bluuebunny/crossref_metadata_2025 huggingface dataset:
Laser-Induced Graphene Electrodes for Flexible pH Sensors
Authors: Massaglia Giulia , Spisni Giacomo , Serra Tommaso , Quaglio Marzia
Published: December 2024

In the growing field of personalized medicine, non-invasive wearable devices and sensors are valuable diagnostic tools for the real-time monitoring of physiological and biokinetic signals. Among all the possible multiple (bio)-entities, pH is important in defining health-related biological information, since its variations or alterations can be considered the cause or the effect of disease and disfunction within a biological system. In this work, an innovative (bio)-electrochemical flexible pH sensor was proposed by realizing three electrodes (working, reference, and counter) directly on a polyimide (Kapton) sheet through the implementation of CO2 laser writing, which locally converts the polymeric sheet into a laser-induced graphene material (LIG electrodes), preserving inherent mechanical flexibility of Kapton. A uniform distribution of nanostructured PEDOT:PSS was deposited via ultrasonic spray coating onto an LIG working electrode as the active material for pH sensing. With a pH-sensitive PEDOT coating, this flexible sensor showed good sensitivity defined through a linear Nernstian slope of (75.6 ± 9.1) mV/pH, across a pH range from 1 to 7. We demonstrated the capability to use this flexible pH sensor during dynamic experiments, and thus concluded that this device was suitable to guarantee an immediate response and good repeatability by measuring the same OCP values in correspondence with the same pH applied.
Carbapenem-Resistant E. coli Adherence to Magnetic Nanoparticles
Authors: Caliskan-Aydogan Oznur , Zaborney Kline Chloe , Alocilja Evangelyn C.
Published: December 2024

Carbapenem-resistant Enterobacterales (CRE) is an emerging global concern. Specifically, carbapenemase-producing (CP) E. coli strains in CRE have recently been found in clinical, environmental, and food samples worldwide, causing many hospitalizations and deaths. Their rapid identification and characterization are paramount in control, management options, and treatment choices. Thus, this study aimed to characterize the cell surface properties of carbapenem-resistant (R) E. coli isolates and their interaction with glycan-coated magnetic nanoparticles (gMNPs) compared with carbapenem-susceptible (S) E coli. This study used two groups of bacteria: The first group included E. coli (R) isolates harboring carbapenemases and had no antibiotic exposure. Their initial gMNP–cell binding capacity, with cell surface characteristics, was assessed. In the second group, one of the E. coli (R) isolates and E. coli (S) had long-term serial antibiotic exposure, which we used to observe their cell surface characteristics and gMNP interactions. Initially, cell surface characteristics (cell morphology and cell surface charge) of the E. coli isolates were evaluated using confocal laser scanning microscope (LSCM) and a Zetasizer, respectively. The interaction of gMNPs with the E. coli isolates was assessed through LSCM and transmission electron microscope (TEM). Further, the gMNP–cell attachment was quantified as a concentration factor (CF) through the standard plating method. The results showed that the CF values of all E. coli (R) were significantly different from those of E. coli (S), which could be due to the differences in cell characteristics. The E. coli (R) isolates displayed heterogeneous cell shapes (rod and round cells) and lower negative zeta potential (cell surface charge) values compared to E. coli (S). Further, this research identified the differences in the cell surface characteristics of E. coli (S) under carbapenem exposure, compared to unexposed E. coli (S) that impact their attachment capacity. The gMNPs captured more E. coli (S) cells compared to carbapenem-exposed E. coli (S) and all E. coli (R) isolates. This study clearly found that differences in cell surface characteristics impact their interaction with magnetic nanoparticles. The gained insights aid in further understanding adhesion mechanisms to develop or improve bacterial isolation techniques and diagnostic and treatment methods for CRE.
Pleozymes: Pleiotropic Oxidized Carbon Nanozymes Enhance Cellular Metabolic Flexibility
Authors: Vo Anh T. T. , Mouli Karthik , Liopo Anton V. , Lorenzi Philip , Tan Lin , Wei Bo , Martinez Sara A. , McHugh Emily A. , Tour James M. , Khan Uffaf , Derry Paul J. , Kent Thomas A.
Published: December 2024

Our group has synthesized a pleiotropic synthetic nanozyme redox mediator we term a “pleozyme” that displays multiple enzymatic characteristics, including acting as a superoxide dismutase mimetic, oxidizing NADH to NAD+, and oxidizing H2S to polysulfides and thiosulfate. Benefits have been seen in acute and chronic neurological disease models. The molecule is sourced from coconut-derived activated charcoal that has undergone harsh oxidization with fuming nitric acid, which alters the structure and chemical characteristics, yielding 3–8 nm discs with broad redox potential. Prior work showed pleozymes localize to mitochondria and increase oxidative phosphorylation and glycolysis. Here, we measured cellular NAD+ and NADH levels after pleozyme treatment and observed increased total cellular NADH levels but not total NAD+ levels. A 13C-glucose metabolic flux analysis suggested pleozymes stimulate the generation of pyruvate and lactate glycolytically and from the tricarboxylic acid (TCA) cycle, pointing to malate decarboxylation. Analysis of intracellular fatty acid abundances suggests pleozymes increased fatty acid β-oxidation, with a concomitant increase in succinyl- and acetyl-CoA. Pleozymes increased total ATP, potentially via flexible enhancement of NAD+-dependent catabolic pathways such as glycolysis, fatty acid β-oxidation, and metabolic flux through the TCA cycle. These effects may be favorable for pathologies that compromise metabolism such as brain injury.
Numerical Study on the Static Bending Response of Cracked Wind Turbine Blades Reinforced with Graphene Platelets
Authors: Kim Hyeong Jin , Cho Jin-Rae
Published: December 2024

