bluuebunny/crossref_metadata_2025 huggingface dataset:
Geometrothermodynamics of 3D Regular Black Holes
Authors: Beissen Nurzada
Published: May 2024

We investigate a spherically symmetric exact solution of Einstein’s gravity with cosmological constant in (2 + 1) dimensions, non-minimally coupled to a scalar field. The solution describes the gravitational field of a black hole, which is free of curvature singularities in the entire spacetime. We use the formalism of geometrothermodynamics to investigate the geometric properties of the corresponding space of equilibrium states and find their interpretation from the point of view of thermodynamics. It turns out that, as a result of the presence of thermodynamic interaction, the space of equilibrium states is curved with two possible configurations, which depend on the value of a coupling constant. In the first case, the equilibrium space is completely regular, corresponding to a stable thermodynamic system. The second case is characterized by the presence of two curvature singularities, which are shown to correspond to locations where the system undergoes two different phase transitions, one due to the breakdown of the thermodynamic stability condition and the second one due to the presence of a divergence at the level of the response functions.
Embedded Complexity of Evolutionary Sequences
Authors: Phillips Jonathan D.
Published: May 2024

Multiple pathways and outcomes are common in evolutionary sequences for biological and other environmental systems due to nonlinear complexity, historical contingency, and disturbances. From any starting point, multiple evolutionary pathways are possible. From an endpoint or observed state, multiple possibilities exist for the sequence of events that created it. However, for any observed historical sequence—e.g., ecological or soil chronosequences, stratigraphic records, or lineages—only one historical sequence actually occurred. Here, a measure of the embedded complexity of historical sequences based on algebraic graph theory is introduced. Sequences are represented as system states S(t), such that S(t − 1) ≠ S(t) ≠ S(t + 1). Each sequence of N states contains nested subgraph sequences of length 2, 3, …, N − 1. The embedded complexity index (which can also be interpreted in terms of embedded information) compares the complexity (based on the spectral radius λ1) of the entire sequence to the cumulative complexity of the constituent subsequences. The spectral radius is closely linked to graph entropy, so the index also reflects information in the sequence. The analysis is also applied to ecological state-and-transition models (STM), which represent observed transitions, along with information on their causes or triggers. As historical sequences are lengthened (by the passage of time and additional transitions or by improved resolutions or new observations of historical changes), the overall complexity asymptotically approaches λ1 = 2, while the embedded complexity increases as N2.6. Four case studies are presented, representing coastal benthic community shifts determined from biostratigraphy, ecological succession on glacial forelands, vegetation community changes in longleaf pine woodlands, and habitat changes in a delta.
Leveraging Data Locality in Quantum Convolutional Classifiers
Authors: Jeng Mingyoung , Nobel Alvir , Jha Vinayak , Levy David , Kneidel Dylan , Chaudhary Manu , Islam Ishraq , Facer Audrey , Singh Manish , Baumgartner Evan , Vanderhoof Eade , Arshad Abina , El-Araby Esam
Published: May 2024

Quantum computing (QC) has opened the door to advancements in machine learning (ML) tasks that are currently implemented in the classical domain. Convolutional neural networks (CNNs) are classical ML architectures that exploit data locality and possess a simpler structure than a fully connected multi-layer perceptrons (MLPs) without compromising the accuracy of classification. However, the concept of preserving data locality is usually overlooked in the existing quantum counterparts of CNNs, particularly for extracting multifeatures in multidimensional data. In this paper, we present an multidimensional quantum convolutional classifier (MQCC) that performs multidimensional and multifeature quantum convolution with average and Euclidean pooling, thus adapting the CNN structure to a variational quantum algorithm (VQA). The experimental work was conducted using multidimensional data to validate the correctness and demonstrate the scalability of the proposed method utilizing both noisy and noise-free quantum simulations. We evaluated the MQCC model with reference to reported work on state-of-the-art quantum simulators from IBM Quantum and Xanadu using a variety of standard ML datasets. The experimental results show the favorable characteristics of our proposed techniques compared with existing work with respect to a number of quantitative metrics, such as the number of training parameters, cross-entropy loss, classification accuracy, circuit depth, and quantum gate count.
Occurrence and Potential for Coalbed Methane Extraction in the Depocenter Area of the Upper Silesian Coal Basin (Poland) in the Context of Selected Geological Factors
Authors: Kędzior Sławomir , Teper Lesław
Published: May 2024

Coalbed methane (CBM) is the only unconventional gas in Poland with estimated recoverable resources. The prospects for developing deep CBM have been explored in recent years by drilling deep exploration wells within the depocenter of the Upper Silesian Coal Basin. The purpose of this study is to analyze the occurrence and potential for CBM extraction in this area of the basin, which can be considered prospective due to the confirmed presence of significant amounts of gas and thick coal seams at depths > 1500 m. The study examined the vertical and horizontal variability of the gas content in the studied area, the coal rank in the seams, thermal conditions, and coal reservoir parameters. The gas content in the seams, reaching more than 18 m3/t coaldaf at a depth of 2840 m, and indicative estimated gas resources of 9 billion m3 were found. The high gas content is accompanied by positive thermal and coal rank anomalies. The permeability and methane saturation of the coal seams are low, and therefore, potential methane production may prove problematic. However, the development of CBM extraction technologies involving directional drilling with artificial fracturing may encourage gas production testing in the study area.
Detection of Cavitation in a Centrifugal Pump-as-Turbine Using Time-Domain-Based Analysis of Vibration Signals
Authors: Stephen Calvin , Basu Biswajit , McNabola Aonghus
Published: May 2024

