bluuebunny/crossref_metadata_2025 huggingface dataset:
Branched-Chain Amino Acid (BCAA) Oligopeptide Determination from Whey Proteins: Preparation, Peptide Profiles, and Anti-Fatigue Activity
Authors: Zhu Qiong , Zhou Renjie , Zhu Xiping , Lu Xiangru , Ai Binli , Zhuang Qibin , Cui Chun
Published: December 2024

Whey proteins have anti-fatigue activity, but there are few studies that have reported the ameliorative effects of branched-chain amino acid (BCAA) oligopeptides from whey proteins on fatigue in mice. The purposes of this study were to establish a process for the preparation of BCAA oligopeptides from whey protein and to investigate the anti-fatigue activity of BCAA oligopeptides. Whey proteins were hydrolyzed by trypsin and flavourzyme and purified by ethanol precipitation and reversed-phase high performance liquid chromatography (RP-HPLC). Fraction D’ was found to contain the highest content of BCAAs and a high proportion of low-molecular-weight peptides (<1 kDa; content: 81.48%). Subsequently, mass spectrometry identified 15 BCAA oligopeptides in Fraction D’, including three dipeptides, six tripeptides, two tetrapeptides, and four pentapeptides. In addition, animal experiments showed that BCAA oligopeptides significantly prolonged the residence time on the rod and swimming time of mice. Further studies showed that BCAA oligopeptides remarkably reduced serotonin (5-hydroxytryptamine, 5-HT) synthesis in the brain by down-regulating the plasma-free tryptophan (F-Trp)/BCAA ratio, thereby alleviating fatigue. Therefore, BCAA oligopeptides can be used as an auxiliary functional dietary molecule in functional products to exert anti-fatigue activity by regulating 5-HT synthesis.
Antioxidant Bio-Compounds from Chestnut Waste: A Value-Adding and Food Sustainability Strategy
Authors: Barletta Roberta , Trezza Alfonso , Bernini Andrea , Millucci Lia , Geminiani Michela , Santucci Annalisa
Published: December 2024

In an era of escalating environmental challenges, converting organic residues into high-value bioactive compounds provides a sustainable way to reduce waste and enhance resource efficiency. This study explores the potential of the circular bioeconomy through the valorization of agricultural byproducts, with a focus on the antioxidant properties of specific chestnut burr cultivars. Currently, over one-third of food production is wasted, contributing to both humanitarian and environmental crises. Through circular bioeconomy, we can transform biological waste into valuable products for use in fields like food innovation and sustainability. The antioxidant effects of three chestnut cultivars, Bastarda Rossa, Cecio, and Marroni, were assessed through in vitro assays, highlighting their potential to combat oxidative stress—an important factor for health-related applications. The characterization of the three cultivars showed the major presence of ellagic acid and gallic acid in the extract, renowned for their antioxidant activity. In vitro assays evaluated the phenolic and flavonoid content, as well as the antioxidant activity of the three extracts, confirming the cultivar Cecio as the richest in these bioactive compounds and the most performative in antioxidant assays. In vitro antioxidant and oxidative stress recovery assays on SaOS-2, fibroblast, and chondrocyte cell lines displayed a strong antioxidant activity. Furthermore, the cytotoxicity assay demonstrated the safety of all three extracts in the tested human cell lines. In silico docking simulations further validated the biological relevance of these compounds by predicting strong hydrophobic and polar interactions with oxidative stress-related protein targets. Overall, this study demonstrates the antioxidant properties of chestnut byproducts. The findings contribute to the development of functional foods, nutraceuticals, and other applications, underscoring the role of chestnut cultivars in advancing circular bioeconomy practices.
AbaComplex Enhances Mitochondrial Biogenesis and Adipose Tissue Browning: Implications for Obesity and Glucose Regulation
Authors: Sagliocchi Serena , Schiano Elisabetta , Acampora Lucia , Iannuzzo Fortuna , Cicatiello Annunziata Gaetana , Miro Caterina , Nappi Annarita , Restolfer Federica , Stornaiuolo Mariano , Zarrilli Stefano , Guerra Fabrizia , Tenore Gian Carlo , Dentice Monica , Novellino Ettore
Published: December 2024

Adipose tissue, particularly white adipose tissue (WAT), plays a central role in energy storage and metabolic regulation. Excess WAT, especially visceral fat, is strongly linked to metabolic disorders such as obesity and type 2 diabetes. The browning of WAT, whereby white fat cells acquire characteristics of brown adipose tissue (BAT) with enhanced thermogenic capacity, represents a promising strategy to enhance metabolic health. In this study, we investigated the effects of chronic supplementation with an infusion based on lyophilized, thin nectarines rich in abscisic acid (ABA), named AbaComplex, on promoting browning of WAT and activating BAT in mice. Over 30 days, C57BL/6 mice were treated with the ABA-rich infusion, and various metabolic and molecular parameters were assessed. The results showed that the AbaComplex significantly increased the expression of browning markers, such as UCP1 and PGC1-α, in both visceral and subcutaneous WAT. Additionally, mitochondrial biogenesis and function were enhanced, evidenced by elevated mitochondrial DNA content and activity. The treatment also reduced the weight of WAT (both visceral and subcutaneous) and BAT and significantly improved glucose uptake in WAT via upregulation of GLUT4, suggesting enhanced insulin sensitivity. Overall, the pronounced browning effect in WAT underscores the potential of AbaComplex as a natural approach for combating obesity and improving metabolic health.
Sandwich-Type Results and Existence Results of Analytic Functions Associated with the Fractional q-Calculus Operator
Authors: Palei Sudhansu , Soren Madan Mohan , Breaz Daniel , Cotîrlǎ Luminiţa-Ioana
Published: December 2024