With the growing demand for wind energy, the development of advanced materials for wind turbine support structures and blades has garnered significant attention in both industry and academia. In previous research, the authors investigated the incorporation of graphene platelets (GPLs) into wind turbine blades, focusing on the structural performance and cost-effectiveness relative to conventional fiberglass composites. These studies successfully demonstrated the potential advantages of GPL reinforcement in improving blade performance and reducing the blade’s weight and costs. Building upon prior work, the present study conducts a detailed investigation into the static bending behavior of GPL-reinforced wind turbine blades, specifically examining the impact of crack location and length. A finite element model of the SNL 61.5 m wind turbine blade was rigorously developed and validated through comparison with the existing literature to ensure its accuracy. Comprehensive parametric analyses were performed to assess deflection under various crack lengths and positions, considering both flapwise and edgewise bending deformations. The findings indicate that GPL-reinforced blades exhibit reduced sensitivity to crack propagation compared to traditional fiberglass blades. Furthermore, the paper presents a thorough parametric analysis of the effects of crack location and length on blade performance.
Planetary Health Diet for Childhood Obesity Prevention: Integrating Nutritional Health with Environmental Stewardship
Authors: Conti Maria Vittoria , Vincenti Alessandra , Beretta Alice , Calcaterra Valeria , Taranto Silvia , Diotti Marianna , Zuccotti Gianvincenzo , Cena Hellas
Published: December 2024

Background: Childhood obesity is a critical public health challenge with a rising prevalence worldwide, contributing to numerous health risks and long-term societal burdens. Concurrently, climate change and environmental degradation demand sustainable approaches to dietary patterns. The Planetary Health Diet (PHD), initially designed for adults, emphasizes plant-based foods and sustainable practices. Objectives: This review explores the suitability of the PHD for addressing childhood obesity by assessing its nutritional adequacy and proposing necessary adaptations for pediatric populations. Methods: A narrative review methodology was employed, examining data from global and regional nutritional guidelines and evaluating the PHD’s bromatological composition against age-specific requirements. Results: The findings indicate that while the PHD aligns with environmental goals, it may not fully meet the energy and specific nutrient needs of children and adolescents without modifications. Key challenges include ensuring adequate intake of bioavailable protein, iron, calcium, vitamin B12, and vitamin D. Strategies such as incorporating fortified foods, optimizing food pairings, and gradual adaptation to high-fiber diets are critical for successful implementation. This review also highlights the importance of cultural adaptability, family involvement, and regional food systems in promoting adherence. Tailored interventions, such as school meal programs and educational initiatives, can bridge gaps in nutrition while fostering sustainable dietary behaviors. Conclusions: Adapting the PHD for pediatric needs presents an opportunity to integrate nutritional health with environmental stewardship, contributing to obesity prevention and a sustainable future. Further research is required to validate these adaptations and develop comprehensive frameworks for global implementation.
Small Intestinal Bacterial Overgrowth and Childhood Malnutrition: A Comprehensive Review of Available Evidence
Authors: Mareș Cristina Roxana , Săsăran Maria Oana , Mărginean Cristina Oana
Published: December 2024

The gut microbiome is essential for children’s normal growth and development, with its formation aligning closely with key stages of growth. Factors like birth method, feeding practices, and antibiotic exposure significantly shape the composition and functionality of the infant gut microbiome. Small intestinal bacterial overgrowth (SIBO) involves an abnormal increase in bacteria within the small intestine. This overgrowth can interfere with digestion, impair nutrient absorption, and lead to both local and systemic inflammation, potentially contributing to malnutrition. In this review, we provide a comprehensive overview of the current understanding of the relationship between SIBO and malnutrition, with a particular focus on the pediatric population. SIBO seems to play an important role in nutrient malabsorption through the gut microbiome imbalance, local inflammation, and disruption of the mucosal intestinal barrier. Additionally, SIBO is more prevalent in digestive disorders linked to malabsorption and malnutrition. Different therapeutic strategies for addressing malnutrition-related SIBO have been proposed. While antibiotics are the primary treatment for SIBO, their effectiveness in promoting weight gain among malnourished children remains uncertain. Hence, future research directed at the impact of microbiome imbalance on nutrient intake and absorption could bring to light new strategies for the effective prevention and treatment of malnutrition.
Study of the Association Between Diets Containing Nuts and Seeds and the Degree of Abdominal Aortic Calcification
Authors: Tucker Larry A.
Published: December 2024

