bluuebunny/crossref_metadata_2025_split huggingface dataset:
The diversity of AMPA receptor inhibition mechanisms among amidine-containing compounds
Authors: Zhigulin Arseniy S. , Dron Mikhail Y. , Barygin Oleg I. , Tikhonov Denis B. 
Published: October 2024

Amidine-containing compounds are primarily known as antiprotozoal agents (pentamidine, diminazene, furamidine) or as serine protease inhibitors (nafamostat, sepimostat, camostat, gabexate). DAPI is widely recognized as a fluorescent DNA stain. Recently, it has been shown that these compounds also act as NMDA receptor inhibitors. In this study, we examined the activity of these compounds and analyzed the mechanisms of action in relation to another important class of ionotropic glutamate receptors–calcium-permeable AMPA receptors (CP-AMPARs) and calcium-impermeable AMPA receptors (CI-AMPARs) – using the whole-cell patch-clamp method on isolated male Wistar rat brain neurons. Gabexate and camostat were found to be inactive. Other compounds preferentially inhibited calcium-permeable AMPA receptors with IC50 values of 30–60 µM. DAPI and furamidine were also active against CI-AMPARs with IC50s of 50–60 μM, while others showed poor activity. All active compounds acted as channel blockers, which are able for permeating into the cytoplasm on both CP- and CI-AMPARs. Specifically, sepimostat showed trapping in the closed CP-AMPAR channel. Furamidine and DAPI demonstrated a voltage-independent action on CI-AMPARs, indicating binding to an additional superficial site. While the majority of compounds inhibited glutamate-activated steady-state currents as well as kainate-activated currents on CI-AMPARs, pentamidine significantly potentiated glutamate-induced steady-state responses. The potentiating effect of pentamidine resembles the action of the positive allosteric modulator cyclothiazide although the exact binding site remains unclear. Thus, this study, together with our previous research on NMDA receptors, provides a comprehensive overview of this novel group of ionotropic glutamate receptors inhibitors with a complex pharmacological profile, remarkable diversity of effects and mechanisms of action.
Fentanyl enhances immune cell response through TLR4/MD-2 complex
Authors: Chemello Chiara , Facci Laura , Marcolin Emma , Ramaschi Giovanni Eugenio , Barbierato Massimo , Giusti Pietro , Bolego Chiara , Zusso Morena 
Published: October 2024

IntroductionOpioids have been shown to induce neuroinflammation and immune cell activation, that might contribute to some of the opioid side effects, such as opioid-induced tolerance and paradoxical hyperalgesia. In this context, TLR4/MD-2 complex has been proposed as an off-target site for opioid action. This study was aimed at investigating the effect of fentanyl on lipopolysaccharide (LPS)-induced TLR4/MD-2 activation in rat primary microglia and human monocyte-derived macrophages (MDM).Materials and MethodsThe effect of fentanyl was first explored by measuring the expression and release of different proinflammatory mediators in primary rat microglia and human MDM by real-time PCR and ELISA. Then, the involvement of TLR4/MD-2 signaling was investigated studying NF-κB activation in HEK293 cells stably transfected with human TLR4, MD-2, and CD14 genes (HEK-Blue hTLR4 cells) and in human MDM.ResultsFentanyl increased mRNA levels, as well as the LPS-induced secretion of proinflammatory mediators in primary microglia and MDM. Two inhibitors of TLR4/MD-2 signaling, namely the oxazoline derivative of N-palmitoylethanolamine (PEA-OXA) and CLI-095, blocked the production and release of proinflammatory cytokines by microglia stimulated with LPS and fentanyl, suggesting that TLR4/MD-2 could be the target of the proinflammatory activity of fentanyl. Finally, we showed that fentanyl in combination with LPS activated NF-κB signaling in human MDM and in HEK-Blue hTLR4 cells and this effect was blocked by inhibitors of TLR4/MD-2 complex.DiscussionThese results provide new insight into the mechanism of the proinflammatory activity of fentanyl, which involves the activation of TLR4/MD-2 signaling. Our findings might facilitate the development of novel inhibitors of TLR4/MD-2 signaling to combine with opioid-based analgesics for effective and safe pain management.
Exaggerated postnatal surge of orexin neurons and the effects of elimination of excess orexin on blood pressure and exaggerated chemoreflex in spontaneously hypertensive rats
Authors: Lusk Savannah , Moushey Alexander M. , Iwakoshi Nicholas , Wilson Christopher G. , Li Aihua , Ray Russell 
Published: October 2024

