniperda, preventing and control its harm and further spread. To construct a spectra database for H. ligniperda, we analyzed the effect of different factors, such as different body parts, developmental stages, populations, and preservation conditions, on its protein spectrum. We collected protein spectrum profiles from 19 specimens of H. ligniperda and its related species, obtaining 211 protein spectra to construct a reference database and validate identification. The protein spectrum from the chest specimens of H. ligniperda showed many peaks, high intensity, and a stable signal, indicating a successful data establishment. The difference in protein spectra between different regions of the same species was less, but did not affect the identification results. Clear differences were observed in the protein spectrum across many developmental stages. The database established by the adult specimens protein spectrum can accurately identify Dendroctonus valens, Tomicus piniperda, and H. ligniperda. MALDI-TOF MS technology can be used for the rapid identification of H. ligniperda. This method is rapid and direct, and the identification results are robust. It does not require specialized entomological expertise and can be used for customs interception and field investigations.
Fixed Point Theorems: Exploring Applications in Fractional Differential Equations for Economic Growth
Authors: Abdou Afrah Ahmad Noman
Published: April 2024

The aim of this research is to introduce two new notions, Θ-(Ξ,h)-contraction and rational (α,η)-ψ-interpolative contraction, in the setting of F-metric space and to establish corresponding fixed point theorems. To reinforce understanding and highlight the novelty of our findings, we provide a non-trivial example that not only supports the obtained results but also illuminates the established theory. Finally, we apply our main result to discuss the existence and uniqueness of solutions for a fractional differential equation describing an economic growth model.
The Pathogenesis of Pancreatitis and the Role of Autophagy
Authors: Tsomidis Ioannis , Voumvouraki Argyro , Kouroumalis Elias
Published: April 2024

The pathogenesis of acute and chronic pancreatitis has recently evolved as new findings demonstrate a complex mechanism operating through various pathways. In this review, the current evidence indicating that several mechanisms act in concert to induce and perpetuate pancreatitis were presented. As autophagy is now considered a fundamental mechanism in the pathophysiology of both acute and chronic pancreatitis, the fundamentals of the autophagy pathway were discussed to allow for a better understanding of the pathophysiological mechanisms of pancreatitis. The various aspects of pathogenesis, including trypsinogen activation, ER stress and mitochondrial dysfunction, the implications of inflammation, and macrophage involvement in innate immunity, as well as the significance of pancreatic stellate cells in the development of fibrosis, were also analyzed. Recent findings on exosomes and the miRNA regulatory role were also presented. Finally, the role of autophagy in the protection and aggravation of pancreatitis and possible therapeutic implications were reviewed.
Information Provision Regarding Health-Related Direct-to-Consumer Genetic Testing for Dutch Consumers: An in-Depth Content Analysis of Sellers’ Websites
Authors: Bruins Danny , Onstwedder Suzanne M. , Cornel Martina C. , Ausems Margreet G. E. M. , van Mil Marc H. W. , Rigter Tessel
Published: April 2024

Background: Previous studies have suggested that information offered by sellers of health-related direct-to-consumer genetic tests (DTC-GTs) is often incomplete, unbalanced, or too difficult to understand. The extent to which this is the case for sellers accessible to Dutch consumers has not previously been studied. Methods and Goals: The present study aimed to assess the completeness, balance, readability, and findability of informational content on a selection of websites from several health-related DTC-GT sellers accessible to Dutch consumers. An in-depth content analysis was performed based on a recently published checklist outlining key items for policy guidance regarding DTC-GT services. Results: The information provided by sellers did not equally cover all aspects relevant to health-related DTC-GT service provision. The provided information was slightly unbalanced, with benefits of health-related DTC-GT usage being overemphasized compared to its risks and limitations. The readability of the provided information was low, on average requiring college education for proper understanding. A findability analysis showed that information concerning all themes is overall relatively evenly distributed across analyzed sellers’ websites. Conclusions: Information provision by assessed health-related DTC-GT sellers is suboptimal regarding completeness, balance, and readability. To better empower potential consumers to make an informed decision regarding health-related DTC-GT usage, we advocate industry-wide enhancement of information provision.
Single-Nucleus Transcriptome Profiling from the Hippocampus of a PTSD Mouse Model and CBD-Treated Cohorts
Authors: Xie Guanbo , Qin Yihan , Wu Ning , Han Xiao , Li Jin
Published: April 2024