Background: The association between nuts and seeds (nuts/seeds) consumption and abdominal aortic calcification (AAC) has been studied rarely, if at all. However, AAC is a good marker of CVD risk and premature mortality. Consequently, the present observational study was conducted. It had two primary purposes: (1) to determine the relationship between the consumption of nuts/seeds and AAC, and (2) to examine the effects of nine potential confounding variables on the relationship between nuts/seeds consumption and AAC. Methods: The sample included 2611 randomly selected adults representative of the United States population. Data were collected as part of the National Health and Nutrition Examination Survey (NHANES). The outcome measure was AAC, divided into three categories: none, mild, and moderate/severe. Total consumption of nuts/seeds was assessed utilizing the mean of two diet recall assessments. Results: There was an inverse dose–response relationship between categories of nuts/seeds consumption and AAC, with age, sex, and race controlled (F = 6.4, p = 0.0233). After controlling for the demographic variables and physical activity, hypertension status, waist circumference, diabetes status, and smoking, the relationship between nuts/seeds and AAC was minimally affected (F = 6.0, p = 0.0268). Conclusions: In conclusion, nuts/seeds consumption appears to differentiate among adults with different levels of AAC. Control of many covariates had little impact on the associations. The recommendations of the U.S. Dietary Guidelines (2020–2025) that encourage the eating of nuts/seeds are supported by the results of this investigation.
Dietary Patterns, Serum BDNF and Fatty Acid Profiles in Physically Active Male Young Adults: A Cluster Analysis Study
Authors: Johne Monika , Maculewicz Ewelina , Mastalerz Andrzej , Białek Małgorzata , Wojtak Wiktoria , Osuch Bartosz , Majewska Małgorzata , Czauderna Marian , Białek Agnieszka
Published: December 2024

Background/Objectives: Although physical activity and balanced diet may increase peripheral brain-derived neurotrophic factor (BDNF) concentration, little is known about whether these factors modify BDNF content in physically active individuals and whether the serum fatty acid (FA) profile is related. This study aimed to evaluate quality of diet, identify specific dietary patterns and assess their influence on BDNF and FA levels in serum. It is hypothesized that there is a correlation between diet quality and the concentrations of BDNF and FA in the serum of physically active male individuals. Methods: Physically active young adult male students at Jozef Pilsudski University of Physical Education in Warsaw (Poland) were enrolled. Dietary patterns were identified with cluster analysis and linear discriminant analysis (LDA) based on responses to a validated food frequency questionnaire, KomPAN® version 1.1. Results: Consumption of beverages, vegetables, milk, wholemeal bread/rolls, fruit and vegetable juices, butter, tinned vegetables and fruits were significant in the LDA model, in which three clusters were distinguished. Cluster 1 was characterized by more frequent consumption of wholemeal bread/rolls, milk, fruits, vegetables, fruit and vegetable juices and sweetened hot beverages and by significantly greater values for the pro-healthy diet index (p < 0.0001) and diet quality index (p < 0.0001) compared to Clusters 2 and 3. The diet of Cluster 2 was of the worst quality, as indicated by the higher values of the not-healthy diet index. Cluster 1 had the tendency for the highest BDNF levels (of the best quality of diet), and a tendency for decreased BDNF concentration with an increased physical activity level was observed. Conclusions: Physical activity, diet quality and BDNF level depend, correlate and interact with each other to provide both optimal physical and mental health.
Food Addiction: Prevalence, Severity, and Impact on Vascular Stroke Risk Factors in a French Hospital-Based Sample
Authors: Seelarbokus Bibi Aliya , Rabat Yolaine , Lalanne Christophe , Sibon Igor , Berthoz Sylvie
Published: December 2024

Background: Stroke ranks as the second leading cause of death and the third leading cause of disability in adults worldwide. While an unhealthy diet is an independent risk factor for stroke, its association with disordered eating behaviours on stroke remains overlooked. This exploratory study aimed to evaluate the prevalence and severity of addictive-like eating behaviours in stroke patients and their association with the main vascular stroke risk factors. Methods: First-ever minor or moderate stroke patients with the ability to complete self-report questionnaires were included. Addictive-like eating was assessed using the Yale Food Addiction Scale 2.0 (YFAS 2.0). The variables of interest were: (i) the proportion of patients meeting the diagnosis of food addiction (FA); (ii) FA symptoms count and severity; (iii) addictive-like eating profile severity. Their association with four main vascular risk factors (obesity, hypertension, dyslipidemia and diabetes) were tested using univariate and multivariate analyses. Results: Over a 4-month period, 101 patients (mean (standard deviation (SD)), 62.8 (13.7) years; males: 60.4%) were consecutively screened with the YFAS 2.0. Overall, 5% of the sample endorsed an FA diagnosis, and 38.6% screened positive for at least one of the symptom criteria, with the most frequently endorsed symptom being “Inability to cut down”. Dyslipidemia was the only vascular risk factor associated with the FA diagnosis (p = 0.043, 95% CI [−0.21; 0.01]). However, the severity of the addictive profile was associated with dyslipidemia (p = 0.016, 95% CI [−2.16; −0.21]) and diabetes (p = 0.038, 95% CI [−1.77; 0.25]), but only independently with dyslipidemia (p = 0.05; OR = 1.25; 95% CI [1.00; 1.56]). There were significant associations between the number of vascular risk factors and the severity of Time spent, Tolerance, and Use despite adverse consequences of FA symptoms, both in univariate and multivariate analyses (all p < 0.05). The number of vascular risk factors and total number of FA symptoms were significantly associated in univariate analyses (p = 0.007) but not after adjusting for age (p = 0.055) or sex (p = 0.083). Conclusions: This study highlighted the potential importance of addictive-like behaviours in the secondary prevention of stroke. However, larger and longer-term studies investigating addictive-like eating in diverse samples of stroke patients are warranted to achieve precision medicine.
Kashin–Beck Disease: A Risk Factor for Sarcopenia and Its Interaction with Selenium
Authors: Wu Haotian , Chen Zhaoyu , Wang Ou , Jiang Tong , Huang Jian , Wang Jun , Lin Jianhao
Published: December 2024

