bluuebunny/crossref_metadata_2025 huggingface dataset:
GSK3-Driven Modulation of Inflammation and Tissue Integrity in the Animal Model
Authors: Kühl Friederike , Brand Korbinian , Lichtinghagen Ralf , Huber René
Published: July 2024

Nowadays, GSK3 is accepted as an enzyme strongly involved in the regulation of inflammation by balancing the pro- and anti-inflammatory responses of cells and organisms, thus influencing the initiation, progression, and resolution of inflammatory processes at multiple levels. Disturbances within its broad functional scope, either intrinsically or extrinsically induced, harbor the risk of profound disruptions to the regular course of the immune response, including the formation of severe inflammation-related diseases. Therefore, this review aims at summarizing and contextualizing the current knowledge derived from animal models to further shape our understanding of GSK3α and β and their roles in the inflammatory process and the occurrence of tissue/organ damage. Following a short recapitulation of structure, function, and regulation of GSK3, we will focus on the lessons learned from GSK3α/β knock-out and knock-in/overexpression models, both conventional and conditional, as well as a variety of (predominantly rodent) disease models reflecting defined pathologic conditions with a significant proportion of inflammation and inflammation-related tissue injury. In summary, the literature suggests that GSK3 acts as a crucial switch driving pro-inflammatory and destructive processes and thus contributes significantly to the pathogenesis of inflammation-associated diseases.
LncRNA PTENP1/miR-21/PTEN Axis Modulates EMT and Drug Resistance in Cancer: Dynamic Boolean Modeling for Cell Fates in DNA Damage Response
Authors: Gupta Shantanu , Silveira Daner A. , Lorenzoni Pedro R. , Mombach Jose Carlos M. , Hashimoto Ronaldo F.
Published: July 2024

It is well established that microRNA-21 (miR-21) targets phosphatase and tensin homolog (PTEN), facilitating epithelial-to-mesenchymal transition (EMT) and drug resistance in cancer. Recent evidence indicates that PTEN activates its pseudogene-derived long non-coding RNA, PTENP1, which in turn inhibits miR-21. However, the dynamics of PTEN, miR-21, and PTENP1 in the DNA damage response (DDR) remain unclear. Thus, we propose a dynamic Boolean network model by integrating the published literature from various cancers. Our model shows good agreement with the experimental findings from breast cancer, hepatocellular carcinoma (HCC), and oral squamous cell carcinoma (OSCC), elucidating how DDR activation transitions from the intra-S phase to the G2 checkpoint, leading to a cascade of cellular responses such as cell cycle arrest, senescence, autophagy, apoptosis, drug resistance, and EMT. Model validation underscores the roles of PTENP1, miR-21, and PTEN in modulating EMT and drug resistance. Furthermore, our analysis reveals nine novel feedback loops, eight positive and one negative, mediated by PTEN and implicated in DDR cell fate determination, including pathways related to drug resistance and EMT. Our work presents a comprehensive framework for investigating cellular responses following DDR, underscoring the therapeutic potential of targeting PTEN, miR-21, and PTENP1 in cancer treatment.
Studying Biomolecular Protein Complexes via Origami and 3D-Printed Models
Authors: Azulay Hay , Benyunes Inbar , Elber Gershon , Qvit Nir
Published: July 2024

Living organisms are constructed from proteins that assemble into biomolecular complexes, each with a unique shape and function. Our knowledge about the structure–activity relationship of these complexes is still limited, mainly because of their small size, complex structure, fast processes, and changing environment. Furthermore, the constraints of current microscopic tools and the difficulty in applying molecular dynamic simulations to capture the dynamic response of biomolecular complexes and long-term phenomena call for new supplementary tools and approaches that can help bridge this gap. In this paper, we present an approach to comparing biomolecular and origami hierarchical structures and apply it to comparing bacterial microcompartments (BMCs) with spiral-based origami models. Our first analysis compares proteins that assemble the BMC with an origami model called “flasher”, which is the unit cell of an assembled origami model. Then, the BMC structure is compared with the assembled origami model and based on the similarity, a physical scaled-up origami model, which is analogous to the BMC, is constructed. The origami model is translated into a computer-aided design model and manufactured via 3D-printing technology. Finite element analysis and physical experiments of the origami model and 3D-printed parts reveal trends in the mechanical response of the icosahedron, which is constructed from tiled-chiral elements. The chiral elements rotate as the icosahedron expands and we deduce that it allows the BMC to open gates for transmembrane passage of materials.
Study of microRNAs in Gingival Crevicular Fluid as Periodontal Diseases Biomarkers: Systematic Review
Authors: Cosín-Villanueva María , Almiñana-Pastor Pedro J. , García-Giménez Jose Luis , López-Roldán Andrés
Published: July 2024