An overactive orexin (OX) system is associated with neurogenic hypertension and an exaggerated chemoreflex in spontaneously hypertensive rats (SHRs). However, the chronology and mechanism of this association is unclear. We hypothesized that increased postnatal neurogenesis of OX neurons in SHRs precedes and contributes to the aberrant increase in mean arterial blood pressure (MAP) and the exaggerated response to hypercapnia during postnatal development. Using immunohistochemical methods and bromodeoxyuridine, we mapped the timeline of orexin neuron neurogenesis and maturation during early postnatal development. We then used whole-body plethysmography with EEG and EMG to map the development of mean arterial pressure (MAP) and state regulation. Finally, we used OX-targeted saporin toxin to determine the effects of eliminating excess OX neurons on the elevated MAP and exaggerated chemoreflex in adult SHRs. We found that both SHRs and Wistar–Kyoto (WKY) rats experienced postnatal increases in OX neurons. However, SHRs experienced a greater increase than WKY rats before P15, which led to significantly more OX neurons in SHRs than age-matched WKY controls by P15–16 (3,720 ± 780 vs. 2,406 ± 363, p = 0.005). We found that neurogenesis, as evidenced by BrdU staining in OX-positive neurons, was the primary contributor to the excess OX neurons in SHRs during early postnatal development. While SHRs develop more OX neurons by P15–16, SHRs and normotensive WKY control rats have similar MAP during postnatal development until P25 in wakefulness (81.6 ± 6.6 vs. 67.5 ± 6.8 mmHg, p = 0.006) and sleep (79.3 ± 6.1 vs. 66.6 ± 6.5, p = 0.009), about 10 days after the surge of OX neurons. By selectively eliminating excess (∼30%) OX neurons in SHRs, we saw a significantly lowered MAP and hypercapnic ventilatory chemoreflex compared to non–lesioned SHRs at P40. Additionally, we found unique signatures in state indicative of the attention defecit phenotype commonly associated with this model. We suggest that the postnatal increase of OX neurons, primarily attributed to exaggerated postnatal OX neurogenesis, may be necessary for the development of higher MAP and exaggerated chemoreflex in SHRs, and modulation of the overactive OX system may have a potential therapeutic effect during the pre-hypertensive period.
Comparative metabolomic analysis of spaghetti meat and wooden breast in broiler chickens: unveiling similarities and dissimilarities
Authors: Choi Janghan , Shakeri Majid , Kim Woo Kyun , Kong Byungwhi , Bowker Brian , Zhuang Hong 
Published: October 2024

IntroductionSpaghetti meat (SM) and wooden breast (WB) are emerging myopathies in the breast meat of fast-growing broiler chickens. The purpose of the study was to investigate the metabolomic differences between normal (N), SM, and WB fillets 24 h postmortem.Materials and methodsEight chicken breasts for each experimental group were collected from a commercial processing plant. Supernatant from tissue homogenates were subjected to ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS) analysis.Results and methodsA total of 3,090 metabolites were identified in the chicken breast meat. The comparison of WB and N showed 850 differential metabolites (P &lt; 0.05), and the comparison of SM and N displayed 617 differential metabolites. The comparison of WB and SM showed 568 differential metabolites. The principal component analysis (PCA) plots showed a distinct separation between SM and N and between WB and N except for one sample, but SM and WB were not distinctly separated. Compared to N, 15-Hydroxyeicosatetraenoic acid (15-HETE) increased, and D-inositol-4-phosphate decreased in both SM and WB, indicating that cellular homeostasis and lipid metabolism can be affected in SM and WB. The abundance of nicotinamide adenine dinucleotide (NAD) + hydrogen (H) (NADH) was exclusively decreased between SM and N (P &lt; 0.05). Purine metabolism was upregulated in SM and WB compared to N with a greater degree of upregulation in WB than SM. Folic acid levels decreased in SM and WB compared to N (P &lt; 0.05). Steroid hormone biosynthesis was downregulated in SM compared to N (P &lt; 0.05). Carbon metabolism was downregulated in SM and WB compared to N with greater degree of downregulation in WB than SM (P &lt; 0.05). These data suggest both shared and unique metabolic alterations in SM and WB, indicating commonalities and differences in their underlying etiologies and meat quality traits. Dietary supplementation of deficient nutrients, such as NADH, folic acids, etc. and modulation of altered pathways in SM and WB would be strategies to reduce the incidence and severity of SM and WB.
Physiological and metabolomic analyses reveal the mechanism by which exogenous spermine improves drought resistance in alfalfa leaves (Medicago sativa L.)
Authors: Wang Wenjuan , Kang Wenjuan , Shi Shangli , Liu Linbo 
Published: October 2024