Objectives: We aimed to explore the possible effects of Kashin–Beck disease (KBD) on the risk of sarcopenia and its possible interaction in the association between the risk of sarcopenia and element concentration. Methods: This cross-sectional study was conducted among individuals 18–75 years old in Qamdo, a KBD-endemic area. All individuals received physical and radiological examinations before recruitment. Patients with KBD were enrolled in the KBD group based on a diagnosis of national criteria WS/T 207-2010. Healthy individuals without KBD were enrolled in the non-KBD group. Participants with a history of element supplements, other severe musculoskeletal diseases, or organ dysfunctions were excluded. We adopted WOMAC scores for the assessment of musculoskeletal conditions and SARC-F scores for the risk of sarcopenia. Patients with SARC-F ≥ 4 were at risk of sarcopenia. Serum element concentrations were analyzed by inductively coupled plasma mass spectrometry. Dose–relationship effects of clinical scores and element concentrations on the risk of sarcopenia were determined in correlation analysis. Risk factors were identified using univariate and multivariate regression. Statistical analysis was conducted using R software. Results: A total of 65 patients with KBD and 38 participants without KBD were enrolled in the analysis. After propensity score matching, population characteristics were comparable in the two groups, and the incidence of SARC-F ≥ 4 was determined to be higher in the KBD group (p = 0.002). The WOMAC scores were correlated with SARC-F scores in the KBD group (p < 0.001) and non-KBD (p < 0.001) group, respectively. Further analysis proved that KBD was the independent risk factor for the risk of sarcopenia (p = 0.014). Moreover, high Selenium concentrations were associated with a low risk of sarcopenia in the non-KBD group (p = 0.047), while this association was not observed in the KBD group (p = 0.239). Conclusions: KBD as an independent risk factor increased the risk of sarcopenia for patients. Although high Se concentration was associated with a low risk of sarcopenia in participants without KBD, this association was not observed in those with KBD.
Retrospective Case-Control Study of Risk Factors for Carbapenem-Resistant Klebsiella pneumoniae Infection in Children in China
Authors: Wang Caizhen , Feng Lijie , Chen Ruomu , Chen Yuan
Published: December 2024

This study aims to investigate the risk factors for infection and mortality associated with carbapenem-resistant Klebsiella pneumoniae (CRKP) in hospitalized children, with the goal of providing valuable insights for the prevention and treatment of these bacterial infections. A retrospective case-control study was conducted, including 153 cases of carbapenem-sensitive K. pneumoniae infection in children and 49 cases of CRKP infection. Among the CRKP cases, 40 children survived and nine died. Logistic regression analysis was used to screen the risk factors for CRKP infection in children, establish a predictive model, and analyze the factors associated with mortality in CRKP-infected children. The results of the multivariate regression analysis showed that hematopoietic malignancies (OR = 28.272, 95% CI: 2.430–328.889), respiratory tract infections (OR = 0.173, 95% CI: 0.047–0.641), mechanical ventilation (OR = 3.002, 95% CI: 1.117–8.071), number of antibiotic agents (OR = 1.491, 95% CI: 1.177–1.889), WBC (OR = 0.849, 95% CI: 0.779–0.926), and neutrophil count (OR = 0.779, 95% CI: 0.677–0.896) were identified as significant factors associated with CRKP infection in children. Specifically, CRKP-infected children with a history of multiple hospitalizations within the past three months, blood stream infections, and decreased WBC and lymphocyte counts should be monitored closely due to poor prognosis. Underlying hematopoietic malignancies in children, non-respiratory tract infections, mechanical ventilation after admission, and use of multiple antibiotics without significant increase in white blood cell and neutrophil counts are major factors influencing CRKP infection. Particularly, CRKP-infected children with blood stream infections and no significant increase in neutrophil count should be closely monitored for potential severity of illness.
Skin Tear Treatment with Copaifera multijuga Hayne in Polymeric Hydrogel: A Randomized Clinical Trial
Authors: Cardinelli Camila Castanho , Passos Jéssica Teixeira Gâmba , Veiga-Junior Valdir Florêncio , de Oliveira Beatriz Guitton Renaud Baptista , Santos Elisabete Pereira dos , Neto Guilherme Guilhermino , Di Piero Karina Chamma , de Freitas Zaida Maria Faria
Published: December 2024

A double-blind, randomized, and controlled clinical trial with therapeutic intervention was performed at a university hospital in Rio de Janeiro to evaluate whether the addition of Copaifera multijuga Hayne oleoresin to a carboxypolymethylene hydrogel is more effective in skin tear healing than standard treatment. The sample consisted of 84 patients, predominantly men, with a mean age of 67.37 years. These participants were divided into three groups (29 in the intervention group, which received 10% Copaifera oleoresin; 28 in the intervention group, which received 2% Copaifera oleoresin; and 27 in the control group, which received carboxypolymethylene hydrogel). Data were tabulated and analyzed according to the relevant protocols and included only patients who had completed the treatment, while losses were excluded. Weekly follow-ups were conducted to monitor progress. The average healing time differed among the three groups (p > 0.05). There was also a significant difference in healing time between the two intervention groups. Ultimately, CopaibaPolyHy-2 led to significantly faster wound healing than CopaibaPolyHy-10 (p < 0.05). A high increase in granulation and epithelial tissue and a decrease in exudate quantity were observed in the CopaibaPolyHy-2 group. It was not possible to infer whether the wound size reduction differed between the treatments (p > 0.05). At the end of the study, 100% of wounds were healed, with 47,6% healing in week 2 (n = 40). No participants experienced local or serious adverse effects throughout the study period. The current study shows that CopaibaPolyHy-2 is effective, offering a statistically significantly faster healing time, better-quality tissue, and safe treatment for skin tears.
Ganoderma lucidum (Curtis) P. Karst. Immunomodulatory Protein Has the Potential to Improve the Prognosis of Breast Cancer Through the Regulation of Key Prognosis-Related Genes
Authors: Zuo Zanwen , Wen Ruihua , Jing Shuang , Chen Xianghui , Liu Ruisang , Xue Jianping , Zhang Lei , Li Qizhang
Published: December 2024