Aim: The aim of this review was to identify the microRNAs (miRNAs) present in gingival crevicular fluid (GCF) that can be used as biomarkers for the diagnosis of periodontal diseases, and to determine which of them has a higher diagnostic yield for periodontitis. Methods: The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (reference number CRD42024544648). The Pubmed, Scopus, Cochrane Library, Embase, Web of Science, and Google Scholar databases were searched for clinical studies conducted in humans investigating periodontal diseases and miRNAs in GCF. The methodological quality of the articles was measured with the Newcastle–Ottawa Scale. Results: A total of 3222 references were identified in the initial literature search, and 16 articles were finally included in the review. The design of the studies was heterogeneous, which prevented a meta-analysis of the data. Most of the studies compared miRNA expression levels between patients with periodontitis and healthy controls. The most widely researched miRNA in periodontal diseases was miR-200b-3p and miR-146a. Conclusions: the miRNAs most studied are miR-146a, miR-200b, miR-223, miR-23a, and miR-203, and all of them except miR-203 have an acceptable diagnostic plausibility for periodontitis.
Genetic Mutations Associated With TNFAIP3 (A20) Haploinsufficiency and Their Impact on Inflammatory Diseases
Authors: Bagyinszky Eva , An Seong Soo A.
Published: July 2024

TNF-α-induced protein 3 (TNFAIP3), commonly referred to as A20, is an integral part of the ubiquitin-editing complex that significantly influences immune regulation, apoptosis, and the initiation of diverse immune responses. The A20 protein is characterized by an N-terminal ovarian tumor (OTU) domain and a series of seven zinc finger (ZNF) domains. Mutations in the TNFAIP3 gene are implicated in various immune-related diseases, such as Behçet’s disease, polyarticular juvenile idiopathic arthritis, autoimmune thyroiditis, autoimmune hepatitis, and rheumatoid arthritis. These mutations can lead to a spectrum of symptoms, including, but not limited to, recurrent fever, ulcers, rashes, musculoskeletal and gastrointestinal dysfunctions, cardiovascular issues, and respiratory infections. The majority of these mutations are either nonsense (STOP codon) or frameshift mutations, which are typically associated with immune dysfunctions. Nonetheless, missense mutations have also been identified as contributors to these conditions. These genetic alterations may interfere with several biological pathways, notably abnormal NF-κB signaling and dysregulated ubiquitination. Currently, there is no definitive treatment for A20 haploinsufficiency; however, therapeutic strategies can alleviate the symptoms in patients. This review delves into the mutations reported in the TNFAIP3 gene, the clinical progression in affected individuals, potential disease mechanisms, and a brief overview of the available pharmacological interventions for A20 haploinsufficiency. Mandatory genetic testing of the TNFAIP3 gene should be performed in patients diagnosed with autoinflammatory disorders to better understand the genetic underpinnings and guide treatment decisions.
Molecular Basis of Cardiomyopathies in Type 2 Diabetes
Authors: Giardinelli Silvia , Meliota Giovanni , Mentino Donatella , D’Amato Gabriele , Faienza Maria Felicia
Published: July 2024

Diabetic cardiomyopathy (DbCM) is a common complication in individuals with type 2 diabetes mellitus (T2DM), and its exact pathogenesis is still debated. It was hypothesized that chronic hyperglycemia and insulin resistance activate critical cellular pathways that are responsible for numerous functional and anatomical perturbations in the heart. Interstitial inflammation, oxidative stress, myocardial apoptosis, mitochondria dysfunction, defective cardiac metabolism, cardiac remodeling, hypertrophy and fibrosis with consequent impaired contractility are the most common mechanisms implicated. Epigenetic changes also have an emerging role in the regulation of these crucial pathways. The aim of this review was to highlight the increasing knowledge on the molecular mechanisms of DbCM and the new therapies targeting specific pathways.
Venom Ex Machina? Exploring the Potential of Cell-Free Protein Production for Venom Biodiscovery
Authors: Paas Anne , Dresler Josephine , Talmann Lea , Vilcinskas Andreas , Lüddecke Tim
Published: July 2024

Venoms are a complex cocktail of potent biomolecules and are present in many animal lineages. Owed to their translational potential in biomedicine, agriculture and industrial applications, they have been targeted by several biodiscovery programs in the past. That said, many venomous animals are relatively small and deliver minuscule venom yields. Thus, the most commonly employed activity-guided biodiscovery pipeline cannot be applied effectively. Cell-free protein production may represent an attractive tool to produce selected venom components at high speed and without the creation of genetically modified organisms, promising rapid and highly efficient access to biomolecules for bioactivity studies. However, these methods have only sporadically been used in venom research and their potential remains to be established. Here, we explore the ability of a prokaryote-based cell-free system to produce a range of venom toxins of different types and from various source organisms. We show that only a very limited number of toxins could be expressed in small amounts. Paired with known problems to facilitate correct folding, our preliminary investigation underpins that venom-tailored cell-free systems probably need to be developed before this technology can be employed effectively in venom biodiscovery.
A Transcriptomic Analysis of Bottle Gourd-Type Rootstock Roots Identifies Novel Transcription Factors Responsive to Low Root Zone Temperature Stress
Authors: Liu Jinqiu , Zhang Man , Xu Jian , Yao Xiefeng , Lou Lina , Hou Qian , Zhu Lingli , Yang Xingping , Liu Guang , Xu Jinhua
Published: July 2024