In the present investigation, we present certain subordination and superordination results for the q-integral operator of a fractional order associated with analytic functions in the open unit disk U. Using this q-integral operator, we obtain sandwich-type results. Furthermore, we employ the existence of univalent solutions to a q-differential equation connected with a fractional q-integral operator of fractional order. We use these results to demonstrate the significance of our findings for particular functions. We also derive some examples and corollaries that are pertinent to our results.
Thermosensitive In Situ Ophthalmic Gel for Effective Local Delivery and Antifungal Activity of Ketoconazole Nanoparticles
Authors: Chaiwut Chutima , Tadtong Sarin , Akachaipaibul Puriputt , Jiaranaikulwanitch Jutamas , Singh Sudarshan , Okonogi Siriporn , Syukri Dwi Marlina , Chittasupho Chuda
Published: December 2024

Fungal keratitis is a severe ocular infection caused by pathogenic fungi, leading to potential vision loss if untreated. Current antifungal treatments face limitations such as low solubility, poor corneal penetration, and limited therapeutic options. This study aimed to develop a thermosensitive in situ gel incorporating ketoconazole nanoparticles (NPs) to enhance drug solubility, stability, and antifungal activity. Ketoconazole NPs were prepared using the solvent displacement method, achieving a particle size of 198.25 ± 27.51 nm, encapsulation efficiency of 94.08 ± 0.51%, polydispersity index of 0.42 ± 0.08, and a positive zeta potential value of +10.08 ± 0.19 mV. The NPs exhibited sustained zero-order release kinetics. The optimized NPs were incorporated into a poloxamer-based in situ gel, demonstrating a gelation temperature of 34.67 ± 0.58 °C and the shortest gelation time. The formulation provided a 5-fold increase in solubility and a 10-fold improvement in drug release compared to pure ketoconazole. Stability studies confirmed the gel retained its physicochemical and rheological properties for three months under various storage conditions. The in situ gel showed sustained release, effective antifungal activity against Malassezia furfur, and good tolerability, suggesting it as a promising alternative for treating fungal keratitis with improved bioavailability and patient compliance.
Model Organisms in Aging Research: Evolution of Database Annotation and Ortholog Discovery
Authors: Sarygina Elizaveta , Kliuchnikova Anna , Tarbeeva Svetlana , Ilgisonis Ekaterina , Ponomarenko Elena
Published: December 2024

Background: This study aims to analyze the exploration degree of popular model organisms by utilizing annotations from the UniProtKB (Swiss-Prot) knowledge base. The research focuses on understanding the genomic and post-genomic data of various organisms, particularly in relation to aging as an integral model for studying the molecular mechanisms underlying pathological processes and physiological states. Methods: Having characterized the organisms by selected parameters (numbers of gene splice variants, post-translational modifications, etc.) using previously developed information models, we calculated proteome sizes: the number of possible proteoforms for each species. Our analysis also involved searching for orthologs of human aging genes within these model species. Results: Our findings indicate that genomic and post-genomic data for more primitive species, such as bacteria and fungi, are more comprehensively characterized compared to other organisms. This is attributed to their experimental accessibility and simplicity. Additionally, we discovered that the genomes of the most studied model organisms allow for a detailed analysis of the aging process, revealing a greater number of orthologous genes related to aging. Conclusions: The results highlight the importance of annotating the genomes of less-studied species to identify orthologs of marker genes associated with complex physiological processes, including aging. Species that potentially possess unique traits associated with longevity and resilience to age-related changes require comprehensive genomic studies.
Determination of Stable Reference Genes for Gene Expression Analysis in Black Rockfish (Sebastes schlegeli) Under Hypoxia Stress
Authors: Chen Xiatian , Yu Yujie , Gao Tao , Liu Zhifei , Chen Shuaiyu , Jia Yudong
Published: December 2024

Background: Hypoxia triggers stress, leading to significant alterations in gene expression patterns, which in turn affect fish’s growth and development. Real-time quantitative PCR (RT-qPCR) is a pivotal technique for assessing changes in gene expression. However, its accuracy is highly contingent upon the stable expression of reference genes. Ribosomal RNA (18s), β-actin (actb), elongation factor 1-α (ef1a), α tubulin (tuba), and ribosomal protein L17 (rpl17) are the widely used reference genes, but their expression stability in the tissues of black rockfish under hypoxic conditions remains unclear. Methods: The expression of genes was detected by RT-qPCR and the stability was assessed by Delta Ct, geNorm, NormFinder, and BestKeeper algorithms. Results: Results showed that tuba exhibited stable expression in liver, heart, gill tissues under normoxic conditions, and in the liver and head kidney under hypoxic conditions. Ef1a was identified as the most stably expressed gene in gill tissue under hypoxia. For hypoxic heart studies, rpl17 and tuba were recommended as reference genes. 18s showed high stability in spleen tissue under hypoxic conditions. Actb was the most stably expressed gene in spleen and head kidney tissues under normoxic conditions. Conclusions: The identified reference genes exhibited tissue-specific stability, and it was necessary to select appropriate reference genes based on the specific tissue type for gene expression studies under hypoxic conditions. These findings help in enhancing the accuracy of gene expression analysis in the mechanism of hypoxia for black rockfish.
Transcriptomic Evidence Reveals the Dysfunctional Mechanism of Synaptic Plasticity Control in ASD
Authors: Kong Chao , Bing Zhitong , Yang Lei , Huang Zigang , Wang Wenxu , Grebogi Celso
Published: December 2024