Pumps-as-Turbines (PATs) are increasingly used in micro-hydropower applications due to their cost competitiveness that is brought about by lower acquisition, design, operation, and maintenance costs. Despite these, limited research exists that investigates PAT failures. Notably, there is a literature gap concerning cavitation in PATs. As such, this study proposes an improvement to the deviation from the normal distribution (DND) technique to facilitate application in PAT cavitation detection. Probability density functions of vibration signals collected during operation at design speed and various cavitation states are developed and the DND computed using two approaches, i.e., the use of baseline data and the original method, for comparison purposes. Normal probability plots are presented to depict suitability of the two approaches in quantifying the DND. Results show higher deviation when using baseline data, hence, improved detection capabilities with amplification of the slope of the trend line under cavitating conditions when using the proposed DND approach. The proposed method also allows for establishing clear alarm limits for the condition monitoring of PATs in practice. Moreover, the proposed method is validated by application at various PAT operating speeds and cavitation states. The proposed method is found to be responsive, reliable, and independent from operating speed.
Experimental Investigation of the Impact of CO2 Injection Strategies on Rock Wettability Alteration for CCS Applications
Authors: Eyitayo Stella I. , Talal Gamadi , Kolawole Oladoyin , Okere Chinedu J. , Ispas Ion , Arbad Nachiket , Emadibaladehi Hossein , Watson Marshall C.
Published: May 2024

Carbon capture and storage (CCS) has been recognized as a pivotal technology for mitigating climate change by reducing CO2 emissions. Storing CO2 in deep saline aquifers requires preserving the water-wet nature of the formation throughout the storage period, which is crucial for maintaining rock integrity and storage efficiency. However, the wettability of formations can change upon exposure to supercritical CO2 (scCO2), potentially compromising storage efficiency. Despite extensive studies on various factors influencing wettability alteration, a significant research gap remains in understanding the effects of different CO2 injection strategies on wettability in deep saline formations (DSFs). This study addresses this gap by investigating how three distinct CO2 injection strategies—continuous scCO2 injection (CCI), water alternating with scCO2 injection (WAG), and simultaneous water and scCO2 injection (SAI)—affect the wettability of gray Berea sandstone and Indiana limestone, both selected for their homogeneous properties relevant to CCS. Using a standardized sessile drop contact angle method before and after CO2 injection, along with core flooding to model the injection process at an injection pressure of 1500 psi and temperature of 100 °F with a confining pressure of 2500 psi, the results indicate a shift in wettability towards more CO2-wet conditions for both rock types under all strategies with changes in CA of 61.6–83.4° and 77.6–87.9° and 81.5–124.2° and 94.6–128.0° for sandstone and limestone, respectively. However, the degree of change varies depending on the injection strategy: sandstone exhibits a pronounced response to the CCI strategy, with up to a 77% increase in contact angle (CA), particularly after extended exposure. At the same time, WAG shows the least change, suggesting that water introduction slows surface modification. For limestone, the changes in CA ranged from 9% to 49% across strategies, with WAG and SAI being more effective in altering its wettability. This study underscores the importance of selecting suitable CO2 injection strategies based on rock type and wettability characteristics to maximize carbon storage efficiency. The findings offer valuable insights into the complex interactions of fluid–rock systems and a guide for enhancing the design and implementation of CCS technologies in various geological settings.
Food Web Structure and Ecosystem Functions of the Water Source in the Middle Route of China’s South-to-North Water Diversion Project
Authors: Zhang Yuanyuan , Gu Kaidi , Wang Xinyu , Zhang Ji’ao , Duan Jiaoyang , Hu Zhongjun , Liu Qigen
Published: May 2024

The Danjiangkou Reservoir is the water source of the middle route of China’s South-to-North Water Diversion Project, encompassing the Dan Reservoir and Han Reservoir. However, little is known about the ecological functions of this important ecosystem. Based on a survey conducted in 2023 in the Dan Reservoir, a mass balance model was constructed using Ecopath with Ecosim 6.6 software to characterize its food web structure and ecosystem properties. The model consisted of 18 functional groups, including producers, consumers, and detritus, covering the entire process of energy flow in the ecosystem. The outputs indicated that the fractional trophic level of functional groups in the Dan Reservoir ecosystem ranged from 1.00 to 3.50. The ecotrophic efficiencies of the main economic fish species were all less than 0.9, and the ecotrophic efficiencies of phytoplankton and detritus were less than 0.5. There were two main food chains: the detritus food chain (39%) and the grazing food chain (61%). The total energy transfer efficiency between trophic levels was only 6.02%, and there was a significant phenomenon of energy transfer blockage between trophic levels II and V. Analysis of the overall characteristics of the ecosystem revealed that the total primary production to total biomass (67.96619), connectance index (0.274), and Finn’s cycling index (2.856) of the Dan Reservoir ecosystem all indicate that the ecosystem is immature, with low nutrient recycling efficiency and poor resistance to external disturbances. This may be related to the low proportion of silver carp and bighead carp in the reservoir and the unreasonable structure of the fish community. Our results suggest that it is necessary to scientifically adjust the structure of the fish community, enhance the proportion of filter-feeding and omnivorous fish to improve the energy flow efficiency, and promote the maturity and stability of the Dan Reservoir.
“Codex 4D” Project: Interdisciplinary Investigations on Materials and Colors of De Balneis Puteolanis (Angelica Library, Rome, Ms. 1474)
Authors: Pietroni Eva , Botteon Alessandra , Buti David , Chirivì Alessandra , Colombo Chiara , Conti Claudia , Di Carlo Anna Letizia , Magrini Donata , Mercuri Fulvio , Orazi Noemi , Realini Marco
Published: May 2024

