bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral Toxicity and Hypotensive Influence of Sericin-Derived Oligopeptides (SDOs) from Yellow Silk Cocoons of Bombyx mori in Rodent Studies
Authors: Tocharus Chainarong , Prum Virakboth , Sutheerawattananonda Manote
Published: November 2024

Sericin-derived oligopeptides (SDOs) from yellow silk cocoons exhibit antihypertensive and hypoglycemic properties in both in vitro and in vivo studies. This study investigated the acute toxicity of SDOs as a novel food for human consumption using female ICR mice and Wistar rats, as well as the chronic toxicity test on both sexes of Wistar rats. Clinical chemistry, hematology, and histopathological studies revealed that SDOs were safe for a single dose of 2000 mg kg−1 body weight (BW) and daily oral administration of 50, 100, and 200 mg kg−1 BW for six months. The chronic toxicity study additionally measured the rats’ systolic blood pressure (SBP) and blood sugar monthly as they slowly aged. In the 2nd month for male rats and the 4th month for both sexes, SDOs had a significant hypotensive effect on Wistar rats’ blood pressure, lowering it from 130 mmHg to a plateau at 110–115 mmHg. In contrast, the blood pressure of the control rats exceeded 140 mmHg after five months. Nonetheless, the hypoglycemic effect was not observed. Measurements of SBP and blood glucose in aged rats during chronic toxicity tests yielded insights beyond ordinary toxicity, including the health and fitness of the lab rats, perhaps resulting in novel discoveries or areas of study that justify the sacrifice of the animals’ lives.
Exploring the Potential of Anthocyanins for Repairing Photoaged Skin: A Comprehensive Review
Authors: Guo Xinmiao , He Linlin , Sun Jiaqiang , Ye Hua , Yin Cuiyuan , Zhang Weiping , Han Hao , Jin Wengang
Published: November 2024

Long-term exposure to ultraviolet (UV) rays can result in skin photoaging, which is primarily characterized by dryness, roughness, pigmentation, and a loss of elasticity. However, the clinical drugs commonly employed to treat photoaged skin often induce adverse effects on the skin. Anthocyanins (ACNs) are water-soluble pigments occurring abundantly in various flowers, fruits, vegetables, and grains and exhibiting a range of biological activities. Studies have demonstrated that ACNs contribute to the repair of photoaged skin due to their diverse biological characteristics and minimal side effects. Evidence suggests that the stability of ACNs can be enhanced through encapsulation or combination with other substances to improve their bioavailability and permeability, ultimately augmenting their efficacy in repairing photoaged skin. A growing body of research utilizing cell lines, animal models, and clinical studies has produced compelling data demonstrating that ACNs mitigate skin photoaging by reducing oxidative stress, alleviating the inflammatory response, improving collagen synthesis, alleviating DNA damage, and inhibiting pigmentation. This review introduces sources of ACNs while systematically summarizing their application forms as well as mechanisms for repairing photoaged skin. Additionally, it explores the potential role of ACNs in developing functional foods. These findings may provide valuable insight into using ACNs as promising candidates for developing functional products aimed at repairing photoaged skin.
Deterministic and Stochastic Analysis of Fractional-Order Legendre Filter with Uncertain Parameters
Authors: Hassan Mohammed A. , Amgad Andrew , Galal Osama H.
Published: November 2024

Fractional order filters are increasingly used due to their flexibility and continuous stepped stopband attenuation rate. The current work presents a deterministic design plan for an optimal fractional-order Legendre low-pass filter along with a stochastic investigation of its parametric uncertainty. First, the filter’s order was determined using the provided parameters, then the flower pollination algorithm was used to tune the transfer function parameters. This method uses the phase delay and magnitude response functions to quantify the desired output. Circuit diagrams, LT spice simulations, and a case study were used to validate the method. In addition, the effects of various components on stability and the performance metrics were further examined. Next, each of the described fractional system parameters (R1, R2, the ratio R4R3, Cα, and Cβ) was modeled as an uncertain term in a distinct cases, referred to as Cases I–V, respectively, and their combined effect was investigated as Case VI. These uncertain parameters were implemented using both random variables and stochastic processes. The system response was assessed using the Monte Carlo simulation method, and the mean, standard deviation, probability density function, and lower and upper bounds were plotted. Additionally, the key statistics of the cutoff frequency were tabulated in all cases. Many findings are addressed by the provided system solutions; briefly, the results revealed that the impact of uncertainty cases on system response, in descending order, was Case VI, Case III, Case V, Case II, Case I, and Case IV. Furthermore, the system demonstrated instability in Cases III and VI, which drew the designers’ attention to these two cases.
Green Synthesis of Silver Nanoparticles with Roasted Green Tea: Applications in Alginate–Gelatin Hydrogels for Bone Regeneration
Authors: Chavez-Granados Patricia Alejandra , Garcia-Contreras Rene , Reyes-Lopez Cesar A. S. , Correa-Basurto Jose , Hernandez-Rojas Irving E. , Hernandez-Gomez Gabriela , Jurado Carlos Alberto , Alhotan Abdulaziz
Published: November 2024