Background/Objectives: A prominent endophenotype in Autism Spectrum Disorder (ASD) is the synaptic plasticity dysfunction, yet the molecular mechanism remains elusive. As a prototype, we investigate the postsynaptic signal transduction network in glutamatergic neurons and integrate single-cell nucleus transcriptomics data from the Prefrontal Cortex (PFC) to unveil the malfunction of translation control. Methods: We devise an innovative and highly dependable pipeline to transform our acquired signal transduction network into an mRNA Signaling-Regulatory Network (mSiReN) and analyze it at the RNA level. We employ Cell-Specific Network Inference via Integer Value Programming and Causal Reasoning (CS-NIVaCaR) to identify core modules and Cell-Specific Probabilistic Contextualization for mRNA Regulatory Networks (CS-ProComReN) to quantitatively reveal activated sub-pathways involving MAPK1, MKNK1, RPS6KA5, and MTOR across different cell types in ASD. Results: The results indicate that specific pivotal molecules, such as EIF4EBP1 and EIF4E, lacking Differential Expression (DE) characteristics and responsible for protein translation with long-term potentiation (LTP) or long-term depression (LTD), are dysregulated. We further uncover distinct activation patterns causally linked to the EIF4EBP1-EIF4E module in excitatory and inhibitory neurons. Conclusions: Importantly, our work introduces a methodology for leveraging extensive transcriptomics data to parse the signal transduction network, transforming it into mSiReN, and mapping it back to the protein level. These algorithms can serve as potent tools in systems biology to analyze other omics and regulatory networks. Furthermore, the biomarkers within the activated sub-pathways, revealed by identifying convergent dysregulation, illuminate potential diagnostic and prognostic factors in ASD.
EDA Mutations Causing X-Linked Recessive Oligodontia with Variable Expression
Authors: Lee Ye Ji , Kim Youn Jung , Chae Wonseon , Kim Seon Hee , Kim Jung-Wook
Published: December 2024

Background/Objectives: The ectodysplasin A (EDA) gene, a member of the tumor necrosis factor ligand superfamily, is involved in the early epithelial–mesenchymal interaction that regulates ectoderm-derived appendage formation. Numerous studies have shown that mutations in the EDA gene can cause X-linked ectodermal dysplasia (ED) and non-syndromic oligodontia (NSO). Accordingly, this study aimed to identify the causative genetic mutations of the EDA gene. Methods: We investigated EDA gene mutations in two X-linked oligodontia families using candidate gene sequencing and whole-exome sequencing, with a single proband identified and studied for each family. The first family included a patient with NSO, while the second family had a patient exhibiting variable expression of ED. Results: Mutational analysis identified two missense mutations in the EDA gene (NM_001399.5): one novel mutation, c.787A>C p.(Lys263Gln), in family 2; and one previously reported mutation, c.457C>T p.(Arg153Cys), in family 1. All mutated residues are evolutionarily highly conserved amino acids. The p.(Arg153Cys) mutation would destroy the furin recognition site and affect the cleavage of EDA. The p.(Lys263Gln) mutation in a TNF homology domain would interfere with the binding of the EDA receptor. The p.(Lys263Gln) mutation was associated with NSO, while the other mutation demonstrated ED. Conclusions: This study helps to better understand the nature of EDA-related ED and NSO and their pathogenesis, and it expands the mutational spectrum of EDA mutations.
Opening Pandora’s Box: Exploring Body Image Perceptions and Influencing Factors in Women—An Interpretative Phenomenological Analysis
Authors: Adamidou Konstantina , Tragantzopoulou Panagiota
Published: December 2024

Background/Objectives: Body dissatisfaction among women has been on the rise, prompting an urgent need to understand the underlying factors influencing their body image. This study explores the perceptions and influencing factors of body image among women in Greek society. Methods: Six in-depth interviews were conducted and analyzed using Interpretative Phenomenological Analysis. Results: The findings reveal that negative comments from parents and romantic partners, pregnancy, and peer influences are key factors affecting women’s perceptions about their body. Body dissatisfaction was primarily driven by social media and a desire to feel attractive to the opposite gender, leading to extreme behaviors such as excessive exercise, low-calorie intake, and surgical procedures. The aspiration to undergo cosmetic surgeries was significantly influenced by social media portrayals of beauty. On the one hand, the ideal physique for women was characterized by curves and toned muscles, but on the other hand, women described the ideal self as being reconciled with their bodies and less self-critical. Conclusions: This study highlights the complex interplay of personal relationships and societal pressures in shaping women’s body image and underscores the need for more qualitative research in this area. Understanding these dynamics is crucial for developing interventions to mitigate the negative physical and mental health repercussions associated with body dissatisfaction.
Correlation Study Between TV Viewing Variables and Cognitive Level, Depression Level, and Activities of Daily Living in Older Individuals Living Alone
Authors: Oh Sung Yeon , Kwon Bum Sun , Nam Yeon Gyo
Published: December 2024