Post-traumatic stress disorder (PTSD) is the most common psychiatric disorder after a catastrophic event; however, the efficacious treatment options remain insufficient. Increasing evidence suggests that cannabidiol (CBD) exhibits optimal therapeutic effects for treating PTSD. To elucidate the cell-type-specific transcriptomic pathology of PTSD and the mechanisms of CBD against this disease, we conducted single-nucleus RNA sequencing (snRNA-seq) in the hippocampus of PTSD-modeled mice and CBD-treated cohorts. We constructed a mouse model by adding electric foot shocks following exposure to single prolonged stress (SPS+S) and tested the freezing time, anxiety-like behavior, and cognitive behavior. CBD was administrated before every behavioral test. The PTSD-modeled mice displayed behaviors resembling those of PTSD in all behavioral tests, and CBD treatment alleviated all of these PTSD-like behaviors (n = 8/group). Three mice with representative behavioral phenotypes were selected from each group for snRNA-seq 15 days after the SPS+S. We primarily focused on the excitatory neurons (ExNs) and inhibitory neurons (InNs), which accounted for 68.4% of the total cell annotations. A total of 88 differentially upregulated genes and 305 differentially downregulated genes were found in the PTSD mice, which were found to exhibit significant alterations in pathways and biological processes associated with fear response, synaptic communication, protein synthesis, oxidative phosphorylation, and oxidative stress response. A total of 63 overlapping genes in InNs were identified as key genes for CBD in the treatment of PTSD. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the anti-PTSD effect of CBD was related to the regulation of protein synthesis, oxidative phosphorylation, oxidative stress response, and fear response. Furthermore, gene set enrichment analysis (GSEA) revealed that CBD also enhanced retrograde endocannabinoid signaling in ExNs, which was found to be suppressed in the PTSD group. Our research may provide a potential explanation for the pathogenesis of PTSD and facilitate the discovery of novel therapeutic targets for drug development. Moreover, it may shed light on the therapeutic mechanisms of CBD.
A Co-Created Assessment Framework to Measure Inclusive Health and Wellbeing in a Vulnerable Context in the South of Europe
Authors: Mac Fadden Isotta , Cocchioni Roberta , Delgado-Serrano María Mar
Published: April 2024

Rapid urbanisation exacerbates health and wellbeing disparities in vulnerable contexts and underscores the imperative need to develop innovative and participatory co-creation approaches to understand and address the specificities of these contexts. This paper presents a method to develop an assessment framework that integrates top-down dimensions with bottom-up perspectives to monitor the impact of inclusive health and wellbeing interventions tailored to the neighbourhood’s needs in Las Palmeras, a vulnerable neighbourhood in Cordoba (Spain). Drawing upon studies in the literature examining urban health and wellbeing trends, it delineates a participatory and inclusive framework, emphasising the need for context-specific indicators and assessment tools. Involving diverse stakeholders, including residents and professionals, it enriches the process and identifies key indicators and assessment methods. This approach provides valuable insights for managing innovative solutions, aligning them with local expectations, and measuring their impact. It contributes to the discourse on inclusive urban health by advocating for participatory, context-specific strategies and interdisciplinary collaboration. While not universally applicable, the framework offers a model for health assessment in vulnerable contexts, encouraging further development of community-based tools for promoting inclusive wellbeing.
An Exploration of People Living with Parkinson’s Experience of Cardio-Drumming; Parkinson’s Beats: A Qualitative Phenomenological Study
Authors: Irons J. Yoon , Williams Alison , Holland Jo , Jones Julie
Published: April 2024

Research has shown that physical activity has a range of benefits for people living with Parkinson’s (PLwP), improving muscle strength, balance, flexibility, and walking, as well as non-motor symptoms such as mood. Parkinson’s Beats is a form of cardio-drumming, specifically adapted for PLwP, and requires no previous experience nor skills. Nineteen PLwP (aged between 55 and 80) took part in the regular Parkinson’s Beats sessions in-person or online. Focus group discussions took place after twelve weeks to understand the impacts of Parkinson’s Beats. Through the framework analysis, six themes and fifteen subthemes were generated. Participants reported a range of benefits of cardio-drumming, including improved fitness and movement, positive mood, the flow experience, and enhanced social wellbeing. A few barriers to participation were also reported. Future research is justified, and best practice guidelines are needed to inform healthcare professionals, PLwP and their care givers.
Effects of Standardized Patient Simulation and Mobile Applications on Nursing Students’ Clinical Competence, Self-Efficacy, and Cultural Competence: A Quasi-Experimental Study
Authors: Ton Duc Nu Minh , Duong Trang Thi Kieu , Tran Hang Thi , Nguyen Thanh Thi Thanh , Mai Hai Ba , Nguyen Phuong Thi Anh , Ho Binh Duy , Ho Trang Thi Thuy
Published: April 2024