The incorporation of silver nanoparticles (AgNPs) into alginate–gelatin (Alg-Gel) hydrogels can enhance the properties of these materials for bone regeneration applications, due to the antimicrobial properties of AgNPs and non-cytotoxic concentrations, osteoinductive properties, and regulation of stem cell proliferation and differentiation. Here, the hydrogel formulation included 2% (w/v) sodium alginate, 4 µg/mL AgNPs, and 2.5% (w/v) gelatin. AgNPs were synthesized using a 2% (w/v) aqueous extract of roasted green tea with silver nitrate. The aqueous extract of roasted green tea for AgNP synthesis was characterized using HPLC and UHPLC-ESI-QTOF-MS/MS, and antioxidant capacity was measured in Trolox equivalents (TE) from 4 to 20 nmol/well concentrations. Stem cells from human exfoliated deciduous tooth cells were used for differentiation assays including positive (SHEDs/hydrogel with AgNPs) and negative controls (hydrogel without AgNPs). FTIR was used for hydrogel chemical characterization. Statistical analysis (p < 0.05, ANOVA) confirmed significant findings. Roasted green tea extract contained caffeine (most abundant), (−)-Gallocatechin, gallic acid, and various catechins. XRD analysis revealed FCC structure, TEM showed quasispheroidal AgNPs (19.85 ± 3 nm), and UV–Vis indicated a plasmon surface of 418 nm. This integration of nanotechnology and biomaterials shows promise for addressing bone tissue loss in clinical and surgical settings.
CIC-Related Neurodevelopmental Disorder: A Review of the Literature and an Expansion of Genotype and Phenotype
Authors: Ruiz Ivan , Wiltrout Kimberly , Stredny Coral , Mahida Sonal
Published: November 2024

Background: Genetic testing for neurodevelopmental disorders is now considered the standard of care for unexplained epilepsy as well as autism spectrum disorders, intellectual disability, and developmental delays with as many as 50% of individuals identified as having an underlying genetic etiology. Capicua (CIC) is a transcriptional repressor and is widely expressed among human brain tissue. Patients in the literature with pathogenic variants in CIC present with a broad spectrum of phenotypic abnormalities. Common features include epilepsy, developmental delay, intellectual disability, autism spectrum disorder, and MRI abnormalities amongst other neurodevelopmental symptoms. Variant type, age of onset, sex, and severity of manifestation also differ amongst probands. However, the full genotypic and phenotypic spectrum of CIC-related neurodevelopmental disorder has not been elucidated. Methods: Here we review patients reported in the literature with CIC variants and present two additional patients representing a novel genotype and phenotype. Results: Whole exome sequencing (WES) in this proband identified a novel paternally inherited likely pathogenic variant in CIC c.1526del p.(Pro509Hisfs*14). Both proband and father present with isolated epilepsy without other significant neurodevelopmental disorders. A review of the previous literature identified 20 individuals harboring CIC variants; the majority of these individuals present with a combination of neurodevelopmental features. Sixteen distinct variants were identified amongst these 20 patients. Conclusions: This family represents an expansion of the genotypic and phenotypic spectrum of CIC-related neurodevelopmental disorder. This information may lead to clinically actionable management changes for future patients identified with CIC variants considering standard anti-epileptic medication-weaning protocols.
Bridging the Gap Between Tolerogenic Dendritic Cells In Vitro and In Vivo: Analysis of Siglec Genes and Pathways Associated with Immune Modulation and Evasion
Authors: Jansen Diahann T. S. L. , Nikolic Tatjana , den Hollander Nicoline H. M. , Zwaginga Jaap Jan , Roep Bart O.
Published: November 2024

Background/Objectives: Dendritic cells (DCs) are master regulators of the adaptive immune response. Inflammatory DCs (inflamDCs) can prime inflammatory T cells in, for instance, cancer and infection. In contrast, tolerogenic DCs (tolDCs) can suppress the immune system through a plethora of regulatory mechanisms in the context of autoimmunity. We successfully generated tolDCs in vitro to durably restore immune tolerance to an islet autoantigen in type 1 diabetes patients in a clinical trial. However, cancers can induce inhibitory DCs in vivo that impair anti-tumor immunity through Siglec signaling. Methods: To connect in vivo and in vitro tolDC properties, we tested whether tolDCs generated in vitro may also employ the Siglec pathway to regulate autoimmunity by comparing the transcriptomes and protein expression of immature and mature inflamDCs and tolDCs, generated from monocytes. Results: Both immature DC types expressed most Siglec genes. The expression of these genes declined significantly in mature inflamDCs compared to mature tolDCs. Surface expression of Siglec proteins by DCs followed the same pattern. The majority of genes involved in the different Siglec pathways were differentially expressed by mature tolDCs, as opposed to inflamDCs, and in inhibitory pathways in particular. Conclusions: Our results show that tolDCs generated in vitro mimic tumor-resident inhibitory DCs in vivo regarding Siglec expression.
The Complexity of Familial Inheritance in Pectus Excavatum: A Ten-Family Exome Sequencing Analysis
Authors: Farina Juan M. , Olson Rory J. , Dhamija Radhika , Bofferding Anne , Sekulic Aleksandar , Egan Jan B. , Jaroszewski Dawn E.
Published: November 2024