The bottle gourd [Lagenaria siceraria (Molina) Standl.] is often utilized as a rootstock for watermelon grafting. This practice effectively mitigates the challenges associated with continuous cropping obstacles in watermelon cultivation. The lower ground temperature has a direct impact on the rootstocks’ root development and nutrient absorption, ultimately leading to slower growth and even the onset of yellowing. However, the mechanisms underlying the bottle gourd’s regulation of root growth in response to low root zone temperature (LRT) remain elusive. Understanding the dynamic response of bottle gourd roots to LRT stress is crucial for advancing research regarding its tolerance to low temperatures. In this study, we compared the physiological traits of bottle gourd roots under control and LRT treatments; root sample transcriptomic profiles were monitored after 0 h, 48 h and 72 h of LRT treatment. LRT stress increased the malondialdehyde (MDA) content, relative electrolyte permeability and reactive oxygen species (ROS) levels, especially H2O2 and O2−. Concurrently, LRT treatment enhanced the activities of antioxidant enzymes like superoxide dismutase (SOD) and peroxidase (POD). RNA-Seq analysis revealed the presence of 2507 and 1326 differentially expressed genes (DEGs) after 48 h and 72 h of LRT treatment, respectively. Notably, 174 and 271 transcription factors (TFs) were identified as DEGs compared to the 0 h control. We utilized quantitative real-time polymerase chain reaction (qRT-PCR) to confirm the expression patterns of DEGs belonging to the WRKY, NAC, bHLH, AP2/ERF and MYB families. Collectively, our study provides a robust foundation for the functional characterization of LRT-responsive TFs in bottle gourd roots. Furthermore, these insights may contribute to the enhancement in cold tolerance in bottle gourd-type rootstocks, thereby advancing molecular breeding efforts.
Correlations between Skin Condition Parameters and Ceramide Profiles in the Stratum Corneum of Healthy Individuals
Authors: Akiyama Fuminari , Takahashi Natsumi , Ueda Yuto , Tada Shizuno , Takeuchi Nobuyuki , Ohno Yusuke , Kihara Akio
Published: July 2024

Ceramides are essential lipids for skin barrier function, and various classes and species exist in the human stratum corneum (SC). To date, the relationship between skin conditions and ceramide composition in healthy individuals has remained largely unclear. In the present study, we measured six skin condition parameters (capacitance, transepidermal water loss, scaliness, roughness, multilayer exfoliation, and corneocyte cell size) for the SC of the cheeks and upper arms of 26 healthy individuals and performed correlation analyses with their SC ceramide profiles, which we measured via liquid chromatography–tandem mass spectrometry. In the cheeks, high levels and/or ratios of two free ceramide classes containing an extra hydroxyl group in the long-chain moiety and a protein-bound ceramide class containing 6-hydroxysphingosine correlated with healthy skin conditions. In contrast, the ratios of two other free ceramide classes, both containing sphingosine, and a protein-bound ceramide class containing 4,14-sphingadiene correlated with unhealthy skin conditions, as did shortening of the carbon chain of the fatty acid portion of two ceramide classes containing non-hydroxy fatty acids. Thus, our findings help to elucidate the relationship between skin conditions and ceramide composition.
Kuwanon C Inhibits Tumor Cell Proliferation and Induces Apoptosis by Targeting Mitochondria and Endoplasmic Reticulum
Authors: Yuan Gangxiang , Qian Peng , Chen Lin , He Ningjia
Published: July 2024

Kuwanon C is a unique flavonoid found in the mulberry family, characterized by two isopentenyl groups. While previous research has focused on various properties of kuwanon C, such as antioxidant, hypoglycemic, antimicrobial, food preservation, skin whitening, and nematode lifespan extension, little attention has been given to its potential role in oncological diseases. In this study, we investigate the antitumor effect of kuwanon C in cervical cancer cells and elucidate its specific mechanism of action. We assessed the antitumor effects of kuwanon C using various experimental techniques, including cell proliferation assay, wound healing assays, EdU 488 proliferation assay, mitochondrial membrane potential assay, ROS level assay, cell cycle, apoptosis analysis, and studies on kuwanon C target sites and molecular docking. The results revealed that kuwanon C significantly impacted the cell cycle progression of HeLa cells, disrupted their mitochondrial membrane potential, and induced a substantial increase in intracellular ROS levels. Moreover, kuwanon C exhibited notable anti-proliferative and pro-apoptotic effects on HeLa cells, surpassing the performance of commonly used antitumor drugs such as paclitaxel and cisplatin. Notably, kuwanon C demonstrated superior efficacy while also being more easily accessible compared to paclitaxel. Our study demonstrates that kuwanon C exerts potent antitumor effects by its interaction with the mitochondrial and endoplasmic reticulum membranes, induces a significant production of ROS, disrupts their normal structure, inhibits cell cycle progression, and stimulates apoptotic signaling pathways, ultimately resulting in the death of HeLa tumor cells. As an isopentenyl compound derived from Morus alba, kuwanon C holds great promise as a potential candidate for the development of effective antitumor drugs.
Targeted Nanocarrier-Based Drug Delivery Strategies for Improving the Therapeutic Efficacy of PARP Inhibitors against Ovarian Cancer
Authors: Gralewska Patrycja , Gajek Arkadiusz , Marczak Agnieszka , Rogalska Aneta
Published: July 2024