Background/objectives: Although there are studies on TV viewing and the health status of elderly, they do not present direct associations with specific variables. The aim of this study was to determine correlations between TV viewing variables and elderly health variables in older adults living alone. Methods: Data were collected from 50 elderly individuals with an average age of 82.12 ± 4.32 (Male 20%, Female 80%). Television viewing variables were collected via a TV set-top box, including the daily average viewing time, upper zapping threshold, lower zapping threshold, and average zapping per hour. The cognitive level was assessed using the Mini-Mental-State Examination, the depression level was assessed with the Geriatric Depression Scale, and activities of daily living were assessed using the Modified Barthel Index. Spearman correlation analysis was applied to the collected variables. Results: The results showed significant correlations between the depression level and both the daily average viewing time (r = 0.320) and upper zapping threshold (r = 0.308). The activities of daily living demonstrated significant correlations with the daily average viewing time (r = −0.313) and upper zapping threshold (r = −0.352). Conclusions: The TV viewing time and zapping are associated with depression and daily living activities, suggesting their potential as early diagnostic indicators for geriatric diseases in older adults living alone.
Unity in Diversity and Diversity in Unity—Vaccination Policies in EU Countries
Authors: Petrova-Geretto Elisaveta , Vodenitcharova Alexandrina , Petrova Guenka
Published: December 2024

Background/Objectives: This article emphasizes the comprehensive importance of vaccination, exploring its role in disease prevention, addressing growing concerns around vaccine hesitancy, and underscoring the crucial need for high vaccination coverage rates. Methods: Our review examines EU-level and national policies on vaccination, utilizing EU sources, with a specific focus on regulatory and policy documents. Vaccination calendars in the EU were reviewed through the ECDC Vaccine Scheduler webpage. The parameters of this literature review were further selected in collaboration with an Emory Health sciences librarian using the following search terms: healthcare providers, communication, public health, informed consent, and bioethics. Results: The analysis of limited articles on community engagement, moral and political philosophy, and public health ethics informs the ethical consideration of informed consent in public health interventions. Countries exhibit varying relationships between their vaccination programs and society, with technocratic and populist influences shaping vaccination policies. Conclusions: Europe demonstrates diversity in vaccination policies, with availability, funding, and scheduling reflecting distinct approaches to vaccination.
Optimizing Exclusion Criteria for Clinical Trials of Persistent Lyme Disease Using Real-World Data
Authors: Johnson Lorraine , Shapiro Mira , Needell Deanna , Stricker Raphael B.
Published: December 2024

Background/Objectives: Although eligibility criteria for clinical trials significantly impact study outcomes, these criteria are often established without scientific justification, leading to delayed recruitment, small sample sizes, and limited study generalizability. Persistent Lyme disease (PLD) presents unique challenges due to symptom variability, inconsistent treatment responses, and the lack of reliable biomarkers, underscoring the need for scientifically justified eligibility criteria. Objective: This study examines the effects of commonly used enrollment criteria on sample yield in PLD clinical trials using real-world data (RWD) from the MyLymeData patient registry. The study also compares the effects of these criteria on enrollment for PLD versus acute Lyme disease (ALD) trials and evaluates the scientific rationale for each criterion. Methods: Data from 4183 Lyme disease patients enrolled in the MyLymeData registry were analyzed to assess the prevalence and cumulative impact of various criteria on sample yield. A comparative analysis of cohorts with PLD (n = 3589) versus ALD (n = 594) was conducted to identify differences in sample attrition. Results: In a large PLD cohort study, we found that current commonly used eligibility criteria would exclude approximately 90% of patients, significantly limiting study generalizability. Substantial differences in sample attrition between PLD and ALD cohorts highlight the need for tailored criteria. The strength of scientific justification varied widely among criteria. Conclusions: This study demonstrates the importance of using RWD to optimize eligibility criteria in PLD clinical trials. By providing insights into the balance between sample attrition and scientific justification, researchers can enhance trial feasibility, generalizability, and robustness. Our RWD sample demonstrates that researchers could substantially increase the sample yield from 10% to 64% by loosening restrictions on coinfections and misdiagnoses of chronic fatigue syndrome, fibromyalgia syndrome, and psychiatric conditions.
A Study on Adolescent Smoking Prevention and Cessation Policies: Based on the Propensity Score Matching–Difference-in-Differences Method
Authors: Ji Seokmin , Moon Byungchan , Kwon Younggyu , Kim Kyumin
Published: December 2024