Background/Objectives: Pectus excavatum (PEx) is considered, at least partially, a familial disorder. A variety of inheritance patterns, associations with genetic syndromes, and pathogenic variants have been reported. However, the etiology of this condition is still not completely understood, and no known genes have been identified as definitive contributors. Methods: Family members with a confirmed PEx diagnosis (one proband and two first-degree relatives) and non-affected members were recruited into this study. Exome sequencing was performed on all affected familial PEx cases to systematically screen for candidate genes that are likely to be causative for PEx, and on non-affected family members for variant segregation analysis. Results: Ten families, with three affected members each, participated, providing thirty familial PEx cases. Different inheritance patterns were represented across the ten pedigrees, with possible incomplete penetrance. Genetic variants in REST (essential for neuronal development and associated with pectus deformities in prior studies), SMAD4 (variants can predispose individuals to thoracic aortic diseases), and COL5A (associated with Ehlers–Danlos syndrome and Fibromuscular dysplasia) were initially identified as potentially linked to the development of pectus deformities and segregated with the phenotype. No variants were shared across families in the studied population. Conclusions: Germline exome sequencing of families with multiple individuals affected by PEx in our study identified potential gene candidates linked to PEx. These candidates are private to individual families and no strong candidates shared across multiple families were identified. These findings suggest that the inheritance of PEx may not be strongly related to a shared single genetic variant in known genes. Given the accumulating evidence for the genetic basis of familial PEx, further studies, including polygenic analyses, as well as assessment of the non-coding genome and possible epigenetic markers are warranted.
Inventory and Quantitative Assessment of Geosites in the Southern Sector of the Island of Malta
Authors: Possenelli Martina , Gauci Ritienne , Devoto Stefano , Selmi Lidia , Coratza Paola , Vandelli Vittoria
Published: November 2024

The island of Malta, despite its small size, boasts a great variety of landscapes and landforms, offering a wide range of geological and geomorphological features of great interest. The identification and assessment of geosites can contribute to the preservation, protection, and promotion of this rich geodiversity. In addition, geosites have a high potential of attracting geotourists, thus also contributing to the development of the local economy. Tourism plays a key role for the Maltese Islands, with Malta’s tourism direct contribution to GDP being among the highest in Europe. Thus, geotourism could represent a significant resource for Malta, though it has yet to receive the attention and recognition it deserves. Within this framework, this work aims to highlight the role of geoheritage and geotourism as potential resources for the enhancement of sustainable tourism and geoconservation in the southern sector of Malta. This region of Malta receives less visitors compared with the northern sector of the island, which is popular for its sandy beaches. To this end, potential geosites were inventoried and quantitatively assessed using a commonly applied methodology tailored to the local setting. The results of this evaluation let to identify 18 potential geosites that can be recognized as both parts of the Maltese natural heritage and tourist resources. Among these 18 sites, we identified four priority geosites which could be incorporated into a potential geotourism route to also highlight the valuable elements of the cultural heritage located in the vicinity. Moreover, the assessment methodology, applied for the first time in the investigated area, has proven to be a valuable support for geosite identification and can be extended to other Maltese regions.
Between Emptiness and Enslavement: The Role of Interpersonal Relationships in the Work of Ernst Weiß, Hermann Ungar, and Ludwig Winder
Authors: Smrkovsky Michal
Published: November 2024

This article explores the complex struggle for identity in the works of three prominent Moravia-born Prague German writers of the early twentieth century: Ernst Weiß, Hermann Ungar, and Ludwig Winder. It delves into the recurring motif of fear of intimacy and the paradoxical actions of their characters, who often view affection as a threat to their autonomy. Drawing on the psychoanalytic theories of Ronald Fairbairn and Harry Guntrip, the study examines how these authors depict this schizoid dilemma—the wish for interpersonal relationships, contrasting with the fear that love will lead to the destruction of the self. By analyzing selected works, the article identifies various coping mechanisms employed by the characters, such as emotional detachment, withdrawal into fantasies, and the creation of safe but ultimately hollow relationships. Through a comparative analysis, the paper reveals how these literary figures navigate their need for interpersonal connections while grappling with the terror of their own desires.
Assessing Differences in Groundwater Hydrology Dynamics Between In Situ Measurements and GRACE-Derived Estimates via Machine Learning: A Test Case of Consequences for Agroecological Relationships Within the Yazoo–Mississippi Delta (USA)
Authors: Heintzman Lucas J. , Ghaffari Zahra , Awawdeh Abdel R. , Barrett Damien E. , Yarbrough Lance D. , Easson Greg , Moore Matthew T. , Locke Martin A. , Yasarer Hakan I.
Published: November 2024