Background: Simulation-based education has emerged as an effective approach in nursing education worldwide. We aimed to evaluate the effectiveness of a surgical nursing education program based on a simulation using standardized patients and mobile applications among nursing students. Methods: A mixed-methods design with a quasi-experimental longitudinal approach and focus group interviews was employed. The data were collected from 130 third-year nursing students at three different time points who were equally divided into experimental and control groups. This study measured the level of clinical surgical nursing competence, self-efficacy in clinical performance, cultural competence, and satisfaction with simulation experience. Four focus group interviews were conducted using open-ended questions to explore the participants’ perspectives on the course’s efficacy and satisfaction. Results: There were statistically significant differences in clinical surgical nursing competence (F = 8.68, p < 0.001), self-efficacy in clinical performance (F = 13.56, p < 0.001), and cultural competence (F = 10.35, p < 0.001) across time between the intervention and control groups. Student satisfaction with the simulation-based training was high, particularly regarding debriefing and reflection, with an overall mean satisfaction level of 4.25 (0.40). Students’ perspectives regarding integrated hybrid training are categorized into three themes: educational achievement, dynamic learning experiences, and satisfaction and suggestion. Conclusion: Simulation-based learning provides a dynamic and immersive educational experience that enables undergraduate nursing students to develop and refine essential clinical skills while also fostering confidence and cultural competence.
Comprehensive Research on Druggable Proteins: From PSSM to Pre-Trained Language Models
Authors: Chu Hongkang , Liu Taigang
Published: April 2024

Identification of druggable proteins can greatly reduce the cost of discovering new potential drugs. Traditional experimental approaches to exploring these proteins are often costly, slow, and labor-intensive, making them impractical for large-scale research. In response, recent decades have seen a rise in computational methods. These alternatives support drug discovery by creating advanced predictive models. In this study, we proposed a fast and precise classifier for the identification of druggable proteins using a protein language model (PLM) with fine-tuned evolutionary scale modeling 2 (ESM-2) embeddings, achieving 95.11% accuracy on the benchmark dataset. Furthermore, we made a careful comparison to examine the predictive abilities of ESM-2 embeddings and position-specific scoring matrix (PSSM) features by using the same classifiers. The results suggest that ESM-2 embeddings outperformed PSSM features in terms of accuracy and efficiency. Recognizing the potential of language models, we also developed an end-to-end model based on the generative pre-trained transformers 2 (GPT-2) with modifications. To our knowledge, this is the first time a large language model (LLM) GPT-2 has been deployed for the recognition of druggable proteins. Additionally, a more up-to-date dataset, known as Pharos, was adopted to further validate the performance of the proposed model.
Differential Response of Human Dendritic Cells upon Stimulation with Encapsulated or Non-Encapsulated Isogenic Strains of Porphyromonas gingivalis
Authors: Melgar-Rodríguez Samanta , Polanco Alan , Ríos-Muñoz Jearitza , García Michelle , Sierra-Cristancho Alfredo , González-Osuna Luis , Díaz-Zúñiga Jaime , Carvajal Paola , Vernal Rolando , Bravo Denisse
Published: April 2024

