bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure Identification of Ganoderma lucidum Spore Polysaccharides and Their Antitumor Activity In Vivo
Authors: Liu Hui-Min , Cheng Jun , Wang Xiao-Yi , Jiang Yan , Ni Jia , Zhang Yun , Wang Wei
Published: May 2024

Ganoderma lucidum spore powder, valued for its nutritional and medicinal properties, contains polysaccharides crucial for its efficacy. However, the complex structural nature of these polysaccharides necessitates further investigation to fully realize their potential. This study aimed to investigate the effects of acid heat treatment on Ganoderma lucidum spore polysaccharides (GLSPs) to enhance their properties and application in antitumor activity. The GLSP was obtained via acid heat treatment, concentration, and centrifugal separation. This process led to a notable reduction in polysaccharide molecular weight, increasing water solubility and bioavailability. Analytical techniques including NMR spectroscopy and methylation analysis revealed a polysaccharide composition comprising four distinct monosaccharides, with molecular weights of 3291 Da (Mw) and 3216 Da (Mn). Six different linkage modes were identified, with a molar ratio of 1:5:2:3:4:3. In vivo experiments demonstrated the GLSP’s significant inhibitory effect on the growth of four tumor models (sarcoma S180, Lewis lung cancer, liver cancer H22, and colon cancer C26) in mice, with no observed toxicity. These findings suggest the GLSP’s potential as an antitumor therapeutic agent for clinical use.
Recent Advances in Metal-Catalyzed Approaches for the Synthesis of Quinazoline Derivatives
Authors: Nandwana Nitesh K. , Patel Om P. S. , Mehra Manish K. , Kumar Anil , Salvino Joseph M.
Published: May 2024

Quinazolines are an important class of heterocyclic compounds that have proven their significance, especially in the field of organic synthesis and medicinal chemistry because of their wide range of biological and pharmacological properties. Thus, numerous synthetic methods have been developed for the synthesis of quinazolines and their derivatives. This review article briefly outlines the new synthetic methods for compounds containing the quinazoline scaffold employing transition metal-catalyzed reactions.
Pre-Steady-State and Steady-State Kinetic Analysis of Butyrylcholinesterase-Catalyzed Hydrolysis of Mirabegron, an Arylacylamide Drug
Authors: Shaihutdinova Zukhra , Masson Patrick
Published: May 2024

The β-adrenergic drug Mirabegron, a drug initially used for the treatment of an overactive bladder, has new potential indications and is hydrolyzed by butyrylcholinesterase (BChE). This compound is one of the only arylacylamide substrates to be catabolized by BChE. A steady-state kinetic analysis at 25 °C and pH 7.0 showed that the enzyme behavior is Michaelian with this substrate and displays a long pre-steady-state phase characterized by a burst. The induction time, τ, increased with substrate concentration (τ ≈ 18 min at maximum velocity). The kinetic behavior was interpreted in terms of hysteretic behavior, resulting from a slow equilibrium between two enzyme active forms, E and E′. The pre-steady-state phase with the highest activity corresponds to action of the E form, and the steady state corresponds to action of the E′ form. The catalytic parameters were determined as kcat = 7.3 min−1 and Km = 23.5 μM for the initial (burst) form E, and kcat = 1.6 min−1 and Km = 3.9 μM for the final form E′. Thus, the higher affinity of E′ for Mirabegron triggers the slow enzyme state equilibrium toward a slow steady state. Despite the complexity of the reaction mechanism of Mirabegron with BChE, slow BChE-catalyzed degradation of Mirabegron in blood should have no impact on the pharmacological activities of this drug.
Syrian Hamsters Model Does Not Reflect Human-like Disease after Aerosol Exposure to Encephalitic Alphaviruses
Authors: Gardner Christina L. , Erwin-Cohen Rebecca A. , Lewis Bridget S. , Bakken Russell R. , Honnold Shelley P. , Glass Pamela J. , Burke Crystal W.
Published: May 2024