In situ groundwater monitoring is critical for irrigated agroecosystems and informs land cover changes. Yet, such data can pose management challenges and confound agroecological relationships. Correspondingly, satellite-based approaches, including the GRACE-constellation, are increasing. Although in situ and GRACE-derived comparisons occur, limited research considers agroecological dependencies. Herein, we examined differences in groundwater monitoring approaches (observed [in situ, O] vs. predicted [GRACE-derived, P]) within the Yazoo–Mississippi Delta (YMD), an agroecosystem in the southeastern USA. We compared variations in modeled groundwater hydrology, land cover, and irrigation dynamics of the YMD within the upper-quartile (UQ) area of interest (AOI) (highest groundwater levels) and lower-quartile (LQ) AOI (lowest groundwater levels) every year from 2008 to 2020. Spatially, OUQ and PUQ were in northern portions of the YMD, with the OLQ and PLQ in southern portions. Groundwater levels between OUQ:PUQ and OLQ:PLQ each had correlations > 0.85. Regarding land cover, most categories varied within ±2.50% between model estimates over time. Relatedly, we documented 14 instances where correlations between land use category and groundwater level were inverted across models (OLQ:PLQ (5), OUQ:OLQ (6), PUQ:PLQ (3)). Irrigation results were not statistically different among all models. Overall, our results highlight the importance of quantifying model incongruences for groundwater and land cover management.
Integrated Climate Change Mitigation and Public Health Protection Strategies: The Case of the City of Bologna, Italy
Authors: Nuvolari-Duodo Isabella , Dolcini Michele , Buffoli Maddalena , Rebecchi Andrea , Dall’Ò Giuliano , Monticelli Carol , Vertua Camilla , Brambilla Andrea , Capolongo Stefano
Published: November 2024

Introduction: The ongoing process of global warming, driven by the escalating concentration of greenhouse gases generated by human activities, especially in urban areas, significantly impacts public health. Local authorities play an important role in health promotion and disease prevention, and some aim to achieve net-zero greenhouse gas emissions. There is a consistent action underway to reach this goal, hence the need for mapping and implementing effective strategies and regulations. Materials and Methods: This study includes the analysis of policy guidelines adopted by the city of Bologna, consulted in March and April 2024. Bologna is one of the 100 cities committed to achieving climate neutrality by 2030, 20 years ahead of the EU target. To identify the strategies adopted to mitigate climate change, the following methodology was used: (i) the systematic mapping of sources and spatial planning documents; (ii) the extrapolation of goals, measures, and target indicators; and (iii) the development of an overall matrix. Results: The main findings of the study and their connection to public health pertain to the identification of key macro-areas contributing to the reduction of greenhouse gas emissions, while reducing the impact of climate change on health: (1) built environment and renewable energy sources, (2) transport and mobility, (3) energy, (4) green areas and land use, and (5) citizen support. Within these five macro-areas, 14 goals have been identified, to which a total of 36 measures correspond, and, finally, a target indicator is determined, mainly with respect to the reduction of tons of CO2 equivalent per year. Conclusions: In order to protect public health, it is evident that buildings and urban activities should not produce carbon emissions throughout their lifecycle. This paper presents a method to evaluate municipal policies regarding dual-impact solutions that address both environmental protection through sustainability strategies and public health, in compliance with the Health in All Policies (HiAP) approach.
“My Core Is Cracked”—Bullying in Higher Education as a Traumatic Process
Authors: Hodgins Margaret , Fahie Declan , MacCurtain Sarah , Kane Rhona , McNamara Patricia Mannix
Published: November 2024

Sectoral and institutional context[s] are critical to understanding how workplace toxicity manifests and how it might best be addressed. The education sector, specifically higher education, is the focus of this study, drawing on qualitative data collected from Irish Higher Education Institutions [HEIs]. Underpinned by a multi-faceted conceptualisation of bullying, the study explores how it is experienced by university staff and how institutional or contextual factors impinge on that experience. The study employed a qualitative interpretive methodology involving one-to-one semi-structured interviews with self-selecting participants. Persons who currently work or have recently worked in higher education institutions were recruited into the study. A generic thematic approach resulted in five intersecting themes, converging on one overarching organising construct, i.e., bullying in higher education as a traumatic process. The data displayed relationality, institutionalisation and unethicality, which are underlying features of a multi-faceted conceptualisation of bullying. It was concluded that the processes and procedures in place to address bullying and provide redress do not appear to be sufficiently nuanced to accommodate the complex behaviours and power plays involved in bullying in Higher Education, assuming a rationality stripped of power dynamics, which risks aggravating the damage already inflicted by bullying. The findings suggest that the institutional response, or lack thereof, can sometimes be more traumatising than the bullying itself. Individual cases often reflect a wider organisational culture that tolerates bullying and victimisation. Institutional responses will need to tackle the entire HEI ecosystem, requiring and a more nuanced understanding of the power dynamics and organisational context.
Corporate Social Responsibility and Country Governance: An International Comparative Study Amid the COVID-19 Pandemic
Authors: Vortelinos Dimitrios , Passas Ioannis , Floros Christos , Garefalakis Alexandros
Published: November 2024