The current focus of ovarian cancer (OC) research is the improvement of treatment options through maximising drug effectiveness. OC remains the fifth leading cause of cancer-induced mortality in women worldwide. In recent years, nanotechnology has revolutionised drug delivery systems. Nanoparticles may be utilised as carriers in gene therapy or to overcome the problem of drug resistance in tumours by limiting the number of free drugs in circulation and thereby minimising undesired adverse effects. Cell surface receptors, such as human epidermal growth factor 2 (HER2), folic acid (FA) receptors, CD44 (also referred to as homing cell adhesion molecule, HCAM), and vascular endothelial growth factor (VEGF) are highly expressed in ovarian cancer cells. Generation of active targeting nanoparticles involves modification with ligands that recognise cell surface receptors and thereby promote internalisation by cancer cells. Several poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are currently used for the treatment of high-grade serous ovarian carcinomas (HGSOC) or platinum-sensitive relapsed OC. However, PARP resistance and poor drug bioavailability are common challenges, highlighting the urgent need to develop novel, effective strategies for ovarian cancer treatment. This review evaluates the utility of nanoparticles in ovarian cancer therapy, with a specific focus on targeted approaches and the use of PARPi nanocarriers to optimise treatment outcomes.
An Optimized Peptide Antagonist of CXCR4 Limits Survival of BCR–ABL1-Transformed Cells in Philadelphia-Chromosome-Positive B-Cell Acute Lymphoblastic Leukemia
Authors: Pohl Johanna , Litz Angela , El Ayoubi Omar , Rodríguez-Alfonso Armando , Ständker Ludger , Harms Mirja , Münch Jan , Jumaa Hassan , Datta Moumita
Published: July 2024

Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is characterized by reciprocal chromosomal translocation between chromosome 9 and 22, leading to the expression of constitutively active oncogenic BCR–ABL1 fusion protein. CXC chemokine receptor 4 (CXCR4) is essential for the survival of BCR–ABL1-transformed mouse pre-B cells, as the deletion of CXCR4 induces death in these cells. To investigate whether CXCR4 inhibition also effectively blocks BCR–ABL1-transformed cell growth in vitro, in this study, we explored an array of peptide-based inhibitors of CXCR4. The inhibitors were optimized derivatives of EPI-X4, an endogenous peptide antagonist of CXCR4. We observed that among all the candidates, EPI-X4 JM#170 (referred to as JM#170) effectively induced cell death in BCR–ABL1-transformed mouse B cells but had little effect on untransformed wild-type B cells. Importantly, AMD3100, a small molecule inhibitor of CXCR4, did not show this effect. Treatment with JM#170 induced transient JNK phosphorylation in BCR–ABL1-transformed cells, which in turn activated the intrinsic apoptotic pathway by inducing cJun, Bim, and Bax gene expressions. Combinatorial treatment of JM#170 with ABL1 kinase inhibitor Imatinib exerted a stronger killing effect on BCR–ABL1-transformed cells even at a lower dose of Imatinib. Surprisingly, JM#170 actively killed Sup-B15 cells, a BCR–ABL1+ human ALL cell line, but had no effect on the BCR–ABL1− 697 cell line. This suggests that the inhibitory effect of JM#170 is specific for BCR–ABL1+ ALL. Taken together, JM#170 emerges as a potent novel drug against Ph+ ALL.
Local Injection of Stem Cells Can Be a Potential Strategy to Improve Bladder Dysfunction after Outlet Obstruction in Rats
Authors: Liang Ching-Chung , Shaw Steven W. , Chen Tse-Ching , Lin Yi-Hao , Huang Yung-Hsin , Lee Tsong-Hai
Published: July 2024

This study investigates whether hAFSCs can improve bladder function in partial bladder outlet obstruction (pBOO) rats by targeting specific cellular pathways. Thirty-six female rats were divided into sham and pBOO groups with and without hAFSCs single injection into the bladder wall. Cystometry, inflammation/hypoxia, collagen/fibrosis/gap junction proteins, and smooth muscle myosin/muscarinic receptors were examined at 2 and 6 weeks after pBOO or sham operation. In pBOO bladders, significant increases in peak voiding pressure and residual volume stimulated a significant upregulation of inflammatory and hypoxic factors, TGF-β1 and Smad2/3. Collagen deposition proteins, collagen 1 and 3, were significantly increased, but bladder fibrosis markers, caveolin 1 and 3, were significantly decreased. Gap junction intercellular communication protein, connexin 43, was significantly increased, but the number of caveolae was significantly decreased. Markers for the smooth muscle phenotype, myosin heavy chain 11 and guanylate-dependent protein kinase, as well as M2 muscarinic receptors, were significantly increased in cultured detrusor cells. However, hAFSCs treatment could significantly ameliorate bladder dysfunction by inactivating the TGFβ-Smad signaling pathway, reducing collagen deposition, disrupting gap junctional intercellular communication, and modifying the expressions of smooth muscle myosin and caveolae/caveolin proteins. The results support the potential value of hAFSCs-based treatment of bladder dysfunction in BOO patients.
Identification of Variants of Uncertain Significance in the Genes Associated with Thoracic Aortic Disease in Russian Patients with Nonsyndromic Sporadic Subtypes of the Disorder
Authors: Goncharova Irina A. , Shipulina Sofia A. , Sleptcov Aleksei A. , Zarubin Aleksei A. , Valiakhmetov Nail R. , Panfilov Dmitry S. , Lelik Evgeniya V. , Saushkin Viktor V. , Kozlov Boris N. , Nazarenko Ludmila P. , Nazarenko Maria S.
Published: July 2024