Venezuelan (VEE), eastern (EEE), and western (WEE) equine encephalitis viruses are encephalitic New World alphaviruses that cause periodic epizootic and epidemic outbreaks in horses and humans that may cause severe morbidity and mortality. Currently there are no FDA-licensed vaccines or effective antiviral therapies. Each year, there are a limited number of human cases of encephalitic alphaviruses; thus, licensure of a vaccine or therapeutic would require approval under the FDA animal rule. Approval under the FDA animal rule requires the disease observed in the animal model to recapitulate what is observed in humans. Currently, initial testing of vaccines and therapeutics is performed in the mouse model. Unfortunately, alphavirus disease manifestations in a mouse do not faithfully recapitulate human disease; the VEEV mouse model is lethal whereas in humans VEEV is rarely lethal. In an effort to identify a more appropriate small animal model, we evaluated hamsters in an aerosol exposure model of encephalitic alphavirus infection. The pathology, lethality, and viremia observed in the infected hamsters was inconsistent with what is observed in NHP models and humans. These data suggest that hamsters are not an appropriate model for encephalitic alphaviruses to test vaccines or potential antiviral therapies.
Solvothermally Grown Oriented WO3 Nanoflakes for the Photocatalytic Degradation of Pharmaceuticals in a Flow Reactor
Authors: Cescon Mirco , Stevanin Claudia , Ardit Matteo , Orlandi Michele , Martucci Annalisa , Chenet Tatiana , Pasti Luisa , Caramori Stefano , Cristino Vito
Published: May 2024

Contamination by pharmaceuticals adversely affects the quality of natural water, causing environmental and health concerns. In this study, target drugs (oxazepam, OZ, 17-α-ethinylestradiol, EE2, and drospirenone, DRO), which have been extensively detected in the effluents of WWTPs over the past decades, were selected. We report here a new photoactive system, operating under visible light, capable of degrading EE2, OZ and DRO in water. The photocatalytic system comprised glass spheres coated with nanostructured, solvothermally treated WO3 that improves the ease of handling of the photocatalyst and allows for the implementation of a continuous flow process. The photocatalytic system based on solvothermal WO3 shows much better results in terms of photocurrent generation and photocatalyst stability with respect to state-of-the-art WO3 nanoparticles. Results herein obtained demonstrate that the proposed flow system is a promising prototype for enhanced contaminant degradation exploiting advanced oxidation processes.
Involvement of GPR43 Receptor in Effect of Lacticaseibacillus rhamnosus on Murine Steroid Resistant Chronic Obstructive Pulmonary Disease: Relevance to Pro-Inflammatory Mediators and Oxidative Stress in Human Macrophages
Authors: Sá Ana Karolina , Olímpio Fabiana , Vasconcelos Jessica , Rosa Paloma , Faria Neto Hugo Caire , Rocha Carlos , Camacho Maurício Frota , Barcick Uilla , Zelanis Andre , Aimbire Flavio
Published: May 2024

Background: Cytokine storm and oxidative stress are present in chronic obstructive pulmonary disease (COPD). Individuals with COPD present high levels of NF-κB-associated cytokines and pro-oxidant agents as well as low levels of Nrf2-associated antioxidants. This condition creates a steroid-resistant inflammatory microenvironment. Lacticaseibacillus rhamnosus (Lr) is a known anti-cytokine in lung diseases; however, the effect of Lr on lung inflammation and oxidative stress in steroid-resistant COPD mice remains unknown. Objective: Thus, we investigated the Lr effect on lung inflammation and oxidative stress in mice and macrophages exposed to cigarette smoke extract (CSE) and unresponsive to steroids. Methods: Mice and macrophages received dexamethasone or GLPG-094 (a GPR43 inhibitor), and only the macrophages received butyrate (but), all treatments being given before CSE. Lung inflammation was evaluated from the leukocyte population, airway remodeling, cytokines, and NF-κB. Oxidative stress disturbance was measured from ROS, 8-isoprostane, NADPH oxidase, TBARS, SOD, catalase, HO-1, and Nrf2. Results: Lr attenuated cellularity, mucus, collagen, cytokines, ROS, 8-isoprostane, NADPH oxidase, and TBARS. Otherwise, SOD, catalase, HO-1, and Nrf2 were upregulated in Lr-treated COPD mice. Anti-cytokine and antioxidant effects of butyrate also occurred in CSE-exposed macrophages. GLPG-094 rendered Lr and butyrate less effective. Conclusions: Lr attenuates lung inflammation and oxidative stress in COPD mice, suggesting the presence of a GPR43 receptor-dependent mechanism also found in macrophages.
Comparing the Efficacy of Digital and In-Person Weight Loss Interventions for Patients with Obesity and Glycemic Disorders: Evidence from a Randomized Non-Inferiority Trial
Authors: Moravcová Katarína , Sovová Markéta , Ožana Jaromír , Karbanová Martina , Klásek Jan , Kolasińska Agnieszka Barbara , Sovová Eliška
Published: May 2024