Introduction: Adolescent smoking can lead to various health problems including atherosclerosis and cardiovascular disease, making it more difficult to quit smoking during adulthood. This study aims to evaluate the effect of the ordinance by assessing adolescents’ smoking cessation behaviors and environmental conditions, according to the “Ordinance for the Prevention of Child and Adolescent Smoking and Support for Smoking Cessation”, which was enacted in 2019 in Gwangju City, South Korea, for the first time in the country. Methods: The data for the analysis were obtained from the 2018 and 2021 Korea Youth Risk Behavior Survey. Propensity score matching (PSM) ensured homogeneity between ordinance-adopted and non-adopted areas, followed by a difference-in-differences (DID) analysis to assess changes in adolescent smoking behavior, secondhand smoke exposure, and related advertisements. Results: The difference-in-differences analysis of the homogeneous treatment and control groups in 2018 and 2021 showed statistically significant reductions in the variables “experience of secondhand smoke indoors at school” in the secondhand smoke category, and “exposure to smoking advertisements in convenience stores” in the smoking advertising category. However, there were no statistically significant changes in the other eight variables, such as smoking behavior and smoking cessation advertising. Conclusions: The results of this study suggest that the ordinance enacted in Gwangju Metropolitan City in 2019 created a positive environment for smoking prevention in convenience stores and schools for adolescents. Furthermore, if the ordinance is supplemented with the management of smoking behaviors and smoking cessation advertisements, it is expected to achieve the main purpose of the policy, which is to protect adolescents from smoking.
Translation and Cultural Adaptation of an E-Health Program to Promote Positive Mental Health Among Family Caregivers in Portugal
Authors: Carreira Sandra , Albacar-Riobóo Núria , Ferré-Grau Carme , Sequeira Carlos , Andrade Carmen , Araújo Odete
Published: December 2024

Introduction: Caring for a dependent individual, particularly over an extended period, places significant strain on family caregivers, often leading to adverse physical, mental, emotional, social, and economic outcomes for both caregivers and those they care for. Common challenges include anxiety, depression, loneliness, and diminished overall well-being. E-health applications have emerged as effective tools to support family caregivers by promoting positive mental health through online interventions, enhancing problem-solving skills, autonomy, interpersonal relationships, self-control, and a prosocial attitude. Methods: This study aimed to translate and culturally adapt the Spanish “Program to Promote Positive Mental Health through the Cuidadoras Crónicos Manual” into the Portuguese context, supporting its implementation as a smartphone application. The process involved translation, back-translation by two native experts, and refinement through a focus group with eight participants. The study adhered to the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. Results: The translation and back-translation processes identified several adjustments, which informed discussions in the focus group. Three key themes emerged: (i) conceptual and semantic equivalence, (ii) optimisation of content, and (iii) relevance and timeliness of the manual. Conclusions: The Spanish manual for promoting positive mental health among family caregivers was successfully translated and culturally adapted into European Portuguese. Validated through expert input, this marks the first version of the manual tailored to Portuguese caregivers, using Positive Mental Health models to support caregivers of individuals with chronic conditions.
Badges of (Dis-)Honour: Manifesting the ‘Conquest’ of Uluṟu via Wearable Material Culture
Authors: Spennemann Dirk H. R. , Hurford Sharnie
Published: December 2024

Set in a wide open plain, the monolith of Uluṟu (‘Ayers Rock’) has become an internationally recognizable symbol for the Australian outback, currently attracting hundreds of thousands of tourists each year. Promoted since the 1950s as an exotic tourist destination, one of the major activities has been the ‘conquest’ of Uluṟu by completing the steep climb to the top. Always disapproved by the Aṉangu, the Indigenous Australian community of the area, and actively discouraged since 1990, the climb became an extremely contentious issue in the final two years before it was permanently closed to tourists on 26 October 2019. Given that climbing Uluṟu as a tourist activity has become an event of the past, this paper will examine the nature, materiality, and potential heritage value of the portable material culture associated with the climb. The background to the history of climbing Uluṟu in the context of European invasion (‘exploration’), the nature of tourism at Uluṟu and the role climbing played in this, as well as the management decisions that led to the closure of the climb can be grouped into four thematic periods: the beginnings of settler colonialist ascents (1873–1950), the ‘heroic’ age of Uluṟu tourism (1950–1958), lodges in a National Park (1958–1985), and joint management and the eventual closure of the climb (1985–2019). Based on a description of the material culture associated with the climb, particularly badges, patches and certificates, and drawing on the methodologies of historic and material culture studies, this paper will discuss the various interpretations of climbing Uluṟu and how the portable material culture reflects or exemplifies climbing as a conquest and heroic deed, as a spiritual ritual, and as a violation of cultural rights. After examining the materiality of the wearable material culture, we conclude by exploring which of these portable items are culturally significant and which, if any, should be curated in public collections.
Optimizing Cucumber (Cucumis sativus L.) Fruit Metabolomics Under Elevated CO2 and High-Temperature Stress in the Greenhouse
Authors: Du Xian , Song Yang , Pan Lu , Cui Shimao
Published: December 2024