Background/Objectives: Breast cancer in women is the most commonly diagnosed and most malignant tumor. Although luminal A breast cancer (LumA) has a relatively better prognosis, it still has a persistent pattern of recurrence. Ganoderma lucidum (Curtis) P. Karst. is a kind of traditional Chinese medicine and has antitumor effects. In this study, we aimed to identify the genes relevant to prognosis, find novel targets, and investigate the function of the bioactive protein from G. lucidum, called FIP-glu, in improving prognosis. Methods: Gene expression data and clinical information of LumA breast cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Using bioinformatics methods, a predictive risk model was constructed to predict the prognosis for each patient. The cell counting kit-8 (CCK8) and clone formation assays were used to validate gene function. The ability of FIP-glu to regulate RNA levels of risk genes was validated. Results: Six risk genes (slit-roundabout GTPase-activating protein 2 (SRGAP2), solute carrier family 35 member 2 (SLC35A2), sequence similarity 114 member A1 (FAM114A1), tumor protein P53-inducible protein 11 (TP53I11), transmembrane protein 63C (TMEM63C), and polymeric immunoglobulin receptor (PIGR)) were identified, and a prognostic model was constructed. The prognosis was worse in the high-risk group and better in the low-risk group. The receiver operating characteristic (ROC) curve confirmed the model’s accuracy. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the differentially expressed genes (DEGs) between the high- and low-risk groups were significantly enriched in the immune responses. TMEM63C could promote tumor viability, growth, and proliferation in vitro. FIP-glu significantly regulated these risk genes, and attenuated the promoting effect of TMEM63C in breast cancer cells. Conclusions: SRGAP2, SLC35A2, FAM114A1, TP53I11, TMEM63C, and PIGR were identified as the potential risk genes for predicting the prognosis of patients. TMEM63C could be a potential novel therapeutic target. Moreover, FIP-glu was a promising drug for improving the prognosis of LumA breast cancer.
Evaluation of the Drug–Drug Interaction Potential of Cannabidiol Against UGT2B7-Mediated Morphine Metabolism Using Physiologically Based Pharmacokinetic Modeling
Authors: Coates Shelby , Bardhi Keti , Prasad Bhagwat , Lazarus Philip
Published: December 2024

Background: Morphine is a commonly prescribed opioid analgesic used to treat chronic pain. Morphine undergoes glucuronidation by UDP-glucuronosyltransferase (UGT) 2B7 to form morphine-3-glucuronide and morphine-6-glucuronide. Morphine is the gold standard for chronic pain management and has a narrow therapeutic index. Reports have shown that chronic pain patients have increasingly used other supplements to treat their chronic pain, including cannabidiol (CBD). Up to 50% of chronic pain patients report that they co-use cannabis with their prescribed opioid for pain management, including morphine. Previous work has shown that cannabidiol is a potent inhibitor of UGT2B7, including morphine-mediated metabolism. Co-use of morphine and CBD may result in unwanted drug–drug interactions (DDIs). Methods: Using available physiochemical and clinical parameters, morphine and CBD physiologically based pharmacokinetic (PBPK) models were developed and validated in both healthy and cirrhotic populations. Models for the two populations were then combined to predict the severity and clinical relevance of the potential DDIs during coadministration of both morphine and CBD in both healthy and hepatic-impaired virtual populations. Results: The predictive DDI model suggests that a ~5% increase in morphine exposure is to be expected in healthy populations. A similar increase in exposure of morphine is predicted in severe hepatic-impaired populations with an increase of ~10. Conclusions: While these predicted increases in morphine exposure are below the Food and Drug Administration’s cutoff (1.25-fold increase), morphine has a narrow therapeutic index and a 5–10% increase in exposure may be clinically relevant. Future clinical studies are needed to fully characterize the clinical relevance of morphine-related DDIs.
How to Fabricate Hyaluronic Acid for Ocular Drug Delivery
Authors: Kim Martha , Jung Mi-Young , Lee Do-Yeon , Ahn So Min , Lee Gyeong Min , Park Choul Yong
Published: December 2024