This paper sheds light on the manufacturing processes, techniques, and materials used in the splendid illuminations of the oldest surviving copy of De Balneis Puteolanis, preserved at the Angelica Library in Rome (Ms. 1474). The codex is one of the masterpieces of mid-13th-century Italian-Southern illumination, traditionally referred to as the commission of Manfredi, son of Frederick II. The findings reported in the article result from the interdisciplinary study conducted in 2021–2023 in the framework of “Codex 4D: journey in four dimensions into the manuscript”, a multidisciplinary project involving many competences and dealing with art-historical studies on manuscripts, diagnostic and conservative analyses, scientific dissemination, storytelling, and public engagement. The considerations we present aims at increasing the knowledge of book artefacts while respecting their extraordinary complexity; data from non-invasive diagnostic investigations (X-ray fluorescence, Vis-NIR reflectance and Raman spectroscopies, hyperspectral imaging, and multi-band imaging techniques as ultraviolet, reflectography, and thermography), carried out in situ with portable instruments on the book, have been integrated with observations resulting from the historical-artistic study, and the reading of some ancient treatises on the production and use of the pigments and dyes employed in illumination.
Atrial Fibrillation and Other Cardiovascular Factors and the Risk of Dementia: An Italian Case–Control Study
Authors: Mazzoli Riccardo , Chiari Annalisa , Vitolo Marco , Garuti Caterina , Adani Giorgia , Vinceti Giulia , Zamboni Giovanna , Tondelli Manuela , Galli Chiara , Costa Manuela , Salemme Simone , Boriani Giuseppe , Vinceti Marco , Filippini Tommaso
Published: May 2024

Dementia is a major neurologic syndrome characterized by severe cognitive decline, and it has a detrimental impact on overall physical health, leading to conditions such as frailty, changes in gait, and fall risk. Depending on whether symptoms occur before or after the age of 65, it can be classified as early-onset (EOD) or late-onset (LOD) dementia. The present study is aimed at investigating the role of cardiovascular factors on EOD and LOD risk in an Italian population. Using a case–control study design, EOD and LOD cases were recruited at the Modena Cognitive Neurology Centers in 2016–2019. Controls were recruited among caregivers of all the dementia cases. Information about their demographics, lifestyles, and medical history were collected through a tailored questionnaire. We used the odds ratio (OR) and 95% confidence interval (CI) to estimate the EOD and LOD risk associated with the investigated factors after adjusting for potential confounders. Of the final 146 participants, 58 were diagnosed with EOD, 34 with LOD, and 54 were controls. According to their medical history, atrial fibrillation was associated with increased disease risk (ORs 1.90; 95% CI 0.32–11.28, and 3.64; 95% CI 0.32–41.39 for EOD and LOD, respectively). Dyslipidemia and diabetes showed a positive association with EOD, while the association was negative for LOD. We could not evaluate the association between myocardial infarction and EOD, while increased risk was observed for LOD. No clear association emerged for carotid artery stenosis or valvular heart disease. In this study, despite the limited number of exposed subjects and the high imprecision of the estimates, we found positive associations between cardiovascular disease, particularly dyslipidemia, diabetes, and atrial fibrillation, and EOD.
Correction: Ferguson et al. Soil, Hand, and Body Adherence Measures across Four Beach Areas: Potential Influence on Exposure to Oil Spill Chemicals. Int. J. Environ. Res. Public Health 2020, 17, 4196
Authors: Ferguson Alesia , Kumar Dwivedi Ashok , Ehindero Esther , Adelabu Foluke , Rattler Kyra , Perone Hanna Rose , Montas Larissa , Mena Kristina , Solo-Gabriele Helena
Published: May 2024

In the original publication [...]
Guidance Certification Effect and Governance Supervision Effect of Government Investment Funds
Authors: Xu Sheng , Li Yaoxiong , Manguet Ndinga Durell Esperance
Published: May 2024

The establishment of government investment funds serves as a crucial measure for governments at all levels to leverage their certification role and financial resources in attracting social capital to support enterprise development. This paper empirically examines the guiding certification effect and governance supervision effect of government investment funds on enterprise value enhancement, utilising panel data from listed companies and government investment fund investment event data spanning the period from 2011 to 2021. The research findings reveal that government investment funds significantly enhance the value of recipient enterprises. By leveraging their guidance and certification effects and governance supervision effects, these funds alleviate financing constraints, actively participate in corporate governance, and ultimately enhance corporate value. The impact of government investment funds is negatively moderated by the age and size of the enterprise, indicating that the “invest in early-stage and small businesses” investment strategy yields better results in promoting value enhancement. Furthermore, heterogeneity analysis demonstrates that government investment funds have a more pronounced impact on the value of non-heavily polluting industries, enterprises located in the eastern and southern regions of China, and non-state-owned enterprises. This article expands the research scope of government investment funds at the micro level, providing empirical evidence and theoretical support for optimising government investment funding policies and fostering the development of a modern capital market with distinctive Chinese characteristics.
A Narrative Review of the Roles of Chondromodulin-I (Cnmd) in Adult Cartilage Tissue
Authors: Reyes Alcaraz Viviana , Pattappa Girish , Miura Shigenori , Angele Peter , Blunk Torsten , Rudert Maximilian , Hiraki Yuji , Shukunami Chisa , Docheva Denitsa
Published: May 2024