During periodontitis, the extracellular capsule of Porphyromonas gingivalis favors alveolar bone loss by inducing Th1 and Th17 patterns of lymphocyte response in the infected periodontium. Dendritic cells recognize bacterial antigens and present them to T lymphocytes, defining their activation and polarization. Thus, dendritic cells could be involved in the Th1 and Th17 response induced against the P. gingivalis capsule. Herein, monocyte-derived dendritic cells were obtained from healthy individuals and then stimulated with different encapsulated strains of P. gingivalis or two non-encapsulated isogenic mutants. Dendritic cell differentiation and maturation were analyzed by flow cytometry. The mRNA expression levels for distinct Th1-, Th17-, or T-regulatory-related cytokines and transcription factors, as well as TLR2 and TLR4, were assessed by qPCR. In addition, the production of IL-1β, IL-6, IL-23, and TNF-α was analyzed by ELISA. The encapsulated strains and non-encapsulated mutants of P. gingivalis induced dendritic cell maturation to a similar extent; however, the pattern of dendritic cell response was different. In particular, the encapsulated strains of P. gingivalis induced higher expression of IRF4 and NOTCH2 and production of IL-1β, IL-6, IL-23, and TNF-α compared with the non-encapsulated mutants, and thus, they showed an increased capacity to trigger Th1 and Th17-type responses in human dendritic cells.
pH-Sensitive Amphiphilic Diblock Polyphosphoesters with Lactate Units: Synthesis and Application as Drug Carriers
Authors: Mochizuki Kasumi , Mitova Violeta , Makino Kimiko , Terada Hiroshi , Takeuchi Issei , Troev Kolio
Published: April 2024

pH-sensitive amphiphilic diblock polyphosphoesters containing lactic acid units were synthesized by multistep one-pot polycondensation reactions. They comprise acid-labile P(O)-O-C and C(O)-O-C bonds, the cleavage of which depends on the pH of the medium. The structure of these copolymers was characterized by 1H, 13C {H}, 31P NMR, and size exclusion chromatography (SEC). The newly synthesized polymers self-assembled into the micellar structure in an aqueous solution. The effects of the molecular weight of the copolymer and the length of the hydrophobic chain on micelle formation and stabilityand micelle size were studied via dynamic light scattering (DLS). Drug loading and encapsulation efficiency tests using doxorubicin revealed that hydrophobic drugs can be delivered by copolymers. It was established that the molecular weight of the copolymer, length of the hydrophobic chain and content of lactate units affects the size of the micelles, drug loading, and efficiency of encapsulation. A copolymer with 10.7% lactate content has drug loading (3.2 ± 0.3) and efficiency of encapsulation (57.4 ± 3.2), compared to the same copolymer with 41.8% lactate content (1.63%) and (45.8%), respectively. It was demonstrated that the poly[alkylpoly(ethylene glycol) phosphate-b-alkylpoly(ethylene glycol)lactate phosphate] DOX system has a pH-sensitive response capability in the result in which DOX was selectively accumulated into the tumor, where pH is acidic. The results obtained indicate that amphiphilic diblock polyphosphoesters have potential as drug carriers.
Targeting the High-Density Lipoprotein Proteome for the Treatment of Post-Acute Sequelae of SARS-CoV-2
Authors: Grote Karsten , Schaefer Ann-Christin , Soufi Muhidien , Ruppert Volker , Linne Uwe , Mukund Bhagwat Aditya , Szymanski Witold , Graumann Johannes , Gercke Yana , Aldudak Sümeya , Hilfiker-Kleiner Denise , Schieffer Elisabeth , Schieffer Bernhard
Published: April 2024

Here, we target the high-density lipoprotein (HDL) proteome in a case series of 16 patients with post-COVID-19 symptoms treated with HMG-Co-A reductase inhibitors (statin) plus angiotensin II type 1 receptor blockers (ARBs) for 6 weeks. Patients suffering from persistent symptoms (post-acute sequelae) after serologically confirmed SARS-CoV-2 infection (post-COVID-19 syndrome, PCS, n = 8) or following SARS-CoV-2 vaccination (PVS, n = 8) were included. Asymptomatic subjects with corresponding serological findings served as healthy controls (n = 8/8). HDL was isolated using dextran sulfate precipitation and the HDL proteome of all study participants was analyzed quantitatively by mass spectrometry. Clinical symptoms were assessed using questionnaires before and after therapy. The inflammatory potential of the patients’ HDL proteome was addressed in human endothelial cells. The HDL proteome of patients with PCS and PVS showed no significant differences; however, compared to controls, the HDL from PVS/PCS patients displayed significant alterations involving hemoglobin, cytoskeletal proteins (MYL6, TLN1, PARVB, TPM4, FLNA), and amyloid precursor protein. Gene Ontology Biological Process (GOBP) enrichment analysis identified hemostasis, peptidase, and lipoprotein regulation pathways to be involved. Treatment of PVS/PCS patients with statins plus ARBs improved the patients’ clinical symptoms. After therapy, three proteins were significantly increased (FAM3C, AT6AP2, ADAM10; FDR < 0.05) in the HDL proteome from patients with PVS/PCS. Exposure of human endothelial cells with the HDL proteome from treated PVS/PCS patients revealed reduced inflammatory cytokine and adhesion molecule expression. Thus, HDL proteome analysis from PVS/PCS patients enables a deeper insight into the underlying disease mechanisms, pointing to significant involvement in metabolic and signaling disturbances. Treatment with statins plus ARBs improved clinical symptoms and reduced the inflammatory potential of the HDL proteome. These observations may guide future therapeutic strategies for PVS/PCS patients.
Elucidating the Role of Wildtype and Variant FGFR2 Structural Dynamics in (Dys)Function and Disorder
Authors: Lian Yiyang , Bodian Dale , Shehu Amarda
Published: April 2024