Digital weight loss interventions present a viable and cost-effective alternative to traditional therapy. However, further evidence is needed to establish the equal effectiveness of both approaches. This randomized controlled non-inferiority trial aimed to compare the effects of an intensive in-person weight loss intervention program with Vitadio digital therapy. One hundred patients with obesity and diagnosed with type 2 diabetes, prediabetes, or insulin resistance were enrolled and randomly assigned to one of the two treatment groups. Over a 6-month period, the control group received five in-person consultations with a physician who specialized in obesity treatment, a dietitian and/or a nutrition nurse, while the intervention group followed the digital program based on a multimodal therapeutic approach. The extent of weight loss was assessed and compared between the groups. Additionally, changes in body composition and metabolic parameters for the digital intervention group were analyzed. The study results demonstrated comparable effectiveness of both treatments for weight reduction. The positive effects of Vitadio were further evidenced by favorable changes in body composition and lipid metabolism and improved glycemic control in the intervention group. These findings suggest that Vitadio is an effective tool for assisting patients with managing obesity and preventing diabetes progression.
Development and Validation of the Serious Educational Game in Nursing Appraisal Scale
Authors: Fernandes Carla Sílvia , Campos Maria Joana , Moreira Maria Teresa , Lima Andreia , Ferreira Salomé , Martins Maria Manuela
Published: May 2024

Objectives: This study aims to develop and validate the Serious Educational Game in Nursing Appraisal Scale (SEGiNAS), a tool designed to evaluate the implementation of serious games within nurse education contexts of quantity of process, quality of process, and learning outcomes. Methods and Materials: This methodological and psychometric study aimed to develop and validate a scale. The item generation phase was based on the cognitive theory of multimedia learning, resulting in a 20-item scale. The validation phase involved evaluating the psychometric scale by surveying 160 Portuguese nurses. Results: A factor analysis revealed a three-factor structure corresponding to the scale’s designed dimensions, explaining a total variance of 64.5%. The scale demonstrated high internal consistency for all factors, including engagement and teaching effectiveness (0.925), learning impact and practical application (0.883), and content relevance and clarity (0.848). The dimensions were engagement and teaching effectiveness, learning impact and practical application, and content relevance and clarity. Conclusions: The SEGiNAS scale represents a valid and reliable tool for evaluating serious games in nursing education. Its development fills an existing gap in assessing the teaching–learning process with serious games. This study was not registered.
Identifying Barriers to the Acquisition of Knowledge about Skin Integrity Impairment in Nursing Students: An Educational Intervention
Authors: Sánchez-Gálvez Javier , Martínez-Isasi Santiago , Sánchez-Hernández Miriam , Vegue-Parra Eva , Yacobis-Cervantes Tamara Rafaela , Mateo-Ramírez Francisco , Fernández-García Daniel
Published: May 2024