Articular cartilage is crucial for joint function but its avascularity limits intrinsic repair, leading to conditions like osteoarthritis (OA). Chondromodulin-I (Cnmd) has emerged as a key molecule in cartilage biology, with potential implications for OA therapy. Cnmd is primarily expressed in cartilage and plays an important role in chondrocyte proliferation, cartilage homeostasis, and the blocking of angiogenesis. In vivo and in vitro studies on Cnmd, also suggest an involvement in bone repair and in delaying OA progression. Its downregulation correlates with OA severity, indicating its potential as a therapeutic target. Further research is needed to fully understand the mode of action of Cnmd and its beneficial implications for managing OA. This comprehensive review aims to elucidate the molecular characteristics of Cnmd, from its expression pattern, role in cartilage maintenance, callus formation during bone repair and association with OA.
Ethyl Pyruvate Decreases Collagen Synthesis and Upregulates MMP Activity in Keloid Fibroblasts and Keloid Spheroids
Authors: Baek Wooyeol , Park Seonghyuk , Lee Youngdae , Roh Hyun , Yun Chae-Ok , Roh Tai Suk , Lee Won Jai
Published: May 2024

Keloids, marked by abnormal cellular proliferation and excessive extracellular matrix (ECM) accumulation, pose significant therapeutic challenges. Ethyl pyruvate (EP), an inhibitor of the high-mobility group box 1 (HMGB1) and TGF-β1 pathways, has emerged as a potential anti-fibrotic agent. Our research evaluated EP’s effects on keloid fibroblast (KF) proliferation and ECM production, employing both in vitro cell cultures and ex vivo patient-derived keloid spheroids. We also analyzed the expression levels of ECM components in keloid tissue spheroids treated with EP through immunohistochemistry. Findings revealed that EP treatment impedes the nuclear translocation of HMGB1 and diminishes KF proliferation. Additionally, EP significantly lowered mRNA and protein levels of collagen I and III by attenuating TGF-β1 and pSmad2/3 complex expression in both human dermal fibroblasts and KFs. Moreover, metalloproteinase I (MMP-1) and MMP-3 mRNA levels saw a notable increase following EP administration. In keloid spheroids, EP induced a dose-dependent reduction in ECM component expression. Immunohistochemical and western blot analyses confirmed significant declines in collagen I, collagen III, fibronectin, elastin, TGF-β, AKT, and ERK 1/2 expression levels. These outcomes underscore EP’s antifibrotic potential, suggesting its viability as a therapeutic approach for keloids.
The Relationship between Circadian Rhythm and Cancer Disease
Authors: Munteanu Camelia , Turti Sabina , Achim Larisa , Muresan Raluca , Souca Marius , Prifti Eftimia , Mârza Sorin Marian , Papuc Ionel
Published: May 2024

The circadian clock regulates biological cycles across species and is crucial for physiological activities and biochemical reactions, including cancer onset and development. The interplay between the circadian rhythm and cancer involves regulating cell division, DNA repair, immune function, hormonal balance, and the potential for chronotherapy. This highlights the importance of maintaining a healthy circadian rhythm for cancer prevention and treatment. This article investigates the complex relationship between the circadian rhythm and cancer, exploring how disruptions to the internal clock may contribute to tumorigenesis and influence cancer progression. Numerous databases are utilized to conduct searches for articles, such as NCBI, MEDLINE, and Scopus. The keywords used throughout the academic archives are “circadian rhythm”, ”cancer”, and ”circadian clock”. Maintaining a healthy circadian cycle involves prioritizing healthy sleep habits and minimizing disruptions, such as consistent sleep schedules, reduced artificial light exposure, and meal timing adjustments. Dysregulation of the circadian clock gene and cell cycle can cause tumor growth, leading to the need to regulate the circadian cycle for better treatment outcomes. The circadian clock components significantly impact cellular responses to DNA damage, influencing cancer development. Understanding the circadian rhythm’s role in tumor diseases and their therapeutic targets is essential for treating and preventing cancer. Disruptions to the circadian rhythm can promote abnormal cell development and tumor metastasis, potentially due to immune system imbalances and hormonal fluctuations.
Magnetic Nanoparticles for Biomedical and Imaging Applications
Authors: Konnova Svetlana , Rozhina Elvira
Published: May 2024

Magnetic nanoparticles (MNPs) are a class of nanomaterials composed of metals such as cobalt, nickel, and iron with paramagnetic, ferromagnetic, or superparamagnetic properties [...]
Genome-Wide Identification and Expression Analysis of the High-Mobility Group B (HMGB) Gene Family in Plant Response to Abiotic Stress in Tomato
Authors: Zheng Jinhui , Tang Huimeng , Wang Jianquan , Liu Yue , Ge Lianjing , Liu Guobiao , Shi Qinghua , Zhang Yan
Published: May 2024