The fibroblast growth factor receptor 2 (FGFR2) gene is one of the most extensively studied genes with many known mutations implicated in several human disorders, including oncogenic ones. Most FGFR2 disease-associated gene mutations are missense mutations that result in constitutive activation of the FGFR2 protein and downstream molecular pathways. Many tertiary structures of the FGFR2 kinase domain are publicly available in the wildtype and mutated forms and in the inactive and activated state of the receptor. The current literature suggests a molecular brake inhibiting the ATP-binding A loop from adopting the activated state. Mutations relieve this brake, triggering allosteric changes between active and inactive states. However, the existing analysis relies on static structures and fails to account for the intrinsic structural dynamics. In this study, we utilize experimentally resolved structures of the FGFR2 tyrosine kinase domain and machine learning to capture the intrinsic structural dynamics, correlate it with functional regions and disease types, and enrich it with predicted structures of variants with currently no experimentally resolved structures. Our findings demonstrate the value of machine learning-enabled characterizations of structure dynamics in revealing the impact of mutations on (dys)function and disorder in FGFR2.
Profiling of Tumour-Infiltrating Lymphocytes and Tumour-Associated Macrophages in Ovarian Epithelial Cancer—Relation to Tumour Characteristics and Impact on Prognosis
Authors: Stout Annabel , Facey Natalya , Bhatnagar Anjali , Rice Kirstie , Berditchevski Fedor , Kearns Daniel , Metcalf Amy , Elghobashy Alaa , Shaaban Abeer M.
Published: April 2024

Early evidence suggests a strong impact of tumour-infiltrating lymphocytes (TILs) on both the prognosis and clinical behaviour of ovarian cancer. Proven associations, however, have not yet translated to successful immunotherapies and further work in the field is urgently needed. We aimed to analyse the tumour microenvironment of a well-characterised cohort of ovarian cancer samples. Tumour markers were selected owing to their comparative underrepresentation in the current literature. Paraffin-embedded, formalin-fixed tumour tissue blocks of 138 patients representative of the population and including early stage disease were identified, stained for CD3, CD20, CD68 and CD163 and analysed for both the stromal and intertumoral components. Data were statistically analysed in relation to clinical details, histological subtype, borderline vs. malignant status, survival and management received. Mean stromal CD3, total CD3 count, mean stromal CD20 and total CD20 count all correlated negatively with survival. Malignant ovarian tumours consistently demonstrated significantly higher infiltration of all analysed immune cells than borderline tumours. Assessment of the stromal compartment produced a considerably higher proportion of significant results when compared to the intra-tumoural infiltrates. Customary assessment of solely intra-tumoural cells in advanced stage disease patients undergoing primary debulking surgery should be challenged, with recommendations for future scoring systems provided.
Essential Role of COPII Proteins in Maintaining the Contractile Ring Anchoring to the Plasma Membrane during Cytokinesis in Drosophila Male Meiosis
Authors: Matsuura Yoshiki , Kaizuka Kana , Inoue Yoshihiro H.
Published: April 2024