This paper assesses the association of ESG scores with stock returns and highlights the moderating role of the COVID-19 pandemic and the country’s governance. The study uses panel data regression models to assess the relationship between ESG factors and stock returns, focusing on the moderating role of country governance and the COVID-19 pandemic. The results reveal that governance quality significantly enhances the positive effects of ESG practices on returns, particularly during times of crisis. These suggest that higher overall ESG scores are related positively to financial performance, and this relation is enhanced during the COVID-19 pandemic. Specifically, the two dimensions of ESG that matter most are environmental and governance. Country-level governance is important because firms in well-governed countries amplify the benefits of high ESG scores. The opposite is true for the higher controversies scores, whose bad financial outcome is magnified during the pandemic. These results present an argument for the resilience of firm financial performance, dependent on strong ESG practices and governance frameworks. This holds great interest for investors and policymakers in associating good ESG considerations with the effective management of financial risks, leading to sustainable returns during periods of widespread economic uncertainty.
Power Corridor Safety Hazard Detection Based on Airborne 3D Laser Scanning Technology
Authors: Wang Shuo , Zhao Zhigen , Liu Hang
Published: November 2024

Overhead transmission lines are widely deployed across both mountainous and plain areas and serve as a critical infrastructure for China’s electric power industry. The rapid advancement of three-dimensional (3D) laser scanning technology, with airborne LiDAR at its core, enables high-precision and rapid scanning of the detection area, offering significant value in identifying safety hazards along transmission lines in complex environments. In this paper, five transmission lines, spanning a total of 160 km in the mountainous area of Sanmenxia City, Henan Province, China, serve as the primary research objects and generate several insights. The location and elevation of each power tower pole are determined using an Unmanned Aerial Vehicle (UAV), which assesses the direction and elevation changes in the transmission lines. Moreover, point cloud data of the transmission line corridor are acquired and archived using a UAV equipped with LiDAR during variable-height flight. The data processing of the 3D laser point cloud of the power corridor involves denoising, line repair, thinning, and classification. By calculating the clearance, horizontal, and vertical distances between the power towers, transmission lines, and other surface features, in conjunction with safety distance requirements, information about potential hazards can be generated. The results of detecting these five transmission lines reveal 54 general hazards, 22 major hazards, and an emergency hazard in terms of hazards of the vegetation type. The type of hazard in the current working condition is mainly vegetation, and the types of cross-crossing hazards are power lines and buildings. The detection results are submitted to the local power department in a timely manner, and relevant measures are taken to eliminate hazards and ensure the normal supply of power resources. The research in this paper will provide a basis and an important reference for identifying the potential safety hazards of transmission lines in Henan Province and other complex environments and solving existing problems in the manual inspection of transmission lines.
Localization of Hemostasis Elements in Aspirated Coronary Thrombi at Different Stages of Evolution
Authors: Pituk Dóra , Balogh László , Horváth Emőke , Hegyi Zoltán , Baráth Barbara , Bogáti Réka , Szűcs Péter , Papp Zoltán , Katona Éva , Bereczky Zsuzsanna
Published: November 2024

The structure of aspirated coronary thrombus in ST-segment elevation myocardial infarction (STEMI) is still being studied. Our aims were to characterize coronary thrombi of different ages, focusing on the appearance of activated protein C (APC/PC) and its relation to the elements of neutrophil extracellular traps (NETs), and the factors closely related to fibrin as factor XIII (FXIII) and α2 plasmin inhibitor (α2-PI). The thrombi of n = 24 male patients with atherosclerotic coronary plaque rupture related to native coronary artery occlusion were selected for histopathology analysis. Thrombus age was distinguished as fresh, lytic, and organized, and then analyzed by immunofluorescent staining and confocal microscopy. FXIII was present at a high level and showed a high degree of co-localization with fibrin in all stages of thrombus evolution. The amount of α2-PI was low in the fresh thrombi, which increased significantly to the lytic phase. It was evenly distributed and consistently associated with fibrin. APC/PC appeared in the fresh thrombus and remained constant during its evolution. The presence of NET marker and CD66b was most dominant in the lytic phase. APC/PC co-localization with the elements of NET formation shows its role in NET degradation. These observations suggest the importance of searching for further targeted therapeutic strategies in STEMI patients.
Leucine-Enriched Diet Reduces Fecal MPO but Does Not Protect Against DSS Colitis in a Mouse Model of Crohn’s Disease-like Ileitis
Authors: Singh Drishtant , Menghini Paola , Rodriguez-Palacios Alexander , Martino Luca Di , Cominelli Fabio , Basson Abigail Raffner
Published: November 2024

Understanding the complex link between inflammation, gut health, and dietary amino acids is becoming increasingly important in the pathophysiology of inflammatory bowel disease (IBD). This study tested the hypothesis that a leucine-rich diet could attenuate inflammation and improve gut health in a mouse model of IBD. Specifically, we investigated the effects of a leucine-rich diet on dextran sulfate sodium (DSS)-induced colitis in germ-free (GF) SAMP1/YitFC (SAMP) mice colonized with human gut microbiota (hGF-SAMP). hGF-SAMP mice were fed one of four different diets: standard mouse diet (CHOW), American diet (AD), leucine-rich AD (AD + AA), or leucine-rich CHOW diet (CH + AA). Body weight, myeloperoxidase (MPO) activity, gut permeability, colonoscopy scores, and histological analysis were measured. Mice on a leucine-rich CHOW diet showed a decrease in fecal MPO prior to DSS treatment as compared to those on a regular diet (p > 0.05); however, after week five, prior to DSS, this effect had diminished. Following DSS treatment, there was no significant difference in gut permeability, fecal MPO activity, or body weight changes between the leucine-supplemented and control groups. These findings suggest that while a leucine-rich diet may transiently affect fecal MPO levels in hGF-SAMP mice, it does not confer protection against DSS-induced colitis symptoms or mitigate inflammation in the long term.
Salivary Metabolic Pathway Alterations in Brazilian E-Cigarette Users
Authors: Carvalho Bruna Fernandes do Carmo , Faria Natalia de Carvalho , Silva Kethilyn Chris Sousa , Greenfield Ellen , Alves Mônica Ghislaine Oliveira , Dias Meriellen , Mendes Maria Anita , Pérez-Sayáns Mario , Almeida Janete Dias
Published: November 2024