IntroductionAlfalfa (Medicago sativa L.) is a globally important legume crop with high nutritional and ecological value. Drought poses a serious threat to alfalfa acreage and yields. Spermine (Spm) has been shown to protect plants from drought damage. The aim of this study was to clarify the mechanism of exogenous Spm to improve drought resistance of alfalfa. MethodsIn this study, we root applied 0.1, 0.5, and 1 mM Spm to Gannong No. 3 (G3) alfalfa under drought stress, and then determined their physiological and metabolic changes. ResultsThe results showed that exogenous Spm increased chlorophyll content, chlorophyll fluorescence parameters and gas exchange parameters, enhanced antioxidant enzymes activity, improved ascorbic acid-glutathione (AsA-GSH) cycle, increased osmoregulatory substances content, reduced hydrogen peroxide and superoxide anion levels, and inhibited malondialdehyde accumulation in alfalfa under drought stress, thereby increasing plant height and leaf relative water content and enhancing drought tolerance of alfalfa. The redundancy analysis of the above physiological indicators showed that the addition of the optimal Spm to improve drought tolerance of alfalfa under drought stress was mainly achieved by increasing catalase activity and improving the ASA-GSH cycle. In addition, metabolomics analysis revealed that exogenous Spm increased the content of oxobutanedioic acid, citric acid, fumaric acid and malic acid to enhance the tricarboxylic acid cycle. Meanwhile, exogenous Spm increased endogenous Spm and proline (Pro) content to resist drought stress by enhancing Spm and Pro metabolism. Moreover, exogenous Spm increased the accumulation of the signaling substance abscisic acid. DiscussionIn conclusion, exogenous Spm enhanced drought resistance of alfalfa leaves under drought stress.
Effects of short-form video app addiction on academic anxiety and academic engagement: The mediating role of mindfulness
Authors: Li Gongyu , Geng Yaxuan , Wu Tingting 
Published: October 2024

IntroductionThe impact of short-form video app addiction on academic performance, including academic anxiety and engagement, has not been adequately explored or addressed.MethodThis study tested the effects of short-form video app addiction on academic anxiety and academic engagement and the mediating role of mindfulness in these relationships. The participants were 1,879 undergraduates in China who completed the Short-Form Video App Addiction Scale, Mindful Attention Awareness Scale, Academic Anxiety Sub-questionnaire of Academic Emotions Questionnaire, and Engagement Scales. Structural equation modelling (SEM) was used to analyse the data.ResultsThe results indicate that short-form video app addiction has significant positive effects on academic anxiety and negative effects on academic engagement. Furthermore, short-form video app addiction has significant indirect effects on academic anxiety and engagement via mindfulness. The proportions of the mediation effects are 19.23 and 51.85%, respectively.DiscussionThe implications and limitations of this study are discussed.
Personal views of aging in midlife and older age: the role of personality
Authors: Carbone Elena , Sella Enrico , Signori Diletta , Borella Erika 
Published: October 2024

IntroductionPersonal views of aging (VoA) reflect individuals’ perceptions, attitudes, and expectations regarding their aging selves. The present cross-sectional study was aimed at examining whether personality traits, as defined by the Big Five model, are associated with different VoA concepts related to both subjective age and awareness of age-related gains and losses in midlife and older age.Materials and methodsA sample of 224 participants aged 46–85 years reported their felt age and completed the Awareness of Age-Related Change (AARC) questionnaire, assessing perceptions of age-related gains (AARC-Gains) and losses (AARC-Losses) in various functioning domains, as well as the short version of the Big Five Inventory.ResultsLinear regression models showed that Openness contributed to explain youthful subjective age. Extraversion explained higher AARC-Gains scores, whereas Emotional Stability, along with younger chronological age and perceiving better self-rated health, contributed to explaining lower AARC-Losses scores.DiscussionThese findings confirm the relationship between personality traits and personal VoA. They further suggest that such an association varies depending on the VoA measure considered. They underscore the importance of considering personality among those individual characteristics capable of shaping personal VoA, with implications for the development of tailored interventions and the understanding of the underlying mechanisms linking personal VoA to health and longevity outcomes in midlife and older age.
The effect of exercise motivation on college students’ self-efficacy: the mediating roles of leisure satisfaction and mental toughness
Authors: Yu Chengfeng , Zeng Zhaohong , Xue Aochuan , Wu Qianjin 
Published: October 2024