Elevated carbon dioxide concentrations can mitigate the significant threats of high-temperature stress to the yield and quality of cucumber fruit during summer. This study aims to elucidate the response mechanisms of cucumber fruit metabolomics under elevated CO2 and high-temperature stress while also exploring the potential benefits of elevated CO2 in mitigating the adverse effects of high temperatures. The fruits of the experimental material cucumber (Cucumis sativus L., ’Jinyou 35’) were grown under soil conditions in the greenhouse. We used untargeted metabolomics methods to analyze the effects of varying temperatures (normal temperatures of 25 to 35 °C and high temperatures of 35 to 45 °C) and CO2 concentrations (400 ± 20 µmol/mol and 1200 ± 20 µmol/mol) on the morpho-physiological traits, yield-associated traits, and metabolomic profiles of cucumber fruits. The results showed that, under high-temperature stress, elevated carbon dioxide concentrations altered 27 differential metabolites, including tyramine, xylitol, linolenic acid, L-asparagine, α-linolenic acid, and L-phenylalanine. These alterations are associated with the metabolic pathways of alanine, aspartate, glutamate, glutathione, glyoxylate, and dicarboxylic acids. Compared to adding carbon dioxide at normal temperatures, elevated carbon dioxide at high temperatures modified 38 differential metabolites, including vitamin B6, L-citrulline, inositol, L-aspartic acid, sucrose, and palmitic acid. These modifications were linked to the galactose metabolic pathway and the zeatin and arginine biosynthetic pathways. The accumulation of cysteine, glutamic acid, and glycine is essential to form the antioxidant glutathione; thus, cucumber fruits with a higher amino acid content exhibit an enhanced capacity to withstand severe high-temperature stress. Under high-temperature conditions, elevated carbon dioxide adds complexity to changes in differential metabolites within cucumber fruits. These fruits accumulate sugars, organic acids, and amino acids through the galactose metabolism pathway (map00052), the arginine biosynthesis pathway (map00220), and the glutamate synthesis pathway (map00250), thereby improving their heat resistance.
The Experience of Social Exclusion and the Path to Inclusion from the Perspectives of Immigrant and Refugee Women in the Niagara Region
Authors: Crawford Joanne , Lundy Tara , Crawford Chiarina , Moore Jane , Viscek Nicole , Kapisavanhu Nyarayi
Published: December 2024

Social inclusion is a common goal for equitable access to resources for living, is important to health and wellbeing, and is supported by most Western or developed nations. Despite this, immigrant and refugee women continue to be excluded from social, cultural, economic, civic, and political participation during and after settlement. Most research exploring the context of social exclusion has reinforced that some groups experience greater exclusion than others in any given population, for example, immigrant women. The purpose of this study was to gain insights by exploring the experiences of social inclusion and exclusion and recommendations from the perspectives of immigrant and refugee women, as well as community service workers in the Niagara Region, Canada. Utilizing qualitative descriptive inquiry underpinned by intersectionality theory along with thematic analysis, we interviewed 10 immigrant and refugee women and 14 community service workers. Five themes were generated: (1) gendered nature of exclusion; (2) levels of exclusion; (3) paving a path for self; (4) formal inclusionary processes; and (5) informal inclusionary processes. The findings will be used to guide community action and may be transferable to community organizations that serve immigrant and refugee women in similar community contexts, with the aim of enhancing collaborations to advance health equity and inclusion.
Optimizing Site Selection for Construction: Integrating GIS Modeling, Geophysical, Geotechnical, and Geomorphological Data Using the Analytic Hierarchy Process
Authors: Wahba Doaa , Omran Awad A. , Adly Ashraf , Gad Ahmed , Arman Hasan , El-Bagoury Heba
Published: December 2024

Identifying suitable sites for urban, industrial, and tourist development is important, especially in areas with increasing population and limited land availability. Kharga Oasis, Egypt, stands out as a promising area for such development, which can help reduce overcrowding in the Nile Valley and Delta. However, soil and various environmental factors can affect the suitability of civil engineering projects. This study used Geographic Information Systems (GISs) and a multi-criteria decision-making approach to assess the suitability of Kharga Oasis for construction activities. Geotechnical parameters were obtained from seismic velocity data, including Poisson’s ratio, stress ratio, concentration index, material index, N-value, and foundation-bearing capacity. A comprehensive analysis of in situ and laboratory-based geological and geotechnical data from 24 boreholes examined soil plasticity, water content, unconfined compressive strength, and consolidation parameters. By integrating geotechnical, geomorphological, geological, environmental, and field data, a detailed site suitability map was created using the analytic hierarchy process to develop a weighted GIS model that accounts for the numerous elements influencing civil project design and construction. The results highlight suitable sites within the study area, with high and very high suitability classes covering 56.87% of the land, moderate areas representing 27.61%, and unsuitable areas covering 15.53%. It should be noted that many settlements exist in highly vulnerable areas, emphasizing the importance of this study. This model identifies areas vulnerable to geotechnical and geoenvironmental hazards, allowing for early decision-making at the beginning of the planning process and reducing the waste of effort. The applied model does not only highlight suitable sites in the Kharga Oasis, Egypt, but, additionally, it provides a reproducible method for efficiently assessing land use suitability in other regions with similar geological and environmental conditions around the world.
Marijuana Dispensary Locations and Neighborhood Characteristics in New York City
Authors: Yin Li , Wang Suiyuan , Patterson Kelly L. , Silverman Robert Mark , Rehman-Veal Ambreen
Published: December 2024

New York State (NYS) passed the Marijuana Regulation and Taxation Act (MRTA) in March of 2021 to legalize adult-use recreational cannabis that allows for its distribution, retail sale, and on-site consumption in licensed businesses. While the state (NYS) has imposed some spatial constraints on the dispensaries’ locations, it is unclear what the current spatial patterns of those dispensaries are and how they impact neighborhoods. This research explores how recreational cannabis relates spatially to neighborhood characteristics using New York City as a case study. We identified how cannabis stores are spatially correlated with neighborhood attributes, including socio-demographic and land use characteristics. Our results from the compliance check showed that the highest noncompliance rate existed in block groups where dispensaries were located in relation to schools. The results from the spatial statistics suggest that dispensaries tended to be located near adult businesses that are not considered in existing buffering requirements. Our research allows policymakers to better understand the social and spatial impacts of recreational cannabis distribution to minimize negative effects on residential areas, schools, and other sensitive locations.
Administration of AICAR, an AMPK Activator, Prevents and Reverses Diabetic Polyneuropathy (DPN) by Regulating Mitophagy
Authors: Chandrasekaran Krish , Choi Joungil , Salimian Mohammad , Hedayat Ahmad F. , Russell James W.
Published: December 2024