High-mobility group B (HMGB) proteins are a class of non-histone proteins associated with eukaryotic chromatin and are known to regulate a variety of biological processes in plants. However, the functions of HMGB genes in tomato (Solanum lycopersicum) remain largely unexplored. Here, we identified 11 members of the HMGB family in tomato using BLAST. We employed genome-wide identification, gene structure analysis, domain conservation analysis, cis-acting element analysis, collinearity analysis, and qRT-PCR-based expression analysis to study these 11 genes. These genes were categorized into four groups based on their unique protein domain structures. Despite their structural diversity, all members contain the HMG-box domain, a characteristic feature of the HMG superfamily. Syntenic analysis suggested that tomato SlHMGBs have close evolutionary relationships with their homologs in other dicots. The promoter regions of SlHMGBs are enriched with numerous cis-elements related to plant growth and development, phytohormone responsiveness, and stress responsiveness. Furthermore, SlHMGB members exhibited distinct tissue-specific expression profiles, suggesting their potential roles in regulating various aspects of plant growth and development. Most SlHMGB genes respond to a variety of abiotic stresses, including salt, drought, heat, and cold. For instance, SlHMGB2 and SlHMGB4 showed positive responses to salt, drought, and cold stresses. SlHMGB1, SlHMGB3, and SlHMGB8 were involved in responses to two types of stress: SlHMGB1 responded to drought and heat, while SlHMGB3 and SlHMGB8 responded to salt and heat. SlHMGB6 and SlHMGB11 were solely regulated by drought and heat stress, respectively. Under various treatment conditions, the number of up-regulated genes significantly outnumbered the down-regulated genes, implying that the SlHMGB family may play a crucial role in mitigating abiotic stress in tomato. These findings lay a foundation for further dissecting the precise roles of SlHMGB genes.
N-Acetylgalactosamine-4-sulfatase (Arylsulfatase B) Regulates PD-L1 Expression in Melanoma by an HDAC3-Mediated Epigenetic Mechanism
Authors: Bhattacharyya Sumit , O-Sullivan InSug , Tobacman Joanne K.
Published: May 2024

The effects of the enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B, ARSB), which removes the 4-sulfate group at the non-reducing end of chondroitin 4-sulfate, on the expression of PD-L1 were determined, and the underlying mechanism of PD-L1 expression was elucidated. Initial experiments in human melanoma cells (A375) showed that PD-L1 expression increased from 357 ± 31 to 796 ± 50 pg/mg protein (p < 10−11) when ARSB was silenced in A375 cells. In subcutaneous B16F10 murine melanomas, PD-L1 declined from 1227 ± 189 to 583 ± 110 pg/mg protein (p = 1.67 × 10−7), a decline of 52%, following treatment with exogenous, bioactive recombinant ARSB. This decline occurred in association with reduced tumor growth and prolongation of survival, as previously reported. The mechanism of regulation of PD-L1 expression by ARSB is attributed to ARSB-mediated alteration in chondroitin 4-sulfation, leading to changes in free galectin-3, c-Jun nuclear localization, HDAC3 expression, and effects of acetyl-H3 on the PD-L1 promoter. These findings indicate that changes in ARSB contribute to the expression of PD-L1 in melanoma and can thereby affect the immune checkpoint response. Exogenous ARSB acted on melanoma cells and normal melanocytes through the IGF2 receptor. The decline in PD-L1 expression by exogenous ARSB may contribute to the impact of ARSB on melanoma progression.
Adenosine in Interventional Cardiology: Physiopathologic and Pharmacologic Effects in Coronary Artery Disease
Authors: Marchi Enrico , Muraca Iacopo , Berteotti Martina , Gori Anna Maria , Valenti Renato , Marcucci Rossella
Published: May 2024

This review article focuses on the role of adenosine in coronary artery disease (CAD) diagnosis and treatment. Adenosine, an endogenous purine nucleoside, plays crucial roles in cardiovascular physiology and pathology. Its release and effects, mediated by specific receptors, influence vasomotor function, blood pressure regulation, heart rate, and platelet activity. Adenosine therapeutic effects include treatment of the no-reflow phenomenon and paroxysmal supraventricular tachycardia. The production of adenosine involves complex cellular pathways, with extracellular and intracellular synthesis mechanisms. Adenosine’s rapid metabolism underscores its short half-life and physiological turnover. Furthermore, adenosine’s involvement in side effects of antiplatelet therapy, particularly ticagrelor and cangrelor, highlights its clinical significance. Moreover, adenosine serves as a valuable tool in CAD diagnosis, aiding stress testing modalities and guiding intracoronary physiological assessments. Its use in assessing epicardial stenosis and microvascular dysfunction is pivotal for treatment decisions. Overall, understanding adenosine’s mechanisms and clinical implications is essential for optimizing CAD management strategies, encompassing both therapeutic interventions and diagnostic approaches.
ECRG2/SPINK7 Tumor Suppressor as Modulator of DNA Damage Response
Authors: Patel Harsh , Sheikh M. Saeed , Huang Ying
Published: May 2024