Nonsyndromic sporadic thoracic aortic aneurysm (nssTAA) is characterized by diverse genetic variants that may vary in different populations. Our aim was to identify clinically relevant variants in genes implicated in hereditary aneurysms in Russian patients with nssTAA. Forty-one patients with nssTAA without dissection were analyzed. Using massive parallel sequencing, we searched for variants in exons of 53 known disease-causing genes. Patients were found to have no (likely) pathogenic variants in the genes of hereditary TAA. Six variants of uncertain significance (VUSs) were identified in four (9.8%) patients. Three VUSs [FBN1 c.7841C>T (p.Ala2614Val), COL3A1 c.2498A>T (p.Lys833Ile), and MYH11 c.4993C>T (p.Arg1665Cys)] are located in genes with “definitive” disease association (ClinGen). The remaining variants are in “potentially diagnostic” genes or genes with experimental evidence of disease association [NOTCH1 c.964G>A (p.Val322Met), COL4A5 c.953C>G (p.Pro318Arg), and PLOD3 c.833G>A (p.Gly278Asp)]. Russian patients with nssTAA without dissection examined in this study have ≥1 VUSs in six known genes of hereditary TAA (FBN1, COL3A1, MYH11, NOTCH1, COL4A5, or PLOD3). Experimental studies expanded genetic testing, and clinical examination of patients and first/second-degree relatives may shift VUSs to the pathogenic (benign) category or to a new class of rare “predisposing” low-penetrance variants causing the pathology if combined with other risk factors.
Search for Expression Marker Genes That Reflect the Physiological Conditions of Blossom End Enlargement Occurrence in Cucumber
Authors: Li Rui , Atarashi Runewa , Kharisma Agung Dian , Arofatullah Nur Akbar , Tashiro Yuki , Satitmunnaithum Junjira , Tanabata Sayuri , Yamane Kenji , Sato Tatsuo
Published: July 2024

Blossom end enlargement (BEE) is a postharvest deformation that may be related to the influx of photosynthetic assimilates before harvest. To elucidate the mechanism by which BEE occurs, expression marker genes that indicate the physiological condition of BEE-symptomatic fruit are necessary. First, we discovered that preharvest treatment with a synthetic cytokinin, N-(2-Chloro-4-pyridyl)-N’-phenylurea (CPPU), promoted fruit growth and suppressed BEE occurrence. This suggests that excessive assimilate influx is not a main cause of BEE occurrence. Subsequently, the expression levels of seven sugar-starvation marker genes, CsSEF1, AS, CsFDI1, CsPID, CsFUL1, CsETR1, and CsERF1B, were compared among symptomatic and asymptomatic fruits, combined with and without CPPU treatment. Only CsSEF1 showed a higher expression level in asymptomatic fruits than in symptomatic fruits, regardless of CPPU treatment. This was then tested using fruits stored via the modified-atmosphere packaging technique, which resulted in a lower occurrence of BEE, and the asymptomatic fruits showed a higher CsSEF1 expression level than symptomatic fruits, regardless of the packaging method. CsSEF1 codes a CCCH-type zinc finger protein, and an increase in the expression of CsSEF1 was correlated with a decrease in the fruit respiration rate. Thus, CsSEF1 may be usable as a BEE expression marker gene.
Do Microplastics Have Neurological Implications in Relation to Schizophrenia Zebrafish Models? A Brain Immunohistochemistry, Neurotoxicity Assessment, and Oxidative Stress Analysis
Authors: Savuca Alexandra , Curpan Alexandrina-Stefania , Hritcu Luminita Diana , Buzenchi Proca Teodora Maria , Balmus Ioana-Miruna , Lungu Petru Fabian , Jijie Roxana , Nicoara Mircea Nicusor , Ciobica Alin Stelian , Solcan Gheorghe , Solcan Carmen
Published: July 2024

The effects of exposure to environmental pollutants on neurological processes are of increasing concern due to their potential to induce oxidative stress and neurotoxicity. Considering that many industries are currently using different types of plastics as raw materials, packaging, or distribution pipes, microplastics (MPs) have become one of the biggest threats to the environment and human health. These consequences have led to the need to raise the awareness regarding MPs negative neurological effects and implication in neuropsychiatric pathologies, such as schizophrenia. The study aims to use three zebrafish models of schizophrenia obtained by exposure to ketamine (Ket), methionine (Met), and their combination to investigate the effects of MP exposure on various nervous system structures and the possible interactions with oxidative stress. The results showed that MPs can interact with ketamine and methionine, increasing the severity and frequency of optic tectum lesions, while co-exposure (MP+Met+Ket) resulted in attenuated effects. Regarding oxidative status, we found that all exposure formulations led to oxidative stress, changes in antioxidant defense mechanisms, or compensatory responses to oxidative damage. Met exposure induced structural changes such as necrosis and edema, while paradoxically activating periventricular cell proliferation. Taken together, these findings highlight the complex interplay between environmental pollutants and neurotoxicants in modulating neurotoxicity.
Identification and Expression Analysis of Cytochrome P450 Genes Probably Involved in Triterpenoid Saponins Biosynthesis in Astragalus mongholicus
Authors: Wang Junxiu , Yang Baoping , Zhang Fusheng , Wang Jiaorui , Xue Kunlun , Hussain Chang Babar , Zhang Jianqin , Qin Xuemei
Published: July 2024