This review aims to examine existing research on the development of ocular drug delivery devices utilizing hyaluronic acid (HA). Renowned for its exceptional biocompatibility, viscoelastic properties, and ability to enhance drug bioavailability, HA is a naturally occurring biopolymer. The review discussed specific mechanisms by which HA enhances drug delivery, including prolonging drug residence time on ocular surfaces, facilitating controlled drug release, and improving drug penetration through ocular tissues. By focusing on these unique functionalities, this review highlights the potential of HA-based systems to revolutionize ocular treatment. Various fabrication techniques for HA-based ocular drug delivery systems, including hydrogels, nanoparticles, and microneedles, are discussed, highlighting their respective advantages and limitations. Additionally, this review explores the clinical applications of HA-based devices in treating a range of ocular diseases, such as dry eye syndrome, glaucoma, retinal disorders, and ocular infections. By comparing the efficacy and safety profiles of these devices with traditional ocular drug delivery methods, this review aims to provide a comprehensive understanding of the potential benefits and challenges associated with HA-based systems. Moreover, this review discusses current limitations and future directions in the field, such as the need for standardized fabrication protocols, long-term biocompatibility studies, and large-scale clinical trials. The insights and advancements presented in this review aim to guide future research and development efforts, ultimately enhancing the effectiveness of ocular drug delivery and improving patient outcomes.
Mining of Candidate Genes and Developing Molecular Markers Associated with Pokkah Boeng Resistance in Sugarcane (Saccharum spp.)
Authors: Lin Haidong , Jiang Zhengjie , He Tuan , Li Guomeng , Zhao Mengyu , Su Liangyinan , Zhao Jihan , Zou Chengwu , Yang Xiping
Published: December 2024

Sugarcane Pokkah Boeng (PB), a fungal disease caused by Fusarium spp., poses a significant threat to sugar industries globally. Breeding sugarcane varieties resistant to PB has become a priority, and the mining of PB resistance genes and the development of molecular markers provide a solid foundation for this purpose. This work comprehensively analyzes the genetic components of sugarcane’s resistance to PB using transcriptome sequencing. A segregating population was created by crossing the susceptible parent ROC25 with the resistant parent Yunzhe89-7, which is a traditional cultivar known for its PB resistance. Transcriptome analysis uncovered many differentially expressed genes (DEGs) associated with PB resistance. Utilizing weighted gene co-expression network analysis (WGCNA), we identified gene modules closely related to disease phenotypes. We annotated their functions with bioinformatics tools, particularly focusing on genes enriched in the plant immune response’s MAPK signaling pathway and ABC transporter synthesis pathways. In addition, by integrating whole-genome resequencing data of parental lines and transcriptome data of progeny, we identified a series of putative molecular markers that potentially effectively differentiate between highly resistant and susceptible materials. Our study provides crucial genetic resources and molecular methodologies that are essential for the advancement of sugarcane varieties with improved resistance to PB. These innovations are expected to accelerate the breeding process greatly.
Growth Allocation Shifts in the Invasive Hydrilla verticillata Under Interspecific Competition with Native Submerged Macrophytes
Authors: da Costa Letícia , Vieira Luíz Alberto , Michelan Thaísa Sala , Vale Alvaro Herrera , Chiba de Castro Wagner Antonio
Published: December 2024

Communities with high native species diversity tend to be less susceptible to the establishment of invasive species, especially in studies that test their local impact. This study investigated the impact of competition between native submerged aquatic macrophytes (SAMs) (Egeria najas and Egeria densa) and the exotic Hydrilla verticillata, recognized for its invasive potential in aquatic ecosystems, through a mesocosm experiment conducted over six months. Two treatments were evaluated: the intraspecific competition of H. verticillata and an interspecific competition involving all three species. The plants were cultivated under controlled conditions, with the foliar and subterranean biomass being monitored to analyze resource allocation patterns. The results showed that, under interspecific competition, the mean foliar biomass of H. verticillata was significantly higher compared to the intraspecific treatment, while the subterranean biomass was reduced in the presence of native species. We conclude that native species alter the biomass allocation pattern of the invader, favoring foliar structures over subterranean ones. Among the mechanisms of invasiveness, differential resource allocation represents an important strategy for the adaptation and competitiveness of invasive species influenced by environmental factors and resource competition. These findings contribute to the understanding of competitive interactions in aquatic ecosystems and have implications for the management and control of invasive species, highlighting the importance of promoting native diversity to mitigate invasibility. Future studies should investigate the impacts of reduced subterranean structures on the persistence and spread of submerged invasive species.
Small Gap Dynamics in High Mountain Central European Spruce Forests—The Role of Standing Dead Trees in Gap Formation
Authors: Sedmáková Denisa , Jaloviar Peter , Mišíková Oľga , Šumichrast Ladislav , Slováčková Barbora , Kucbel Stanislav , Vencurik Jaroslav , Bosela Michal , Sedmák Róbert
Published: December 2024

Gap dynamics are driving many important processes in the development of temperate forest ecosystems. What remains largely unknown is how often the regeneration processes initialized by endogenous mortality of dominant and co-dominant canopy trees take place. We conducted a study in the high mountain forests of the Central Western Carpathians, naturally dominated by the Norway spruce. Based on the repeated forest inventories in two localities, we quantified the structure and amount of deadwood, as well as the associated mortality of standing dead canopy trees. We determined the basic specific gravity of wood and anatomical changes in the initial phase of wood decomposition. The approach for estimating the rate of gap formation and the number of canopy trees per unit area needed for intentional gap formation was formulated based on residence time analysis of three localities. The initial phase of gap formation (standing dead tree in the first decay class) had a narrow range of residence values, with a 90–95% probability that gap age was less than 10 or 13 years. Correspondingly, a relatively constant absolute number of 12 and 13 canopy spruce trees per hectare died standing in 10 years, with a mean diameter reaching 50–58 cm. Maximum diameters trees (70–80 cm) were represented by 1–4 stems per hectare. The values of the wood-specific gravity of standing trees were around 0.370–0.380 g.cm−3, and varied from 0.302 to 0.523 g.cm−3. Microscopically, our results point out that gap formation is a continuous long-lasting process, starting while canopy trees are living. We observed early signs of wood degradation and bacteria, possibly associated with bark beetles, that induce a strong effect when attacking living trees with vigorous defenses. New information about the initial phase of gap formation has provided a basis for the objective proposal of intervals and intensities of interventions, designed to promote a diversified structure and the long-term ecological stability of the mountain spruce stands in changing climate conditions.
Genome-Wide Identification of Xyloglucan Endotransglucosylase/Hydrolase Multigene Family in Chinese Jujube (Ziziphus jujuba) and Their Expression Patterns Under Different Environmental Stresses
Authors: Refaiy Mohamed , Tahir Muhammad , Jiao Lijun , Zhang Xiuli , Zhang Huicheng , Chen Yuhan , Xu Yaru , Song Shuang , Pang Xiaoming
Published: December 2024