Esophageal Cancer-Related Gene 2 (ECRG2), also known as Serine Peptidase Inhibitor Kazal type 7 (SPINK7), is a novel tumor suppressor gene from the SPINK family of genes that exhibits anticancer potential. ECRG2 was originally identified during efforts to discover genes involved in esophageal tumorigenesis. ECRG2 was one of those genes whose expression was absent or reduced in primary human esophageal cancers. Additionally, absent or reduced ECRG2 expression was also noted in several other types of human malignancies. ECRG2 missense mutations were identified in various primary human cancers. It was reported that a cancer-derived ECRG2 mutant (valine to glutamic acid at position 30) failed to induce cell death and caspase activation triggered by DNA-damaging anticancer drugs. Furthermore, ECRG2 suppressed cancer cell proliferation in cultured cells and grafted tumors in animals and inhibited cancer cell migration/invasion and metastasis. ECRG2 also was identified as a negative regulator of Hu-antigen R (HuR), an oncogenic RNA-binding protein that is known to regulate mRNA stability and the expression of transcripts corresponding to many cancer-related genes. ECRG2 function is important also for the regulation of inflammatory responses and the maintenance of epithelial barrier integrity in the esophagus. More recently, ECRG2 was discovered as one of the newest members of the pro-apoptotic transcriptional targets of p53. Two p53-binding sites (BS-1 and BS-2) were found within the proximal region of the ECRG2 gene promoter; the treatment of DNA-damaging agents in cancer cells significantly increased p53 binding to the ECRG2 promoter and triggered a strong ECRG2 promoter induction following DNA damage. Further, the genetic depletion of ECRG2 expression significantly impeded apoptotic cell death induced by DNA damage and wild-type p53 in cancer cells. These findings suggest that the loss of ECRG2 expression, commonly observed in human cancers, could play important roles in conferring anticancer drug resistance in human cancers. Thus, ECRG2 is a novel regulator in DNA damage-induced cell death that may also be a potential target for anticancer therapeutics.
Genetic Mutations and Mitochondrial Redox Signaling as Modulating Factors in Hypertrophic Cardiomyopathy: A Scoping Review
Authors: Menezes Junior Antonio da Silva , França-e-Silva Ana Luísa Guedes de , Oliveira Henrique Lima de , Lima Khissya Beatryz Alves de , Porto Iane de Oliveira Pires , Pedroso Thays Millena Alves , Silva Daniela de Melo e , Freitas Aguinaldo F.
Published: May 2024

Hypertrophic cardiomyopathy (HCM) is a heart condition characterized by cellular and metabolic dysfunction, with mitochondrial dysfunction playing a crucial role. Although the direct relationship between genetic mutations and mitochondrial dysfunction remains unclear, targeting mitochondrial dysfunction presents promising opportunities for treatment, as there are currently no effective treatments available for HCM. This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews guidelines. Searches were conducted in databases such as PubMed, Embase, and Scopus up to September 2023 using “MESH terms”. Bibliographic references from pertinent articles were also included. Hypertrophic cardiomyopathy (HCM) is influenced by ionic homeostasis, cardiac tissue remodeling, metabolic balance, genetic mutations, reactive oxygen species regulation, and mitochondrial dysfunction. The latter is a common factor regardless of the cause and is linked to intracellular calcium handling, energetic and oxidative stress, and HCM-induced hypertrophy. Hypertrophic cardiomyopathy treatments focus on symptom management and complication prevention. Targeted therapeutic approaches, such as improving mitochondrial bioenergetics, are being explored. This includes coenzyme Q and elamipretide therapies and metabolic strategies like therapeutic ketosis. Understanding the biomolecular, genetic, and mitochondrial mechanisms underlying HCM is crucial for developing new therapeutic modalities.
Comparison of the Effects of Essential Oils from Cannabis sativa and Cannabis indica on Selected Bacteria, Rumen Fermentation, and Methane Production—In Vitro Study
Authors: Tabiś Aleksandra , Szumny Antoni , Bania Jacek , Pacyga Katarzyna , Lewandowska Kamila , Kupczyński Robert
Published: May 2024

This study aimed to evaluate the effects of essential oils (EOs) extracted from Cannabis sativa L. and Cannabis indica Lam. on in vitro ruminal fermentation characteristics, selected rumen microbial populations, and methane production. GC-MS analyses allowed us to identify 89 compounds in both EOs. It was found that E-β-caryophyllene predominated in C. sativa (18.4%) and C. indica (24.1%). An in vitro (Ankom) test was performed to analyse the control and monensin groups, as well as the 50 µL or 100 µL EOs. The samples for volatile fatty acids (VFAs), lactate, and microbiological analysis were taken before incubation and after 6 and 24 h. The application of EOs of C. indica resulted in an increase in the total VFAs of acetate and propionate after 6 h of incubation. The applied EOs had a greater impact on the reduction in methane production after 6 h, but no apparent effect was noted after 24 h. Lower concentrations of C. sativa and C. indica had a more pronounced effect on Lactobacillus spp. and Buryrivibrio spp. than monensin. The presented findings suggest that C. sativa and C. indica supplementation can modify ruminal fermentation, the concentrations of specific volatile fatty acids, and methane production.
Applications of Stem Cell-Derived Extracellular Vesicles in Nerve Regeneration
Authors: Yavuz Burcak , Mutlu Esra Cansever , Ahmed Zubair , Ben-Nissan Besim , Stamboulis Artemis
Published: May 2024

Extracellular vesicles (EVs), including exosomes, microvesicles, and other lipid vesicles derived from cells, play a pivotal role in intercellular communication by transferring information between cells. EVs secreted by progenitor and stem cells have been associated with the therapeutic effects observed in cell-based therapies, and they also contribute to tissue regeneration following injury, such as in orthopaedic surgery cases. This review explores the involvement of EVs in nerve regeneration, their potential as drug carriers, and their significance in stem cell research and cell-free therapies. It underscores the importance of bioengineers comprehending and manipulating EV activity to optimize the efficacy of tissue engineering and regenerative therapies.
Nutraceuticals and Functional Foods: A Comprehensive Review of Their Role in Bone Health
Authors: Faienza Maria Felicia , Giardinelli Silvia , Annicchiarico Alessia , Chiarito Mariangela , Barile Barbara , Corbo Filomena , Brunetti Giacomina
Published: May 2024