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes in both Type 1 (T1D) and Type 2 (T2D). While there are no specific medications to prevent or treat DPN, certain strategies can help halt its progression. In T1D, maintaining tight glycemic control through insulin therapy can effectively prevent or delay the onset of DPN. However, in T2D, overall glucose control may only have a moderate impact on DPN, although exercise is clearly beneficial. Unfortunately, optimal exercise may not be feasible for many patients with DPN because of neuropathic foot pain and poor balance. Exercise has several favorable effects on health parameters, including body weight, glycemic control, lipid profile, and blood pressure. We investigated the impact of an exercise mimetic, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), on DPN. AICAR treatment prevented or reversed experimental DPN in mouse models of both T2D and T1D. AICAR in high-fat diet (HFD-fed) mice increased the phosphorylation of AMPK in DRG neuronal extracts, and the ratio of phosphorylated AMPK to total AMPK increased by 3-fold (HFD vs. HFD+AICAR; p < 0.001). Phospho AMP increased the levels of dynamin-related protein 1 (DRP1, a mitochondrial fission marker), increased phosphorylated autophagy activating kinase 1 (ULK1) at Serine-555, and increased microtubule-associated protein light chain 3-II (LC3-II, a marker for autophagosome assembly) by 2-fold. Mitochondria isolated from DRG neurons of HFD-fed had a decrease in ADP-stimulated state 3 respiration (120 ± 20 nmol O2/min in HFD vs. 220 ± 20 nmol O2/min in control diet (CD); p < 0.001. Mitochondria isolated from HFD+AICAR-treated mice had increased state 3 respiration (240 ± 30 nmol O2/min in HFD+AICAR). However, AICAR’s protection in DPN in T2D mice was also mediated by its effects on insulin sensitivity, glucose metabolism, and lipid metabolism. Drugs that enhance AMPK phosphorylation may be beneficial in the treatment of DPN.
Immune Checkpoint Inhibitor-Associated Cutaneous Adverse Events: Mechanisms of Occurrence
Authors: Eshaq Abdulaziz M. , Flanagan Thomas W. , Ba Abbad Abdulqader A. , Makarem Zain Alabden A. , Bokir Mohammed S. , Alasheq Ahmed K. , Al Asheikh Sara A. , Almashhor Abdullah M. , Binyamani Faroq , Al-Amoudi Waleed A. , Bawzir Abdulaziz S. , Haikel Youssef , Megahed Mossad , Hassan Mohamed
Published: December 2024

Immunotherapy, particularly that based on blocking checkpoint proteins in many tumors, including melanoma, Merkel cell carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast (TNB cancer), renal cancer, and gastrointestinal and endometrial neoplasms, is a therapeutic alternative to chemotherapy. Immune checkpoint inhibitor (ICI)-based therapies have the potential to target different pathways leading to the destruction of cancer cells. Although ICIs are an effective treatment strategy for patients with highly immune-infiltrated cancers, the development of different adverse effects including cutaneous adverse effects during and after the treatment with ICIs is common. ICI-associated cutaneous adverse effects include mostly inflammatory and bullous dermatoses, as well as severe cutaneous side reactions such as rash or inflammatory dermatitis encompassing erythema multiforme; lichenoid, eczematous, psoriasiform, and morbilliform lesions; and palmoplantar erythrodysesthesia. The development of immunotherapy-related adverse effects is a consequence of ICIs’ unique molecular action that is mainly mediated by the activation of cytotoxic CD4+/CD8+ T cells. ICI-associated cutaneous disorders are the most prevalent effects induced in response to anti-programmed cell death 1 (PD-1), anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and anti-programmed cell death ligand 1 (PD-L1) agents. Herein, we will elucidate the mechanisms regulating the occurrence of cutaneous adverse effects following treatment with ICIs.
The Role of Mitochondrial Solute Carriers SLC25 in Cancer Metabolic Reprogramming: Current Insights and Future Perspectives
Authors: Ahmed Amer , Iaconisi Giorgia Natalia , Di Molfetta Daria , Coppola Vincenzo , Caponio Antonello , Singh Ansu , Bibi Aasia , Capobianco Loredana , Palmieri Luigi , Dolce Vincenza , Fiermonte Giuseppe
Published: December 2024

Cancer cells undergo remarkable metabolic changes to meet their high energetic and biosynthetic demands. The Warburg effect is the most well-characterized metabolic alteration, driving cancer cells to catabolize glucose through aerobic glycolysis to promote proliferation. Another prominent metabolic hallmark of cancer cells is their increased reliance on glutamine to replenish tricarboxylic acid (TCA) cycle intermediates essential for ATP production, aspartate and fatty acid synthesis, and maintaining redox homeostasis. In this context, mitochondria, which are primarily used to maintain energy homeostasis and support balanced biosynthesis in normal cells, become central organelles for fulfilling the heightened biosynthetic and energetic demands of proliferating cancer cells. Mitochondrial coordination and metabolite exchange with other cellular compartments are crucial. The human SLC25 mitochondrial carrier family, comprising 53 members, plays a pivotal role in transporting TCA intermediates, amino acids, vitamins, nucleotides, and cofactors across the inner mitochondrial membrane, thereby facilitating this cross-talk. Numerous studies have demonstrated that mitochondrial carriers are altered in cancer cells, actively contributing to tumorigenesis. This review comprehensively discusses the role of SLC25 carriers in cancer pathogenesis and metabolic reprogramming based on current experimental evidence. It also highlights the research gaps that need to be addressed in future studies. Understanding the involvement of these carriers in tumorigenesis may provide valuable novel targets for drug development.
Evaluation of Polygenic Risk Score for Prediction of Childhood Onset and Severity of Asthma
Authors: Savelieva Olga , Karunas Alexandra , Prokopenko Inga , Balkhiyarova Zhanna , Gilyazova Irina , Khidiyatova Irina , Khusnutdinova Elza
Published: December 2024