The Xyloglucan endotransglucosylase/hydrolase (XTH) family, a group of cell wall-modifying enzymes, plays crucial roles in plant growth, development, and stress adaptation. The quality and yield of Chinese jujube (Ziziphus jujuba) fruit are significantly impacted by environmental stresses, including excessive salinity, drought, freezing, and disease. However, there has been no report of the XTH encoding genes present in the Chinese jujube genome and their response transcription level under various stresses. This study provides an in-depth analysis of ZjXTH genes in the genome of Chinese jujube and elucidates their structural motifs, regulatory networks, and expression patterns under various stresses. A total of 29 ZjXTH genes were identified from the Ziziphus jujuba genome. Phylogenetic analysis classifies ZjXTH genes into four distinct groups, while conserved motifs and domain analyses reveal coordinated xyloglucan modifications, highlighting key shared motifs and domains. Interaction network predictions suggest that ZjXTHs may interact with proteins such as Expansin-B1 (EXPB1) and Pectin Methylesterase 22 (PME22). Additionally, cis-regulatory element analysis enhances our understanding of Chinese jujube plant’s defensive systems, where TCA- and TGACG-motifs process environmental cues and orchestrate stress responses. Expression profiling revealed that ZjXTH1 and ZjXTH5 were significantly upregulated under salt, drought, freezing, and phytoplasma infection, indicating their involvement in biotic and abiotic stress responses. Collectively, these findings deepen our understanding of the functional roles of Chinese jujube XTHs, emphasizing their regulatory function in adaptive responses in Chinese jujube plants.
Response of Arabidopsis thaliana to Flooding with Physical Flow
Authors: Kaji Momoko , Katano Kazuma , Anee Taufika Islam , Nitta Hiroshi , Yamaji Ryotaro , Shimizu Rio , Shigaki Shunsuke , Suzuki Hiroyuki , Suzuki Nobuhiro
Published: December 2024

Flooding causes severe yield losses worldwide, making it urgent to enhance crop tolerance to this stress. Since natural flooding often involves physical flow, we hypothesized that the effects of submergence on plants could change when combined with physical flow. In this study, we analyzed the growth and transcriptome of Arabidopsis thaliana exposed to submergence or flooding with physical flow. Plants exposed to flooding with physical flow had smaller rosette diameters, especially at faster flow rates. Transcriptome analysis revealed that “defense response” transcripts were highly up-regulated in response to flooding with physical flow. In addition, up-regulation of transcripts encoding ROS-producing enzymes, SA synthesis, JA synthesis, and ethylene signaling was more pronounced under flooding with physical flow when compared to submergence. Although H2O2 accumulation changed in response to submergence or flooding with physical flow, it did not lead to lipid peroxidation, suggesting a role for ROS as signaling molecules under these conditions. Multiple regression analysis indicated possible links between rosette diameter under flooding with physical flow and the expression of Rbohs and SA synthesis transcripts. These findings suggest that pathogen defense responses, regulated by SA and ROS signaling, play crucial roles in plant responses to flooding with physical flow.
Pollen Morphological Characteristics of 46 Germplasm Resources of Polygonatum and Its Taxonomic Implications
Authors: Ding Mingyue , Xie Qian , Jiang Lai , Liu Lingling , Luo Wenbao , Su Hailan , Chen Qingxi
Published: December 2024

To elucidate the morphological diversity and genetic characteristics of the pollen of Polygonatum species, this study utilized a total of 46 samples encompassing six species and one variety of Polygonatum. Scanning electron microscopy (SEM) was employed to examine the morphological traits of the pollen and to analyze the evolutionary patterns and genetic relationships among Polygonatum species. The results indicate that the pollen grains of the 46 Polygonatum germplasm are uniformly characterized as monads, heteropolar, bilaterally symmetrical, atreme, and possess a mono-sulcus. They were peroblate (P/E-ratio = 0.36–0.42) in shape and medium to large (P = 18.17–27.15 μm, E = 44.11–67.07 μm) in size. And there are four types of exine ornamentation: reticulate, reticulate–perforate, reticulate–rugulate, and reticulate–verrucate. The 46 germplasm resources were classified into four clusters based on the results of a pollen morphology clustering analysis: P. cyrtonema and P. macropodum were grouped into cluster I, P. filipes and P. odoratum into cluster II, P. kingianum and P. kingianum var. grandifolium into cluster III, and P. alternicirrhosum was classified as cluster IV, standing alone. This study tentatively suggests that pollen morphology, particularly pollen size and exine ornamentation, can serve as a valuable reference for the classification, genetic relationship, and evolutionary patterns of the genus Polygonatum.
Studying the Antifungal Effects of Ageratina adenophora (Sprengel) R. King and H. Robinson (=Eupatorium adenophorum Sprengel) as a Bio-Fumigant Plant Alone and in Combination with Biochar Against Pythium aphanidermatum (Edson) Fitz
Authors: Parsiaaref Shiva , Cao Aocheng , Li Yuan , Ebadollahi Asgar , Parmoon Ghasem , Gholamnezhad Jalal , Wang Qiuxia , Yan Dongdong , Fang Wensheng , Song Zhaoxin , Wang Xianli , Zhang Min
Published: December 2024