Coatomer Protein Complex-II (COPII) mediates anterograde vesicle transport from the endoplasmic reticulum (ER) to the Golgi apparatus. Here, we report that the COPII coatomer complex is constructed dependent on a small GTPase, Sar1, in spermatocytes before and during Drosophila male meiosis. COPII-containing foci co-localized with transitional endoplasmic reticulum (tER)-Golgi units. They showed dynamic distribution along astral microtubules and accumulated around the spindle pole, but they were not localized on the cleavage furrow (CF) sites. The depletion of the four COPII coatomer subunits, Sec16, or Sar1 that regulate COPII assembly resulted in multinucleated cell production after meiosis, suggesting that cytokinesis failed in both or either of the meiotic divisions. Although contractile actomyosin and anilloseptin rings were formed once plasma membrane ingression was initiated, they were frequently removed from the plasma membrane during furrowing. We explored the factors conveyed toward the CF sites in the membrane via COPII-mediated vesicles. DE-cadherin-containing vesicles were formed depending on Sar1 and were accumulated in the cleavage sites. Furthermore, COPII depletion inhibited de novo plasma membrane insertion. These findings suggest that COPII vesicles supply the factors essential for the anchoring and/or constriction of the contractile rings at cleavage sites during male meiosis in Drosophila.
Proteomics Analysis of the Polyomavirus DNA Replication Initiation Complex Reveals Novel Functional Phosphorylated Residues and Associated Proteins
Authors: Dey-Rao Rama , Shen Shichen , Qu Jun , Melendy Thomas
Published: April 2024

Polyomavirus (PyV) Large T-antigen (LT) is the major viral regulatory protein that targets numerous cellular pathways for cellular transformation and viral replication. LT directly recruits the cellular replication factors involved in initiation of viral DNA replication through mutual interactions between LT, DNA polymerase alpha-primase (Polprim), and single-stranded DNA binding complex, (RPA). Activities and interactions of these complexes are known to be modulated by post-translational modifications; however, high-sensitivity proteomic analyses of the PTMs and proteins associated have been lacking. High-resolution liquid chromatography tandem mass spectrometry (LC–MS/MS) of the immunoprecipitated factors (IPMS) identified 479 novel phosphorylated amino acid residues (PAARs) on the three factors; the function of one has been validated. IPMS revealed 374, 453, and 183 novel proteins associated with the three, respectively. A significant transcription-related process network identified by Gene Ontology (GO) enrichment analysis was unique to LT. Although unidentified by IPMS, the ETS protooncogene 1, transcription factor (ETS1) was significantly overconnected to our dataset indicating its involvement in PyV processes. This result was validated by demonstrating that ETS1 coimmunoprecipitates with LT. Identification of a novel PAAR that regulates PyV replication and LT’s association with the protooncogenic Ets1 transcription factor demonstrates the value of these results for studies in PyV biology.
Leukocytes within Autologous Blood Concentrates Have No Impact on the Growth and Proliferation of Human Primary Osteoblasts: An In Vitro Study
Authors: Mourão Carlos Fernando , Dohle Eva , Bayrak Büşra , Winter Anne , Sader Robert , Ghanaati Shahram
Published: April 2024

Platelet-rich fibrin (PRF) is a widely used autologous blood concentrate in regenerative medicine. This study aimed to characterize the cellular composition and distribution of different PRF matrices generated by high (710 g) and low (44 g) relative centrifugal forces (RCFs) and to analyze their bioactivity on human primary osteoblasts (pOBs). PRF was separated into upper layer (UL) and buffy coat (BC) fractions, and their cellular contents were assessed using histological and immunohistochemical staining. The release of platelet-derived growth factor (PDGF) and transforming growth factor (TGF-β) was quantified using an ELISA. Indirect PRF treatment on pOBs was performed to evaluate cell viability and morphology. A histological analysis revealed higher quantities of leukocytes and platelets in the low-RCF PRF. TGF-β release was significantly higher in the low-RCF PRF compared to the high-RCF PRF. All PRF fractions promoted pOB proliferation regardless of the centrifugation protocol used. The low-RCF PRF showed higher TGF-β levels than the high-RCF PRF. These findings contribute to understanding the cellular mechanisms of PRF and provide insights into optimizing PRF protocols for bone regeneration, advancing regenerative medicine, and improving patient outcomes.
The Neurotranscriptome of Monochamus alternatus
Authors: Han Xiaohong , Weng Mingqing , Shi Wenchao , Wen Yingxin , Long Yirong , Hu Xinran , Ji Guoxi , Zhu Yukun , Wen Xuanye , Zhang Feiping , Wu Songqing
Published: April 2024