BackgroundThe theory of motivation suggests that individual motivation is moderately stimulated to drive individuals to engage in the behaviors for which they are motivated. It is therefore that the moderate stimulation of exercise motivation will likely lead to the enhancement of college students’ participation in exercise.ObjectiveInvestigate the effect of exercise motivation on college students’ self-efficacy, reveal the mediating role of leisure satisfaction and mental toughness, and provide empirical evidence improving college students’ self-efficacy through exercise motivation.MethodsA stratified whole-sample approach was employed to survey 715 college students, based on a correlation table with good reliability and validity. Scale items were designed to collect subjects’ exercise motivation, self-efficacy, leisure satisfaction, and mental toughness in the study context. Mediation effect analyses were carried out using SPSS and AMOS.Results and conclusionA significant positive effect of exercise motivation on self-efficacy (β = 0.18, p &lt; 0.001), leisure satisfaction (β = 0.50, p &lt; 0.001), and mental toughness (β = 0.45, p &lt; 0.001). Leisure satisfaction and mental toughness had a significant positive effect on self-efficacy (β = 0.40, p &lt; 0.001; β = 0.30, p &lt; 0.001). Furthermore, leisure satisfaction and mental toughness significantly mediated in exercise motivation and self-efficacy. In conclusion, our findings further explored the effects of exercise motivation on college students’ self-efficacy and revealed the mediating roles of leisure satisfaction and mental toughness.
The aftermath of COVID-19: generalized anxiety disorder and burnout among radiology practitioners and interns in Saudi Arabia
Authors: Alshamrani Khalid M. , Alkenawi Abdulkader A. , Falatah Hebah A. , Alsulami Waad , Alzahrani Faisal A. , Nayta Tariq M. , Alharbi Abdulrahman H. , Alzahrani Mohannad A. , Almutairi Rahaf H. , Alshomrani Bander S. , Tasslaq Sameer E. , Aldhebaib Ali M. 
Published: October 2024

BackgroundThe coronavirus disease (COVID-19) pandemic has presented unprecedented stressors and difficulties for healthcare professionals. This study explored the prevalence of generalized anxiety disorders and burnout among radiology practitioners and interns in various hospitals in Saudi Arabia after the end of the COVID-19 global public health emergency.MethodsA cross-sectional survey of 230 radiology practitioners and interns was conducted between October and November 2023. This study utilized the Generalized Anxiety Disorder 7-item (GAD-7) scale and Maslach Burnout Inventory-Human Services Survey for Medical Personnel (MBI-HSS-MP) 22-item questionnaire, employing a non-probability convenience sampling method. The average scores of the individual components constituting the GAD-7 scale and each burnout scale were calculated, and statistical analyses were conducted using the Mann-Whitney U and Kruskal-Wallis H nonparametric tests.ResultsOf 382 radiology practitioners and interns, 230 (60.2%) responded to the survey. Notably, 42.6% of the participants reported experiencing GAD. Regarding burnout, 82.3% were at moderate-to-high risk for emotional exhaustion, 93.5% for depersonalization, and 52.1% for personal achievement. The 31–40 years age group showed significantly higher burnout rates (p = 0.001) compared with the other age groups. Those with more than three years of experience had notably higher emotional exhaustion scores (p = 0.002) and a nearly significant increase in depersonalization scores (p = 0.051) than those with less experience.DiscussionOur study revealed that 42.6% of radiology practitioners and interns experienced GAD, with the majority facing significant burnout. Furthermore, our research indicates a decline in GAD levels among radiology practitioners and interns compared with the peak COVID-19 pandemic period. It also showed a significant increase in both the incidence and severity of burnout, surpassing pre-pandemic levels in a comparable cohort. These findings emphasize the pressing challenges of GAD and burnout among healthcare workers, especially radiology professionals.
Prevalence of sleep disturbances in endometriosis patients: a systematic review and meta-analysis
Authors: Zhang Yujie , Liu Hui , Feng Chaochen , Yang Yadi , Cui Liwei 
Published: October 2024