Pythium spp. are soil-borne pathogens that cause damping-off and root rot diseases in many plant species such as cucumber. In the current study, the effect of dried roots–stems and leaves of Ageratina adenophora (Sprengel) R. King and H. Robinson (=Eupatorium adenophorum Sprengel) alone and in combination with pyrogenic biomass biochar to control Pythium aphanidermatum (Edson) Fitz was assessed. In four treatments of leaves, roots–stems, leaves + biochar, and roots–stems + biochar, it was observed that the treatment with leaves at an Emax (maximal effective concentration on control fungi) of 79 g/kg of soil had the most antifungal effect on P. aphanidermatum. Also, the Cmax (the highest level of control) increased with time and reached 82.4% and 71% on days 30 and 60, respectively. The highest cucumber fresh fruit weight and the highest height of the stems in the greenhouse were observed in leaf treatment of A. adenophora. Biochar did not have any remarkable controlling effect on P. aphanidermatum, and its population increased. The main compounds extracted from the dried leaves and roots–stems of A. adenophora, including α-pinene, nonanone, hexahydronaphthalene, 3-undecanone, muurolene, and heneicosane, had antifungal properties. We concluded that the leaves of A. adenophora have the potential to be used as a bio-fumigant for P. aphanidermatum management.
Changes in Endogenous Carotenoids, Flavonoids, and Phenolics of Drought-Stressed Broccoli Seedlings After Ascorbic Acid Preconditioning
Authors: Cai Linqi , Abbey Lord , MacDonald Mason
Published: December 2024

Drought is an abiotic disturbance that reduces photosynthesis, plant growth, and crop yield. Ascorbic acid (AsA) was utilized as a seed preconditioning agent to assist broccoli (Brassica oleracea var. italica) in resisting drought. However, the precise mechanism by which AsA improves seedlings’ development remains unknown. One hypothesis is that AsA works via antioxidant mechanisms and reduces oxidative stress. This study aims to confirm the effect of varied concentrations of AsA (control, 0 ppm, 1 ppm, or 10 ppm) on seedling growth and changes in the antioxidant status of broccoli seedlings under regular watering or drought stress. AsA increased shoot dry mass, leaf area, net photosynthesis, and water use efficiency in watered and drought-stressed seedlings. AsA significantly (p < 0.001) increased carotenoid content in watered and drought-stressed seedlings by approximately 27% and 111%, respectively. Drought increased chlorophyll b, flavonoids, phenolics, ascorbate, and hydrogen peroxide production in control seedlings, but either had no effect or less effect on plants preconditioned with 10 ppm AsA. There was no improvement in reactive oxygen species scavenging in AsA-preconditioned seedlings compared to the control. The absence or reduction in biochemical indicators of stress suggests that preconditioned broccoli seedlings do not perceive stress the same as control seedlings. In conclusion, the consistent increase in carotenoid concentration suggests that carotenoids play some role in the preconditioning response, though the exact mechanism remains unknown.
Foliar Nutrition Strategies for Enhancing Phenolic and Amino Acid Content in Olive Leaves
Authors: Polić Pasković Marija , Herak Ćustić Mirjana , Lukić Igor , Marcelić Šime , Žurga Paula , Vidović Nikolina , Major Nikola , Goreta Ban Smiljana , Pecina Marija , Ražov Josip , Likar Matevž , Pongrac Paula , Pasković Igor
Published: December 2024

Studies on selenium (Se) and silicon (Si) foliar biostimulation of different plants have been shown to affect concentrations of phenolic compounds. However, their effects on olive (Olea europaea L.) primary and secondary metabolites have not been fully investigated. Therefore, the effects of foliar sprayed Si and Se and their combination on the concentration of phenols, selected metabolites involved in the phenol biosynthesis, and mineral elements concentrations were determined in olive leaves of the field-grown cultivar Leccino. During the summer period, leaves were foliar sprayed three times, after which were sampled 30 days after the corresponding application. In general, foliar treatment of Si or Se increased the concentrations of several predominant phenolic compounds, such as oleuropein, oleacein, and specific flavonoids. The effects were especially pronounced after the third application in the harvest time sampling time. Amino acids and other phenol precursors were also significantly affected. The effects were phenol-specific and depended on the treatment, sampling time, and treatment × sampling time interaction. The response of verbascoside to the applied treatments appeared to be closely linked to corresponding changes in its amino acid precursors, such as tyrosine, while its connection with tryptophan and IAA has to be cautiously considered. In contrast, for other phenolic compounds like secoiridoids, a clear interdependence with their precursors was not identified, likely due to the more complex nature of their biosynthesis. The effects on the concentrations of elements other than Se and Si were milder.