In recent years, the use of electronic cigarettes (e-cigs) has increased. However, their long-term effects on oral health and saliva remain poorly understood. Therefore, this study aimed to evaluate the saliva of e-cig users and investigate possible biomarkers. Participants were divided into two groups: the Electronic Cigarette Group (EG)—25 regular and exclusive e-cig users—and Control Group (CG)—25 non-smokers and non-e-cig users, matched in sex and age to the EG. The clinical analysis included the following parameters: age, sex, heart rate, oximetry, capillary blood glucose, carbon monoxide (CO) concentration in exhaled air, and alcohol use disorder identification test (AUDIT). Qualitative and quantitative analyses of saliva included sialometry, viscosity, pH, and cotinine concentrations. Furthermore, the EG and CG salivary metabolomes were compared using gas chromatography coupled with mass spectrometry (GC-MS). Data were analyzed using the Mann–Whitney test. The MetaboAnalyst 6.0 software was used for statistical analysis and biomarker evaluation. The EG showed high means for exhaled CO concentration and AUDIT but lower means for oximetry and salivary viscosity. Furthermore, 10 metabolites (isoleucine, 2-hydroxyglutaric acid, 3-phenyl-lactic acid, linoleic acid, 3-hydroxybutyric acid, 1,6-anhydroglucose, glucuronic acid, valine, stearic acid, and elaidic acid) were abundant in EG but absent in CG. It was concluded that e-cig users had high rates of alcohol consumption and experienced significant impacts on their general health, including increased cotinine and CO concentration in exhaled air, decreased oximetry, and low salivary viscosity. Furthermore, they showed a notable increase in salivary metabolites, especially those related to inflammation, xenobiotic metabolism, and biomass-burning pathways.
Angular-Substituted [1,4]Thiazino[3,4-a]Isoquinolines: Biological Evaluation and In Silico Studies on DPP-IV Inhibition
Authors: Pashev Aleksandar , Petrov Valentin , Pesheva Aleksandrina , Petrova Lidiya , Ilieva Kalina , Stavreva Galya , Atanasova Milena , Cheshmedzhieva Diana , Altankov George , Aleksandrova Teodora
Published: November 2024

Recent studies have discovered that aryl-substituted pyrido[2,1-a]isoquinolines have the potential to be highly active DPP IV inhibitors. In previous studies, we reported a novel synthetic approach for the construction of their sulfur-containing bioisosteric [1,4]thiazino[3,4-a]isoquinolines analogues, incorporating an additional aryl substituent. The present study aims to investigate the DPP IV inhibitory activity and cytotoxicity of the synthesized molecules by in vitro assay. The geometry optimization and molecular docking of the synthesized compounds were used to determine their binding modes to the active site of DPP IV. The docking analysis revealed that the energy-minimized poses of the studied compounds are close to the most important selectivity cliffs for DPP IV inhibition, forming hydrogen bonds and hydrophobic interactions with them. These results can be considered as a preliminary step towards further structural activity modifications.
GPCR-like Protein ZmCOLD1 Regulate Plant Height in an ABA Manner
Authors: Zhang Xinyuan , Zhang Zhen , Peng Hui , Wang Zimeng , Li Heng , Duan Yongqi , Chen Shuo , Chen Xidong , Dong Jinlei , Si Weina , Gu Longjiang
Published: November 2024

G protein-coupled receptors (GPCRs) are sensors for the G protein complex to sense changes in environmental factors and molecular switches for G protein complex signal transduction. In this study, the homologous gene of GPCR-like proteins was identified from maize and named as ZmCOLD1. Subcellular analysis showed that the ZmCOLD1 protein is localized to the cell membrane and endoplasmic reticulum. A CRISPR/Cas9 knock-out line of ZmCOLD1 was further created and its plant height was significantly lower than the wild-type maize at both the seedling and adult stages. Histological analysis showed that the increased cell number but significantly smaller cell size may result in dwarfing of zmcold1, indicating that the ZmCOLD1 gene could regulate plant height development by affecting the cell division process. Additionally, ZmCOLD1 was verified to interact with the maize Gα subunit, ZmCT2, though the central hydrophilic loop domain by in vivo and in vitro methods. Abscisic acid (ABA) sensitivity analysis by seed germination assays exhibited that zmcold1 were hypersensitive to ABA, indicating its important roles in ABA signaling. Finally, transcriptome analysis was performed to investigate the transcriptional change in zmcold1 mutant. Overall, ZmCOLD1 functions as a GPCR-like protein and an important regulator to plant height.
The Impact of Gestational Diabetes Mellitus on Minipuberty in Girls
Authors: Kowalcze Karolina , Burgio Sofia , Gullo Giuseppe , Kula-Gradzik Joanna , Ott Johannes , Krysiak Robert
Published: November 2024