Cytochromes P450 (P450s) are one of the largest enzymatic protein families and play critical roles in the synthesis and metabolism of plant secondary metabolites. Astragaloside IV (AS-IV) is one of the primary active components in Astragalus herbs, exhibiting diverse biological activities and pharmacological effects. However, P450s involved in the astragaloside biosynthesis have not been systematically analyzed in Astragalus mongholicus (A. mongholicus). In this study, we identified 209 P450 genes from the genome of A. mongholicus (AmP450s), which were classified into nine clans and 47 families and performed a systematic overview of their physical and chemical properties, phylogeny, gene structures and conserved motifs. Weighted gene co-expression network analysis (WGCNA) revealed that AmP450s are critical in the astragaloside biosynthesis pathway. The expression levels of these AmP450s were verified by quantitative real-time PCR (qRT-PCR) analysis in the root, stem and leaf, showing that most AmP450s are abundant in the root. Additionally, the correlation analysis between gene expressions and AS-IV content showed that twelve AmP450s, especially CYP71A28, CYP71D16 and CYP72A69, may have significant potential in the biosynthesis of astragaloside. This study systematically investigates the P450s of A. mongholicus and offers valuable insights into further exploring the functions of CYP450s in the astragaloside biosynthesis pathway.
Molecular Dynamics Simulations of Effects of Geometric Parameters and Temperature on Mechanical Properties of Single-Walled Carbon Nanotubes
Authors: Najmi Lida , Hu Zhong
Published: July 2024

Carbon nanotubes (CNTs) are considered an advanced form of carbon. They have superior characteristics in terms of mechanical and thermal properties compared to other available fibers and can be used in various applications, such as supercapacitors, sensors, and artificial muscles. The properties of single-walled carbon nanotubes (SWNTs) are significantly affected by geometric parameters such as chirality and aspect ratio, and testing conditions such as temperature and strain rate. In this study, the effects of geometric parameters and temperature on the mechanical properties of SWNTs were studied by molecular dynamics (MD) simulations using the Large-scaled Atomic/Molecular Massively Parallel Simulator (LAMMPS). Based on the second-generation reactive empirical bond order (REBO) potential, SWNTs of different diameters were tested in tension and compression under different strain rates and temperatures to understand their effects on the mechanical behavior of SWNTs. It was observed that the Young’s modulus and the tensile strength decreases with increasing SWNT tube diameter. As the chiral angle increases, the tensile strength increases, while the Young’s modulus decreases. The simulations were repeated at different temperatures of 300 K, 900 K, 1500 K, 2100 K and different strain rates of 1 × 10−3/ps, 0.75 × 10−3/ps, 0.5 × 10−3/ps, and 0.25 × 10−3/ps to investigate the effects of temperature and strain rate, respectively. The results show that the ultimate tensile strength of SWNTs increases with increasing strain rate. It is also seen that when SWNTs were stretched at higher temperatures, they failed at lower stresses and strains. The compressive behavior results indicate that SWNTs tend to buckle under lower stresses and strains than those under tensile stress. The simulation results were validated by and consistent with previous studies. The presented approach can be applied to investigate the properties of other advanced materials.
Oil Spill Mitigation with a Team of Heterogeneous Autonomous Vehicles
Authors: Dias André , Mucha Ana , Santos Tiago , Oliveira Alexandre , Amaral Guilherme , Ferreira Hugo , Martins Alfredo , Almeida José , Silva Eduardo
Published: July 2024

This paper presents the implementation of an innovative solution based on heterogeneous autonomous vehicles to tackle maritime pollution (in particular, oil spills). This solution is based on native microbial consortia with bioremediation capacity, and the adaptation of air and surface autonomous vehicles for in situ release of autochthonous microorganisms (bioaugmentation) and nutrients (biostimulation). By doing so, these systems can be applied as the first line of the response to pollution incidents from several origins that may occur inside ports, around industrial and extraction facilities, or in the open sea during transport activities in a fast, efficient, and low-cost way. The paper describes the work done in the development of a team of autonomous vehicles able to carry as payload, native organisms to naturally degrade oil spills (avoiding the introduction of additional chemical or biological additives), and the development of a multi-robot framework for efficient oil spill mitigation. Field tests have been performed in Portugal and Spain’s harbors, with a simulated oil spill, and the coordinate oil spill task between the autonomous surface vehicle (ASV) ROAZ and the unmanned aerial vehicle (UAV) STORK has been validated.
Identifying the Authenticity of Plantscapes through Classics: A Case Study of Beijing Suburbs in the Qing Dynasty
Authors: Xu Dong , Zhu Junda , Chen Zhiyu , Hu Nan , Wang Peiyan , Li Yunyuan
Published: July 2024

The plantscapes surrounding historical gardens hold significant value, reflecting the natural pristine state as well as demonstrating the cultural attributes of the landscape. This study aims to develop a method for identifying the characteristics of historic plantscapes and to recognize the authenticity of historic landscapes from the perspective of plant elements. Our method combines textual and geospatial data analysis to examine the plant species, their relationships and combinations, and spatial distribution. The case study focuses on the Beijing suburbs during the Qing Dynasty, as documented in A Collection of Past Events in Beijing. We identified 658 plants recorded, encompassing 44 families and 58 genera. These plants were categorized into 7 groups based on the growth type and morphological characteristics, leading to 54 plant relationship outcomes, 107 plant combination scenarios, 5 plant combination categories, and 7 representative plant combinations. Additionally, we mapped the spatial distribution of plants, forming 16 plantscape groups and depicting the spatial kernel density distribution of important plants. We also determined the characteristics of plantscapes in different directions in the suburb. Our findings advocate for respecting the historical development of the plantscape and understanding its evolution, particularly emphasizing the use of high-quality native plants and plant combinations.
Language Attitudes in a Historic Latino Community: The Case of Spanish in Northwest Indiana
Authors: Mendieta Eva
Published: July 2024