The Japanese pine sawyer Monochamus alternatus serves as the primary vector for pine wilt disease, a devastating pine disease that poses a significant threat to the sustainable development of forestry in the Eurasian region. Currently, trap devices based on informational compounds have played a crucial role in monitoring and controlling the M. alternatus population. However, the specific proteins within M. alternatus involved in recognizing the aforementioned informational compounds remain largely unclear. To elucidate the spatiotemporal distribution of M. alternatus chemosensory-related genes, this study conducted neural transcriptome analyses to investigate gene expression patterns in different body parts during the feeding and mating stages of both male and female beetles. The results revealed that 15 genes in the gustatory receptor (GR) gene family exhibited high expression in the mouthparts, most genes in the odorant binding protein (OBP) gene family exhibited high expression across all body parts, 22 genes in the odorant receptor (OR) gene family exhibited high expression in the antennae, a significant number of genes in the chemosensory protein (CSP) and sensory neuron membrane protein (SNMP) gene families exhibited high expression in both the mouthparts and antennae, and 30 genes in the ionotropic receptors (IR) gene family were expressed in the antennae. Through co-expression analyses, it was observed that 34 genes in the IR gene family were co-expressed across the four developmental stages. The Antenna IR subfamily and IR8a/Ir25a subfamily exhibited relatively high expression levels in the antennae, while the Kainate subfamily, NMDA subfamily, and Divergent subfamily exhibited predominantly high expression in the facial region. MalIR33 is expressed only during the feeding stage of M. alternatus, the MalIR37 gene exhibits specific expression in male beetles, the MalIR34 gene exhibits specific expression during the feeding stage in male beetles, the MalIR8 and MalIR39 genes exhibit specific expression during the feeding stage in female beetles, and MalIR8 is expressed only during two developmental stages in male beetles and during the mating stage in female beetles. The IR gene family exhibits gene-specific expression in different spatiotemporal contexts, laying the foundation for the subsequent selection of functional genes and facilitating the full utilization of host plant volatiles and insect sex pheromones, thereby enabling the development of more efficient attractants.
Effect of Trichomonacide 6-Nitro-1H-benzimidazole Derivative Compounds on Expression Level of Metabolic Genes in Trichomonas vaginalis
Authors: Gutiérrez-Cardona Jocelyn Yamin , Calderón-Jaimes Ernesto , Ortega-Cuellar Daniel , Sánchez-Carrillo Adrián , Castillo-Rodríguez Rosa Angélica , Canseco-Ávila Luis Miguel , Rocha-Ramírez Luz María , Martínez-Rosas Víctor , Gómez-Manzo Saúl , Hernández-Ochoa Beatriz
Published: April 2024

The parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide. This infection often remains asymptomatic and is related to several health complications. The traditional treatment for trichomoniasis is the use of drugs of the 5-nitroimidazole family, such as metronidazole; however, scientific reports indicate an increasing number of drug-resistant strains. Benzimidazole derivatives could offer an alternative in the search for new anti-trichomonas drugs. In this sense, two attractive candidates are the compounds O2N-BZM7 and O2N-BZM9 (1H-benzimidazole derivatives), since, through in vitro tests, they have shown a higher trichomonacide activity. In this study, we determined the effect on the expression level of metabolic genes in T. vaginalis. The results show that genes involved in redox balance (NADHOX, G6PD::6PGL) are overexpressed, as well as the gene that participates in the first reaction of glycolysis (CK); on the other hand, structural genes such as ACT and TUB are decreased in expression in trophozoites treated with the compound O2N-BZM9, which would probably affect its morphology, motility and virulence. These results align with the trichomonacidal activity of the compounds, with benzimidazole O2N-BZM9 being the most potent, with an IC50 value of 4.8 μM. These results are promising for potential future therapeutic applications.
Role of Protein Tyrosine Phosphatase Receptor Type E (PTPRE) in Chemoresistant Retinoblastoma
Authors: Mohren Lars , Doege Annika , Miroschnikov Natalia , Dräger Oliver , Busch Maike Anna , Dünker Nicole
Published: April 2024