Bone health is the result of a tightly regulated balance between bone modeling and bone remodeling, and alterations of these processes have been observed in several diseases both in adult and pediatric populations. The imbalance in bone remodeling can ultimately lead to osteoporosis, which is most often associated with aging, but contributing factors can already act during the developmental age, when over a third of bone mass is accumulated. The maintenance of an adequate bone mass is influenced by genetic and environmental factors, such as physical activity and diet, and particularly by an adequate intake of calcium and vitamin D. In addition, it has been claimed that the integration of specific nutraceuticals such as resveratrol, anthocyanins, isoflavones, lycopene, curcumin, lutein, and β-carotene and the intake of bioactive compounds from the diet such as honey, tea, dried plums, blueberry, and olive oil can be efficient strategies for bone loss prevention. Nutraceuticals and functional foods are largely used to provide medical or health benefits, but there is an urge to determine which products have adequate clinical evidence and a strong safety profile. The aim of this review is to explore the scientific and clinical evidence of the positive role of nutraceuticals and functional food in bone health, focusing both on molecular mechanisms and on real-world studies.
Advancing Renal Amyloidosis Care: The Role of Modern Diagnostic Techniques with the Potential of Enhancing Patient Outcomes
Authors: Delrue Charlotte , Dendooven Amélie , Vandendriessche Annelore , Speeckaert Reinhart , De Bruyne Sander , Speeckaert Marijn M.
Published: May 2024

Renal amyloidosis is a set of complex disorders characterized by the deposition of amyloid proteins in the kidneys, which causes gradual organ damage and potential kidney failure. Recent developments in diagnostic methods, particularly mass spectrometry and proteome profiling, have greatly improved the accuracy of amyloid typing, which is critical for disease management. These technologies provide extensive insights into the specific proteins involved, allowing for more targeted treatment approaches and better patient results. Despite these advances, problems remain, owing to the heterogeneous composition of amyloid proteins and the varying efficacy of treatments based on amyloid type. Access to sophisticated diagnostics and therapy varies greatly, highlighting the global difference in renal amyloidosis management. Future research is needed to investigate next-generation sequencing and gene-editing technologies, like clustered regularly interspaced short palindromic repeats (CRISPR), which promise more profound insights into the genetic basis of amyloidosis.
Chordoma: Genetics and Contemporary Management
Authors: Desai Rupen , Pelargos Panayiotis E. , Dunn Ian F.
Published: May 2024

Chordomas, arising from notochord remnants, are rare neoplasms with aggressive growth patterns despite their histologically low-grade nature. This review explores their embryological origins, molecular markers like brachyury, and genetic alterations driving pathogenesis. Diagnosis relies on advanced imaging and biopsy confirmation due to overlapping features with chondrosarcoma. The WHO classification distinguishes conventional, dedifferentiated, and poorly differentiated chordomas, each with distinct prognostic implications. Recent genomic analyses uncovered recurrent mutations in PI3K signaling pathways and chromatin remodeling genes, informing prognostic models. Surgery remains the cornerstone of treatment, though adjuvant radiation complements surgical resection. Although chordomas are generally considered refractory to medical therapy, emerging targeted molecular strategies show potential promise in ongoing trials. This review aims to provide a concise yet comprehensive overview of chordomas, guiding clinicians in diagnosis, treatment, and prognostication for improved patient outcomes.
The Transcriptional Regulator TfmR Directly Regulates Two Pathogenic Pathways in Xanthomonas oryzae pv. oryzicola
Authors: Chang Zheng , Ma Zengfeng , Su Qian , Xia Xinqi , Ye Wenxin , Li Ruifang , Lu Guangtao
Published: May 2024

Xanthomonas oryzae pv. oryzicola (Xoc) is a notorious plant pathogen. Like most bacterial pathogens, Xoc has evolved a complex regulatory network to modulate the expression of various genes related to pathogenicity. Here, we have identified TfmR, a transcriptional regulator belonging to the TetR family, as a key player in the virulence mechanisms of this phytopathogenic bacterium. We have demonstrated genetically that tfmR is involved in the hypersensitive response (HR), pathogenicity, motility and extracellular polysaccharide production of this phytopathogenic bacterium. Our investigations extended to exploring TfmR’s interaction with RpfG and HrpX, two prominent virulence regulators in Xanthomonas species. We found that TfmR directly binds to the promoter region of RpfG, thereby positively regulating its expression. Notably, constitutive expression of RpfG partly reinstates the pathogenicity compromised by TfmR-deletion mutants. Furthermore, our studies revealed that TfmR also exerts direct positive regulation on the expression of the T3SS regulator HrpX. Similar to RpfG, sustained expression of HrpX partially restores the pathogenicity of TfmR-deletion mutants. These findings underscore TfmR’s multifaceted role as a central regulator governing key virulence pathways in Xoc. Importantly, our research sheds light on the intricate molecular mechanisms underlying the regulation of pathogenicity in this plant pathogen.
Different Drug Mobilities in Hydrophobic Cavities of Host–Guest Complexes between β-Cyclodextrin and 5-Fluorouracil at Different Stoichiometries: A Molecular Dynamics Study in Water
Authors: Raffaini Giuseppina , Elli Stefano , Catauro Michelina , D’Angelo Antonio
Published: May 2024