Background: Wound healing competence is implied in the nursing profession, but there is no standardized content regulation for wound care in university curricula. The primary objective of this study was to identify the barriers to the acquisition of knowledge about skin integrity impairment. Methods: A quasi-experimental pre-test and post-test study with an ad hoc questionnaire involved 304 students (control: 165; intervention: 139) from June to July 2023. A 10-h educational intervention focused on skin integrity assessment and treatment was conducted. Results: The control group, scoring 17 ± 0.22 out of a maximum of 61, achieved a significantly lower final test score (p < 0.001) compared to the wound care educational intervention group, with the pre-test group scoring 30 ± 0.76 and the post-test group scoring 43 ± 0.61. The educational intervention in wound care program improved nursing students’ knowledge of prevention, assessment/diagnosis, treatment, lower limb wounds, and wound bed preparation by replacing the number of "Don’t know" answers in the post-test group with correct answers. Conclusions: The barriers identified to the acquisition of knowledge about skin integrity impairment in nursing studies are the following: the transversality of teaching, the teaching and evaluation system, and the variability in the training of professionals and teachers in charge of their education. The educational intervention can be used to consolidate knowledge and to enhance students’ self-confidence in caring for patients with wounds.
Effectiveness of “Escape Room” Educational Technology in Nurses’ Education: A Systematic Review
Authors: González-de la Torre Héctor , Hernández-De Luis María-Naira , Mies-Padilla Sergio , Camacho-Bejarano Rafaela , Verdú-Soriano José , Rodríguez-Suárez Claudio-Alberto
Published: May 2024

Escape room games are educational gamification technologies that consist of introducing a team of players into a physical or digital space in search of clues to answer puzzles, riddles or enigmas and solve a mystery or problem. This study aims to determine the effectiveness of escape room games on the training of nursing students in an international context. A systematic review was carried out in MEDLINE, WOS, SCOPUS, CINAHL and LILACS databases using the MeSH terms “Education, Nursing” and “Educational Technology”, and the free term “Escape room”, combined with Boolean operators AND/OR. Intervention studies in Spanish, English and Portuguese were included, without limitation for the year of publication. Selection and critical appraisal were conducted by two independent reviewers. A total of n = 13 interventional studies were included (n = 2 Randomized Clinical Trials and n = 11 quasi-experimental design). Escape rooms are a recent and growing educational methodology, increasingly used in academia and in the training of nurses and nursing students. However, it is necessary to expand their use and the quality of the studies in a greater number of contexts. Furthermore, it is necessary to homogenize and standardize validated instruments to evaluate the effectiveness of escape rooms in the nursing education area.
Parents’ Participation in Care during Neonatal Intensive Care Unit Stay in COVID-19 Era: An Observational Study
Authors: Buccione Emanuele , Scarponcini Fornaro Davide , Pieragostino Damiana , Natale Luca , D’Errico Adelaide , Chiavaroli Valentina , Rasero Laura , Bambi Stefano , Della Pelle Carlo , Di Valerio Susanna
Published: May 2024

Background: Parents play a crucial role in the care of infants during their stay in the neonatal intensive care unit (NICU). Recent studies have reported a decrease in parental participation due to the coronavirus disease (COVID-19) pandemic, which has led to restricted access policies in hospitals. The aim of this study was to describe the barriers to good parental participation during their stay in the neonatal intensive care unit in the COVID-19 era. Methods: This was a quantitative, observational study. Results: A total of 270 parents participated in this study. Mothers’ participation in care was higher than that of fathers (p = 0.017). Parents who lived at the birth of their first child reported a better level of participation in care compared to those who lived at the birth of their second-born (p = 0.005). Parents of extremely preterm neonates reported a lower interaction with their infants than parents of term newborns (p < 0.001). Conclusions: Some disadvantaged categories reported lower scores for cultural and linguistic minorities, parents of multiple children, and fathers. The COVID-19 pandemic has made several family-centred care activities impossible, with a higher impact on those who benefited most of these facilities. This study was prospectively approved by the IRB-CRRM of the University “G. d’Annunzio” Chieti-Pescara on 23 January 2024 (approval number CRRM: 2023_12_07_01).
Understanding the Impact of the Nurse Manager’s Vocation for Leadership on the Healthcare Workplace Environments in Mexico: A Grounded Theory Approach
Authors: Yañez-Lozano Angeles , Lillo-Crespo Manuel
Published: May 2024