Protein tyrosine phosphatase receptor type E (PTPRE) is a member of the “classical” protein tyrosine phosphatase subfamily and regulates a variety of cellular processes in a tissue-specific manner by antagonizing the function of protein tyrosine kinases. PTPRE plays a tumorigenic role in different human cancer cells, but its role in retinoblastoma (RB), the most common malignant eye cancer in children, remains to be elucidated. Etoposide-resistant RB cell lines and RB patients display significant higher PTPRE expression levels compared to chemosensitive counterparts and the healthy human retina, respectively. PTPRE promotor methylation analyses revealed that PTPRE expression in RB is not regulated via this mechanism. Lentiviral PTPRE knockdown (KD) induced a significant decrease in growth kinetics, cell viability, and anchorage-independent growth of etoposide-resistant Y79 and WERI RB cells. Caspase-dependent apoptosis rates were significantly increased and a re-sensitization for etoposide could be observed after PTPRE depletion. In vivo chicken chorioallantoic membrane (CAM) assays revealed decreased tumor formation capacity as well as reduced tumor size and weight following PTPRE KD. Expression levels of miR631 were significantly downregulated in etoposide-resistant RB cells and patients. Transient miR631 overexpression resulted in significantly decreased PTPRE levels and concomitantly decreased proliferation and increased apoptosis levels in etoposide-resistant RB cells. These impacts mirror PTPRE KD effects, indicating a regulation of PTPRE via this miR. Additionally, PTPRE KD led to altered phosphorylation of protein kinase SGK3 and—dependent on the cell line—AKT and ERK1/2, suggesting potential PTPRE downstream signaling pathways. In summary, these results indicate an oncogenic role of PTPRE in chemoresistant retinoblastoma.
Coenzyme Q10 and Autoimmune Disorders: An Overview
Authors: Mantle David , Hargreaves Iain P.
Published: April 2024

Some 90 autoimmune disorders have been described in medical literature, affecting most of the tissues within the body. Autoimmune disorders may be difficult to treat, and there is a need to develop novel therapeutic strategies for these disorders. Autoimmune disorders are characterised by mitochondrial dysfunction, oxidative stress, and inflammation; there is therefore a rationale for a role for coenzyme Q10 in the management of these disorders, on the basis of its key role in normal mitochondrial function, as an antioxidant, and as an anti-inflammatory agent. In this article, we have therefore reviewed the potential role of CoQ10, in terms of both deficiency and/or supplementation, in a range of autoimmune disorders.
Constructing Semantic Summaries Using Embeddings
Authors: Trouli Georgia Eirini , Papadakis Nikos , Kondylakis Haridimos
Published: April 2024

The increase in the size and complexity of large knowledge graphs now available online has resulted in the emergence of many approaches focusing on enabling the quick exploration of the content of those data sources. Structural non-quotient semantic summaries have been proposed in this direction that involve first selecting the most important nodes and then linking them, trying to extract the most useful subgraph out of the original graph. However, the current state of the art systems use costly centrality measures for identifying the most important nodes, whereas even costlier procedures have been devised for linking the selected nodes. In this paper, we address both those deficiencies by first exploiting embeddings for node selection, and then by meticulously selecting approximate algorithms for node linking. Experiments performed over two real-world big KGs demonstrate that the summaries constructed using our method enjoy better quality. Specifically, the coverage scores obtained were 0.8, 0.81, and 0.81 for DBpedia v3.9 and 0.94 for Wikidata dump 2018, across 20%, 25%, and 30% summary sizes, respectively. Additionally, our method can compute orders of magnitude faster than the state of the art.
Estimating Asset Parameters Using Levy’s Moment Matching Method
Authors: Miyake Masatoshi
Published: April 2024

Conventionally, the unknown parameters in Merton’s model are set using a calibration method that estimates the current asset value and volatility from observable stock prices. This paper describes a completely different approach for estimating these asset parameters. The proposed approach uses Levy’s moment matching method to derive an equation for the asset value based on the sum of equity and debt on the balance sheet, with the current debt value treated as an unknown and estimated from stock prices. Empirical analysis reveals that this method results in simpler calculations than the calibration method and can estimate the asset parameters and default probability to the same degree of accuracy. An additional advantage of the proposed method is that it estimates the asset correlation if the current debt value is known, allowing Merton’s model to be extended to multiple companies. The asset correlation obtained by the proposed method is estimated from multiple parameters related to equity, debt, and the evaluation period, which is useful when the influence of equity volatility, leverage, and time must be considered in estimating asset correlations based on equity correlations.