Despite the burgeoning Latino population in the Midwest, research on language attitudes in this region remains sparse. This study addresses this gap by examining language attitudes and beliefs towards Spanish in the Northwest Indiana region, one of the oldest Latino immigration gateways in the Midwest. Data collected from a 2018–2019 sociolinguistic survey, involving 236 participants representative of the local Latino community, form the basis of the analysis. The study aims to elucidate attitudes towards various Spanish dialects, particularly the local variety. Findings indicate widespread acceptance of the local Spanish variety, with participants viewing its divergence from Mexican or Puerto Rican Spanish as normal and inevitable. Despite perceptions of linguistic mixing with English, the community’s Spanish is valued as an effective communication tool and cultural asset, including in educational settings. This positive attitude towards a stigmatized linguistic variety suggests a preference for any form of Spanish over none, particularly in situations of low Spanish language maintenance. The study of language attitudes shows that speakers will tend to reproduce in their speech new ways of speaking that they find acceptable. This generalized behavior, in turn, leads toward linguistic change.
What I Can Do with the Right Version of You: The Impact of Narrative Perspective on Reader Immersion, and How (in)Formal Address Pronouns Influence Immersion Reports
Authors: Sánchez Carrasco Patricia , Van Hoften Marjolein , Schoenmakers Gert-Jan
Published: July 2024

Previous research has shown that readers experience stronger immersion while reading first-person narratives than third-person narratives, but whether this difference in processing is time-sensitive remains unclear. We report on a self-paced reading experiment in which French participants read short stories in first and in third person. Additionally, participants were directly addressed with either formal or informal second-person pronouns in the final sentence of the narrative, as well as in a subsequent (off-line) questionnaire soliciting post-story immersion reports. The suitability of a particular pronoun of address depends on the social context, and misplaced use can impact the way in which people perceive and assess a particular situation. We did not find significant differences between reading times with first- or third-person pronouns, but participants reported higher immersion and emotional engagement after reading first-person stories than third-person stories. Moreover, the effect of story perspective on reported immersion only occurred when participants were addressed with formal second-person pronouns. We take these findings as evidence for an effect of first- versus third-person pronouns on immersion via perspective shifts. Moreover, we argue that the effect of being addressed with an unexpected (in this case, informal) pronoun can overrule such an effect, while being addressed with an expected (in this case, formal) pronoun can be conducive of it. This finding highlights the importance of research into the impact of pronouns of address.
Investigating the Impact of Dialogic and Trialogic Interactive Factors on Chinese Advanced L2 learners’ Vocabulary Use in Spoken Contexts
Authors: Wang-Taylor Yixin , Clenton Jon , Ren Yinna
Published: July 2024

The main objective of this study is to investigate how interactive factors affect the vocabulary usage of second language learners in their spoken language. Participants were 24 L1 Chinese undergraduate students of L2 English at an advanced level. L2 learners’ vocabulary use was assessed via tokens, lexical diversity, and frequency-based lexical sophistication. Participants provided speech data in response to seven persuasive speaking tasks across three speaking modes: two monologic, two dialogic, and three trialogic. This study showed that the interactive factor has a varied effect on L2 learners’ vocabulary usage. It positively influences the use of advanced vocabulary but does not affect the total number of words produced or the diversity of words used. Second, of all three speaking modes, the dialogic speaking mode is the best speaking condition to trigger L2 learners’ use of advanced words. Third, the vocabulary employed in dialogues and trialogues can vary due to the inherent disparities between the two modes of speech. Therefore, we propose the use of the dialogic interactive factor and trialogic interactive factor instead of the term “interactive factor” to encompass two specific conditions in which there was a noticeable difference in the performance of L2 learners.
Low-Frequency Raman Spectroscopy on Amorphous Poly(Ether Ether Ketone) (PEEK)
Authors: Numata Tomoko , Ishikawa Naomoto , Shimada Toshihiro , Gordon Keith C. , Yamaguchi Makoto
Published: July 2024

Low-frequency peaks in the Raman spectra of amorphous poly(ether ether ketone) (PEEK) were investigated. An amorphous sample with zero crystallinity, as confirmed by wide-angle X-ray diffraction, was used in this study. In a previous study, two peaks were observed in the low-frequency Raman spectra of the crystallized samples. Among these, the peaks at 135 cm−1 disappeared for the amorphous sample. Meanwhile, for the first time, the peak at 50 cm−1 was observed in the crystallized sample. Similar to the peak at 135 cm−1, the peak at 50 cm−1 disappeared in the amorphous state, and its intensity increased with increasing crystallinity. The origins of the two peaks were associated with the Ph-CO-Ph-type intermolecular vibrational modes in the simulation. This suggests that the Ph-CO-Ph vibrational mode observed in the low-frequency region of PEEK was strongly influenced by the intermolecular order.
An Empirical Analysis of Avoidable Medicare Payments and Medicare Payment Variations
Authors: Ren Ai , Buddensick Matthew , Varghese Jake , Li Qi
Published: July 2024