ObjectiveThis study systematically analyzes the prevalence of sleep disturbance in patients with endometriosis.MethodsThe PubMed, Web of Science, Embase, Wanfang, China National Knowledge Internet Database (CNKI), China Science and Technology Journal Database were searched from their establishment to January 2024, using the search terms endometriosis and sleep disturbance to collect relevant literature on the prevalence of sleep disturbance in patients with endometriosis. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias. The prevalence of sleep disorders in patients with endometriosis was systematically analyzed using Stata17.0 software.ResultsSixteen studies with 2573 participants were included. The prevalence of sleep disturbance in patients with endometriosis was 70.8% (95% confidence interval: 60.7%~80.9%). The said prevalence was higher in China than in Iran and the European countries (78.2 vs. 57.6 vs. 64.4, Q=9.27, P=0.010) and increased significantly since 2018 (79.0 vs. 61.3, Q=3.97, P=0.046). This prevalence was significantly higher in the cohort study than that in cross-sectional and case-control studies (84.0 vs. 74.0 vs. 59.5, Q=7.16, P=0.028).ConclusionThe prevalence of sleep disturbance is high in patients with endometriosis, particularly in China and its prevalence has increased significantly in recent years. Appropriate interventions are recommended to effectively prevent or minimize sleep disturbances in patients with endometriosis.
Role of health literacy on lifestyle and glycemic control among women with diabetes during pregnancy: a cross-sectional study
Authors: Babazadeh Towhid , Pourrazavi Sara , Ardeshiri Zahra , Nadi Akbar , Chollou Khalil Maleki 
Published: October 2024

BackgroundThe present study aimed to explore the impact of health literacy on the lifestyle of women with diabetes during pregnancy.MethodsA cross-sectional study assessed the influence of some demographic characteristics and health literacy dimensions in predicting lifestyle and glycemic control in a sample of 230 women with diabetes during pregnancy. The data collection included a demographic form, a health literacy scale, and a lifestyle questionnaire. The data were analyzed using a one-way ANOVA and Pearson’s correlation coefficient. The predictors were determined using a hierarchical linear regression analysis.ResultsThe participants had an average age of 27.74 years (SD = 6.54) and an average HbA1c level of 6.93% (SD = 1.93). Approximately 51.0% of the variation in lifestyle can be explained by health literacy (HL) and demographic variables (p-value &lt;0.05). In addition, approximately 15.0% of the variation in HbA1c can be explained by health literacy, lifestyle, and demographic variables (p-value &lt;0.05).FindingsAccording to our findings, decision-making was found to be the strongest predictor of lifestyle. This study provides valuable information for nurses and other healthcare providers to help empower pregnant women to increase their health literacy and improve their lifestyle.
The leading causes of death in the US and Mexico’s pediatric population are related to violence: a note on secondary analyses of registered deaths from 2000 to 2022
Authors: Castilla-Peon Maria F. , Rendón Pablo L. , Gonzalez-Garcia Nadia 
Published: October 2024

Introductionour objective was to analyze the trends in the leading causes of death among the pediatric population aged 1–19 years in Mexico and the United States (US) from 2000 to 2022. Methods. Data for Mexico were sourced from the National Institute of Statistics and Geography (INEGI), while the US data were extracted from the Centers for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (CDC-WONDER) databases.ResultsHomicide has been the leading cause of death since 2017 in Mexico and since 2019 in US youths aged 1–19. In Mexico, it reached 6.5 deaths per 100,000 people in 2022. Despite the overall pediatric mortality decline from 2000 to 2022 in both countries, the pediatric homicide rate has increased by 93.3 and 35.8% In Mexico and the US, respectively, and suicide by 86.6 and 36.9%. In both countries, death by firearm-related injuries had risen in a parallel sense. In the US, deaths by drug overdose and poisoning have increased by 314.8%.ConclusionDespite advancements in infant healthcare over the past two decades in Mexico, there remains a significant gap in the provision of healthcare services to the adolescent population. Addressing issues related to violence, mental health, and substance abuse through targeted public policies is imperative for both Mexico and the US, especially given their shared border region.