Cyclodextrins (CDs) are cyclic oligosaccharides able to form noncovalent water-soluble complexes useful in many different applications for the solubilization, delivery, and greater bioavailability of hydrophobic drugs. The complexation of 5-fluorouracil (5-FU) with natural or synthetic cyclodextrins permits the solubilization of this poorly soluble anticancer drug. In this theoretical work, the complexes between β-CD and 5-FU are investigated using molecular mechanics (MM) and molecular dynamics (MD) simulations in water. The inclusion complexes are formed thanks to the favorable intermolecular interactions between β-CD and 5-FU. Both 1:1 and 1:2 β-CD/5-FU stoichiometries are investigated, providing insight into their interaction geometries and stability over time in water. In the 1:2 β-CD/5-FU complexes, the intermolecular interactions affect the drug’s mobility, suggesting a two-step release mechanism: a fast release for the more exposed and hydrated drug molecule, with greater freedom of movement near the β-CD rims, and a slow one for the less-hydrated and well-encapsulated and confined drug. MD simulations study the intermolecular interactions between drugs and specific carriers at the atomistic level, suggesting a possible release mechanism and highlighting the role of the impact of the drug concentration on the kinetics process in water. A comparison with experimental data in the literature provides further insights.
Hyaluronic Acid/Ellagic Acid as Materials for Potential Medical Application
Authors: Kaczmarek-Szczepańska Beata , Kleszczyński Konrad , Zasada Lidia , Chmielniak Dorota , Hollerung Mara Barbara , Dembińska Katarzyna , Pałubicka Krystyna , Steinbrink Kerstin , Swiontek Brzezinska Maria , Grabska-Zielińska Sylwia
Published: May 2024

The aim of this work was to develop and characterize a thin films composed of hyaluronic acid/ellagic acid for potential medical application. Its principal novelty, distinct from the prior literature in terms of hyaluronic acid films supplemented with phenolic acids, resides in the predominant incorporation of ellagic acid—a distinguished compound—as the primary constituent of the films. Herein, ellagic acid was dissolved in two different solvents, i.e., acetic acid (AcOH) or sodium hydroxide (NaOH), and the surface properties of the resultant films were assessed using atomic force microscopy and contact angle measurements. Additionally, various physicochemical parameters were evaluated including moisture content, antioxidant activity, and release of ellagic acid in phosphate buffered saline. Furthermore, the evaluation of films’ biocompatibility was conducted using human epidermal keratinocytes, dermal fibroblasts, and human amelanotic melanoma cells (A375 and G361), and the antimicrobial activity was elucidated accordingly against Staphylococcus aureus ATCC 6538 and Pseudomonas aeruginosa ATCC 15442. Our results showed that the films exhibited prominent antibacterial properties particularly against Staphylococcus aureus, with the 80HA/20EA/AcOH film indicating the strong biocidal activity against this strain leading to a significant reduction in viable cells. Comparatively, the 50HA/50EA/AcOH film also displayed biocidal activity against Staphylococcus aureus. This experimental approach could be a promising technique for future applications in regenerative dermatology or novel strategies in terms of bioengineering.
Influence of Fungicide Application on Rhizosphere Microbiota Structure and Microbial Secreted Enzymes in Diverse Cannabinoid-Rich Hemp Cultivars
Authors: Xu Junhuan , Knight Tyson , Boone Donchel , Saleem Muhammad , Finley Sheree J. , Gauthier Nicole , Ayariga Joseph A. , Akinrinlola Rufus , Pulkoski Melissa , Britt Kadie , Tolosa Tigist , Rosado-Rivera Yara I. , Iddrisu Ibrahim , Thweatt Ivy , Li Ting , Zebelo Simon , Burrack Hannah , Thiessen Lindsey , Hansen Zachariah , Bernard Ernest , Kuhar Thomas , Samuel-Foo Michelle , Ajayi Olufemi S.
Published: May 2024

Microbes and enzymes play essential roles in soil and plant rhizosphere ecosystem functioning. However, fungicides and plant root secretions may impact the diversity and abundance of microbiota structure and enzymatic activities in the plant rhizosphere. In this study, we analyzed soil samples from the rhizosphere of four cannabinoid-rich hemp (Cannabis sativa) cultivars (Otto II, BaOx, Cherry Citrus, and Wife) subjected to three different treatments (natural infection, fungal inoculation, and fungicide treatment). DNA was extracted from the soil samples, 16S rDNA was sequenced, and data were analyzed for diversity and abundance among different fungicide treatments and hemp cultivars. Fungicide treatment significantly impacted the diversity and abundance of the hemp rhizosphere microbiota structure, and it substantially increased the abundance of the phyla Archaea and Rokubacteria. However, the abundances of the phyla Pseudomonadota and Gemmatimonadetes were substantially decreased in treatments with fungicides compared to those without fungicides in the four hemp cultivars. In addition, the diversity and abundance of the rhizosphere microbiota structure were influenced by hemp cultivars. The influence of Cherry Citrus on the diversity and abundance of the hemp rhizosphere microbiota structure was less compared to the other three hemp cultivars (Otto II, BaOx, and Wife). Moreover, fungicide treatment affected enzymatic activities in the hemp rhizosphere. The application of fungicides significantly decreased enzyme abundance in the rhizosphere of all four hemp cultivars. Enzymes such as dehydrogenase, dioxygenase, hydrolase, transferase, oxidase, carboxylase, and peptidase significantly decreased in all the four hemp rhizosphere treated with fungicides compared to those not treated. These enzymes may be involved in the function of metabolizing organic matter and degrading xenobiotics. The ecological significance of these findings lies in the recognition that fungicides impact enzymes, microbiota structure, and the overall ecosystem within the hemp rhizosphere.