Minipuberty is the second phase of physiological activation of the reproductive axis, playing a role in the postnatal development of sexual organs. The course of female minipuberty was found to be affected by low maternal vitamin D status and hypothyroidism during pregnancy. The aim of the current study was to assess the hormonal profile and the size of sexual organs in daughters of mothers with gestational diabetes mellitus. The study included three matched groups of infant girls: daughters of healthy women without metabolic disorders during pregnancy (group 1), daughters of women with poorly controlled gestational diabetes mellitus (group 2), and daughters of women with gestational diabetes mellitus adequately controlled during pregnancy (group 3). Urinary levels of gonadotropins, salivary levels of estradiol, testosterone, DHEA-S and progesterone, ovarian volume, uterine length and breast diameter were measured from postnatal month 1 to postnatal month 18. Concentrations of FSH, LH and estradiol were higher, while concentration of progesterone was lower in group 2 than in the remaining groups. There were no between-group differences in concentrations of testosterone and DHEA-S. Levels of LH, FSH, estradiol and progesterone correlated with maternal whole-blood levels of glycated hemoglobin. Group 2 was also characterized by the longest detection periods for LH and estradiol. Ovarian volume, uterine length and breast diameter were greater in group 1 than in the remaining two groups. Over the entire observation period, there were no differences in hormone levels and sizes of the sexual organs between groups 1 and 3. The obtained results suggest that poorly controlled, but not well controlled, gestational diabetes mellitus affects the course of female minipuberty.
Systematic Characteristics of Fucoidan: Intriguing Features for New Pharmacological Interventions
Authors: Jeong Seungjin , Lee Seokmin , Lee Geumbin , Hyun Jimin , Ryu Bomi
Published: November 2024

Fucoidan, a sulfated polysaccharide found primarily in brown algae, is known for exhibiting various biological activities, many of which have been attributed to its sulfate content. However, recent advancements in techniques for analyzing polysaccharide structures have highlighted that not only the sulfate groups but also the composition, molecular weight, and structures of the polysaccharides and their monomers play a crucial role in modulating biological effects. This review comprehensively provides the monosaccharide composition, degree of sulfation, molecular weight distribution, and linkage of glycosidic bonds of fucoidan, focusing on the diversity of its biological activities based on various characteristics. The implications of these findings for future applications and potential therapeutic uses of fucoidan are also discussed.
A Standardized Mouse Model for Wound Infection with Pseudomonas aeruginosa
Authors: Hou Jie , Wu Qian , Xiong Rongrong , Malakar Pradeep K. , Zhu Yongheng , Zhao Yong , Zhang Zhaohuan
Published: November 2024

Pseudomonas aeruginosa is a highly drug-resistant pathogen known to impair wound healing and provoke inflammatory responses, potentially leading to immune dysregulation. This study aimed to systematically investigate the immune response mechanisms mediated by cytokines following P. aeruginosa infection through the development of a standardized wound model. Kunming mice were selected as experimental subjects and given 8 mm diameter lesions on their backs and inoculated with standard strains PAO1 and PA14. The key parameters assessed included changes in body weight, wound redness and swelling, bacterial dynamics, protein content in wound tissues, immune responses, and pathological alterations. The results demonstrated that pathogen invasion significantly inhibited wound healing, with healing rates in the infected groups (87.5 ± 6.3% and 77.1 ± 3.6%) being notably lower than those in the uninfected control group. P. aeruginosa persisted in the wounds for up to 12 days, with bacterial loads decreasing from 8 log to 2 log. Additionally, there was a marked reduction in the protein content of the wound tissue and an increase in the expression levels of inflammatory factors such as IL-1β and TNF-α. The thickness of granulation tissue and the number of neovessels were significantly lower compared to the uninfected control group. This study establishes a standardized paradigm for creating a mouse model of P. aeruginosa infection in wounds, emphasizing the importance of appropriate mouse strains, uniform wound preparation methods, and moderate inoculation doses for reliable and accurate experimental results. These elements will facilitate the assessment of changes across six key indicators post-infection, providing a foundational data set and technical support for future mechanistic investigations of P. aeruginosa infection and the development of targeted antimicrobial strategies.
Structure, Function and Engineering of the Nonribosomal Peptide Synthetase Condensation Domain
Authors: Huang Zhenkuai , Peng Zijing , Zhang Mengli , Li Xinhai , Qiu Xiaoting
Published: November 2024