This study investigates the determinants of average Medicare payments, focusing on the impact of secondary diagnoses, demographic factors, and regional disparities. Our model reveals that major complications and comorbidities (MCCs) significantly increase average Medicare payments compared to less severe complications (CCs), with coefficients of 7674.13 and 1542.67, respectively. Higher percentages of the elderly living in poverty correlate with increased payments, highlighting the influence of social determinants on healthcare costs. Demographic analysis shows that counties with higher populations of Black, Hispanic, Asian, or other races receive higher Medicare payments, indicating potential racial disparities in healthcare access and quality. Political affiliation also plays a role, with Democrat-voting counties incurring higher Medicare costs. Surprisingly, larger populations served correlate with decreased payments, possibly due to cost-containment programs like Medicare’s Competitive Bidding. State-level analysis reveals significant regional variations, with states like Oregon and Wyoming showing higher payments, while Mississippi and Georgia have the lowest. Our findings underscore the complexity of Medicare funding and the need for targeted policy interventions to address health disparities and ensure sustainable healthcare delivery.
Hybrid Quantum Neural Network Approaches to Protein–Ligand Binding Affinity Prediction
Authors: Avramouli Maria , Savvas Ilias K. , Vasilaki Anna , Tsipourlianos Andreas , Garani Georgia
Published: July 2024

Drug repositioning is a less expensive and time-consuming method than the traditional method of drug discovery. It is a strategy for identifying new uses for approved or investigational drugs that are outside the scope of the original medical indication. A key strategy in repositioning approved or investigational drugs is determining the binding affinity of these drugs to target proteins. The large increase in available experimental data has helped deep learning methods to demonstrate superior performance compared to conventional prediction and other traditional computational methods in precise binding affinity prediction. However, these methods are complex and time-consuming, presenting a significant barrier to their development and practical application. In this context, quantum computing (QC) and quantum machine learning (QML) theoretically offer promising solutions to effectively address these challenges. In this work, we introduce a hybrid quantum–classical framework to predict binding affinity. Our approach involves, initially, the implementation of an efficient classical model using convolutional neural networks (CNNs) for feature extraction and three fully connected layers for prediction. Subsequently, retaining the classical module for feature extraction, we implement various quantum and classical modules for binding affinity prediction, which accept the concatenated features as input. Quantum predicted modules are implemented with Variational Quantum Regressions (VQRs), while classical predicted modules are implemented with various fully connected layers. Our findings clearly show that hybrid quantum–classical models accelerate the training process in terms of epochs and achieve faster stabilization. Also, these models demonstrate quantum superiority in terms of complexity, accuracy, and generalization, thereby indicating a promising direction for QML.
Noether Symmetries of the Triple Degenerate DNLS Equations
Authors: Camci Ugur
Published: July 2024

In this paper, Lie symmetries and Noether symmetries along with the corresponding conservation laws are derived for weakly nonlinear dispersive magnetohydrodynamic wave equations, also known as the triple degenerate derivative nonlinear Schrödinger equations. The main goal of this study is to obtain Noether symmetries of the second-order Lagrangian density for these equations using the Noether symmetry approach with a gauge term. For this Lagrangian density, we compute the conserved densities and fluxes corresponding to the Noether symmetries with a gauge term, which differ from the conserved densities obtained using Lie symmetries in Webb et al. (J. Plasma Phys. 1995, 54, 201–244; J. Phys. A Math. Gen. 1996, 29, 5209–5240). Furthermore, we find some new Lie symmetries of the dispersive triple degenerate derivative nonlinear Schrödinger equations for non-vanishing integration functions Ki(t) (i=1,2,3).
Exploring the Potential of Invasive Species Sargassum muticum: Microwave-Assisted Extraction Optimization and Bioactivity Profiling
Authors: Silva Aurora , Cassani Lucia , Carpena Maria , Lourenço-Lopes Catarina , Grosso Clara , Chamorro Franklin , García-Pérez Pascual , Carvalho Ana , Domingues Valentina F. , Barroso M. Fátima , Simal-Gandara Jesus , Prieto Miguel A.
Published: July 2024

Sargassum muticum (SM) poses a serious environmental issue since it is a fast-expanding invasive species occupying key areas of the European shoreline, disrupting the autochthonous algae species, and disturbing the ecosystem. This problem has concerned the general population and the scientific community. Nevertheless, as macroalgae are recognized as a source of bioactive molecules, the abundance of SM presents an opportunity as a raw material. In this work, response surface methodology (RSM) was applied as a tool for the optimization of the extraction of bioactive compounds from SM by microwave-assisted extraction (MAE). Five different parameters were used as target functions: yield, total phenolic content (TPC); and the antioxidant measurements of 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), and β-carotene bleaching (BC). After the optimal extraction conditions were determined (time = 14.00 min; pressure = 11.03 bar; ethanol = 33.31%), the chemical composition and bioactivity of the optimum extract was evaluated to appraise its antioxidant capability to scavenge reactive species and as a potential antibacterial, antidiabetic, antiproliferation, and neuroprotective agent. The results lead to the conclusion that MAE crude extract has bioactive properties, being especially active as an antiproliferation agent and as a nitric oxide and superoxide radical scavenger.