Asthma is a common complex disease with susceptibility defined through an interplay of genetic and environmental factors. Responsiveness to asthma treatment varies between individuals and is largely determined by genetic variability. The polygenic score (PGS) approach enables an individual risk of asthma and respective response to drug therapy. PGS models could help to predict the individual risk of asthma using 26 SNPs of drug pathway genes involved in the metabolism of glucocorticosteroids (GCS), and beta-2-agonists, antihistamines, and antileukotriene drugs associated with the response to asthma treatment within GWAS were built. For PGS, summary statistics from the Trans-National Asthma Genetic Consortium GWAS meta-analysis, and genotype data for 882 individuals with asthma/controls from the Volga-Ural region, were used. The study group was comprised of Russian, Tatar, Bashkir, and mixed ethnicity individuals with asthma (N = 378) aged 2–18 years. and individuals without features of atopic disease (N = 504) aged 4–67 years from the Volga-Ural region. The DNA samples for the study were collected from 2000 to 2021. The drug pathway genes’ PGS revealed a higher odds for childhood asthma risk (p = 2.41 × 10−12). The receiver operating characteristic (ROC) analysis showed an Area Under the Curve, AUC = 0.63. The AUC of average significance for moderate-to-severe and severe asthma was observed (p = 5.7 × 10−9, AUC = 0.64). Asthma drug response pathway gene variant PGS models may contribute to the development of modern approaches to optimise asthma diagnostics and treatment.
RNA Structure: Past, Future, and Gene Therapy Applications
Authors: Haseltine William A. , Hazel Kim , Patarca Roberto
Published: December 2024

First believed to be a simple intermediary between the information encoded in deoxyribonucleic acid and that functionally displayed in proteins, ribonucleic acid (RNA) is now known to have many functions through its abundance and intricate, ubiquitous, diverse, and dynamic structure. About 70–90% of the human genome is transcribed into protein-coding and noncoding RNAs as main determinants along with regulatory sequences of cellular to populational biological diversity. From the nucleotide sequence or primary structure, through Watson–Crick pairing self-folding or secondary structure, to compaction via longer distance Watson–Crick and non-Watson–Crick interactions or tertiary structure, and interactions with RNA or other biopolymers or quaternary structure, or with metabolites and biomolecules or quinary structure, RNA structure plays a critical role in RNA’s lifecycle from transcription to decay and many cellular processes. In contrast to the success of 3-dimensional protein structure prediction using AlphaFold, RNA tertiary and beyond structures prediction remains challenging. However, approaches involving machine learning and artificial intelligence, sequencing of RNA and its modifications, and structural analyses at the single-cell and intact tissue levels, among others, provide an optimistic outlook for the continued development and refinement of RNA-based applications. Here, we highlight those in gene therapy.
Direct Vascular Effects of Angiotensin II (A Systematic Short Review)
Authors: Nádasy György L. , Balla András , Dörnyei Gabriella , Hunyady László , Szekeres Mária
Published: December 2024

The octapeptide angiotensin II (Ang II) is a circulating hormone as well as a locally formed agonist synthesized by the angiotensin-converting enzyme (ACE) of endothelial cells. It forms a powerful mechanism to control the amount and pressure of body fluids. All main effects are directed to save body salt and water and ensure blood pressure under basic conditions and in emergencies. All blood vessels respond to stimulation by Ang II; the immediate response is smooth muscle contraction, increasing vascular resistance, and elevating blood pressure. Such effects are conveyed by type 1 angiotensin receptors (AT1Rs) located in the plasma membrane of both endothelial and vascular smooth muscle cells. AT1Rs are heterotrimeric G protein-coupled receptors (GPCRs), but their signal pathways are much more complicated than other GPCRs. In addition to Gq/11, the G12/13, JAK/STAT, Jnk, MAPK, and ERK 1/2, and arrestin-dependent and -independent pathways are activated because of the promiscuous attachment of different signal proteins to the intracellular G protein binding site and to the intracellular C terminal loop. Substantial changes in protein expression follow, including the intracellular inflammation signal protein NF-κB, endothelial contact proteins, cytokines, matrix metalloproteinases (MMPs), and type I protocollagen, eliciting the inflammatory transformation of endothelial and vascular smooth muscle cells and fibrosis. Ang II is an important contributor to vascular pathologies in hypertensive, atherosclerotic, and aneurysmal vascular wall remodeling. Such direct vascular effects are reviewed. In addition to reducing blood pressure, AT1R antagonists and ACE inhibitors have a beneficial effect on the vascular wall by inhibiting pathological wall remodeling.