The nonribosomal peptide synthetase (NRPS) is a highly precise molecular assembly machinery for synthesizing structurally diverse peptides, which have broad medicinal applications. Withinthe NRPS, the condensation (C) domain is a core catalytic domain responsible for the formation of amide bonds between individual monomer residues during peptide elongation. This review summarizes various aspects of the C domain, including its structural characteristics, catalytic mechanisms, substrate specificity, substrate gating function, and auxiliary functions. Moreover, through case analyses of the NRPS engineering targeting the C domains, the vast potential of the C domain in the combinatorial biosynthesis of peptide natural product derivatives is demonstrated.
Exploring the Correlation Between the Molecular Structure and Biological Activities of Metal–Phenolic Compound Complexes: Research and Description of the Role of Metal Ions in Improving the Antioxidant Activities of Phenolic Compounds
Authors: Chen Zhe , Świsłocka Renata , Choińska Renata , Marszałek Krystian , Dąbrowska Aleksandra , Lewandowski Włodzimierz , Lewandowska Hanna
Published: November 2024

We discussed and summarized the latest data from the global literature on the action of polyphenolic antioxidants and their metal complexes. The review also includes a summary of the outcomes of theoretical computations and our many years of experimental experience. We employed various methods, including spectroscopy (FT-IR, FT-Raman, NMR, UV/Vis), X-ray diffraction, thermal analysis, quantum calculations, and biological assays (DPPH, ABTS, FRAP, cytotoxicity, and genotoxicity tests). According to our research, the number and position of hydroxyl groups in aromatic rings, as well as the delocalization of electron charge and conjugated double bonds, have a major impact on the antioxidant effectiveness of the studied compounds. Another important factor is metal complexation, whereby high ionic potential metals (e.g., Fe(III), Cr(III), Cu(II)) enhance antioxidant properties by stabilizing electron charge, while the low ionic potential metals (e.g., Ag(I), Hg(II), Pb(II)) reduce efficacy by disrupting electron distribution. However, we observed no simple correlation between ionic potential and antioxidant capacity. This paper gives insights that will aid in identifying new, effective antioxidants, which are vital for nutrition and the prevention of neurodegenerative illnesses. Our results outline the connections between biological activity and molecular structure, offering a foundation for the methodical design of antioxidants. Our review also shows in detail how we use various complementary methods to assess the impact of metals on the electronic systems of ligands. This approach moves beyond the traditional “trial and error” method, allowing for the more efficient and rational development of future antioxidants.
Artificial Intelligence (AI) Integration in Urban Decision-Making Processes: Convergence and Divergence with the Multi-Criteria Analysis (MCA)
Authors: Guarini Maria Rosaria , Sica Francesco , Segura Alejandro
Published: November 2024

The dynamics underpinning the urban landscape change are primarily driven by social, economic, and environmental issues. Owing to the population’s fluctuating needs, a new and dual perspective of urban space emerges. The Artificial Intelligence (AI) of a territory, or the system of technical diligence associated with the anthropocentric world, makes sense in the context of this temporal mismatch between territorial processes and utilitarian apparatus. This creates cerebral connections between several concurrent decision-making systems, leading to numerous perspectives of the same urban environment, often filtered by the people whose interests direct the information flow till the transformability. In contrast to the conventional methodologies of decision analysis, which are employed to facilitate convenient judgments between alternative options, innovative Artificial Intelligence tools are gaining traction as a means of more effectively evaluating and selecting fast-track solutions. The study’s goal is to investigate the cross-functional relationships between Artificial Intelligence (AI) and current decision-making support systems, which are increasingly being used to interpret urban growth and development from a multi-dimensional perspective, such as a multi-criteria one. Individuals in charge of administering and governing a territory will gain from artificial intelligence techniques because they will be able to test resilience and responsibility in decision-making circumstances while also responding fast and spontaneously to community requirements. The study evaluates current grading techniques and recommends areas for future upgrades via the lens of the potentials afforded by AI technology to the establishment of digitization pathways for technological advancements in the urban valuation.
The Personality of the Intelligent Cockpit? Exploring the Personality Traits of In-Vehicle LLMs with Psychometrics
Authors: Lin Qianli , Hu Zhipeng , Ma Jun
Published: November 2024

The development of large language models (LLMs) has promoted a transformation of human–computer interaction (HCI) models and has attracted the attention of scholars to the evaluation of personality traits of LLMs. As an important interface for the HCI and human–machine interface (HMI) in the future, the intelligent cockpit has become one of LLM’s most important application scenarios. When in-vehicle intelligent systems based on in-vehicle LLMs begin to become human assistants or even partners, it has become important to study the “personality” of in-vehicle LLMs. Referring to the relevant research on personality traits of LLMs, this study selected the psychological scales Big Five Inventory-2 (BFI-2), Myers–Briggs Type Indicator (MBTI), and Short Dark Triad (SD-3) to establish a personality traits evaluation framework for in-vehicle LLMs. Then, we used this framework to evaluate the personality of three in-vehicle LLMs. The results showed that psychological scales can be used to measure the personality traits of in-vehicle LLMs. In-vehicle LLMs showed commonalities in extroversion, agreeableness, conscientiousness, and action patterns, yet differences in openness, perception, decision-making, information acquisition methods, and psychopathy. According to the results, we established anthropomorphic personality personas of different in-vehicle LLMs. This study represents a novel attempt to evaluate the personalities of in-vehicle LLMs. The experimental results deepen our understanding of in-vehicle LLMs and contribute to the further exploration of personalized fine-tuning of in-vehicle LLMs and the improvement in the user experience of the automobile in the future.