Background: Leadership in any managerial position that a nurse may hold appears to be closely connected to fostering positive and productive work environments within healthcare settings. However, not all nurse managers are characterized by leadership, and not all nurse leaders are nurse managers. In countries, such as Mexico, those who occupy these roles have barely sufficient training in management, are mainly characterized by their experience in one clinical specialty and their vocation for leadership is not a requirement. Our study aims to understand how the leadership vocation that some nurse managers have in their daily practice could impact the work environments of healthcare organizations in Mexico. Methods: A qualitative design was carried out through a grounded theory approach based on Corbin & Strauss, interviewing individually 13 nurse managers with representative experience in Mexican public sector hospitals. Results: According to the interviewees, the meaning of vocation is based mainly on the love for their profession, on the vocation of being a nurse and caring for people, as well as on the development of their own natural leadership potential for decision-making in practice. This situation produces positive feedback on themselves by generating productive effects in the work environment, consequently strengthening them to better organize professional resources and therefore producing improvements. Conclusions: The nurse manager’s vocation of leadership derives from both the vocation of being a practicing nurse and the vocation for being a leader, positively impacting and productively contributing to the improvement of the work environment. Consequently, nurse managers with vocation for leadership should be the gold standard role in any healthcare organization. This study was retrospectively registered with the (registros-OSF-bmyvz-v1) on the (26 July 2023) registration number (10.17605/OSF.IO/BMYVZ).
Label-Free Detection of African Swine Fever and Classical Swine Fever in the Point-of-Care Setting Using Photonic Integrated Circuits Integrated in a Microfluidic Device
Authors: Manessis Georgios , Frant Maciej , Podgórska Katarzyna , Gal-Cisoń Anna , Łyjak Magdalena , Urbaniak Kinga , Woźniakowski Grzegorz , Denes Lilla , Balka Gyula , Nannucci Lapo , Griol Amadeu , Peransi Sergio , Basdagianni Zoitsa , Mourouzis Christos , Giusti Alessandro , Bossis Ioannis
Published: May 2024

Swine viral diseases have the capacity to cause significant losses and affect the sector’s sustainability, a situation further exacerbated by the lack of antiviral drugs and the limited availability of effective vaccines. In this context, a novel point-of-care (POC) diagnostic device incorporating photonic integrated circuits (PICs), microfluidics and information, and communication technology into a single platform was developed for the field diagnosis of African swine fever (ASF) and classical swine fever (CSF). The device targets viral particles and has been validated using oral fluid and serum samples. Sensitivity, specificity, accuracy, precision, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated to assess the performance of the device, and PCR was the reference method employed. Its sensitivities were 80.97% and 79%, specificities were 88.46% and 79.07%, and DOR values were 32.25 and 14.21 for ASF and CSF, respectively. The proposed POC device and PIC sensors can be employed for the pen-side detection of ASF and CSF, thus introducing novel technological advancements in the field of animal diagnostics. The need for proper validation studies of POC devices is highlighted to optimize animal biosecurity.
Dormancy-like Phenotype of Aggregatibacter actinomycetemcomitans: Survival during Famine
Authors: Tjokro Natalia O. , Marks Carolyn B. , Wu Ashley , Chen Casey
Published: May 2024

Microbes frequently experience nutrient deprivations in the natural environment and may enter dormancy. Aggregatibacter actinomycetemcomitans is known to establish long-term infections in humans. This study examined the dormancy-like phenotype of an A. actinomycetemcomitans strain D7S-1 and its isogenic smooth-colony mutant D7SS. A tissue culture medium RPMI-1640 was nutrient-deficient (ND) and unable to support A. actinomycetemcomitans growth. RPMI-1640 amended with bases was nutrient-limited (NL) and supported limited growth of A. actinomycetemcomitans less than the nutrient-enriched (NE) laboratory medium did. Strain D7S-1, after an initial 2-log reduction in viability, maintained viability from day 4 to day 15 in the NL medium. Strain D7SS, after 1-log reduction in viability, maintained viability from day 3 to day 5. In contrast, bacteria in the NE medium were either non-recoverable (D7S-1; >6-log reduction) or continued to lose viability (D7SS; 3-log reduction) on day 5 and beyond. Scanning and transmission electron microscopy showed that A. actinomycetemcomitans in the NL medium formed robust biofilms similar to those in the NE medium but with evidence of stress. A. actinomycetemcomitans in the ND medium revealed scant biofilms and extensive cellular damage. We concluded that A. actinomycetemcomitans grown in the NL medium exhibited a dormancy-like phenotype characterized by minimum growth, prolonged viability, and distinct cellular morphology.
Effect of Probiotic Supplements on the Oral Microbiota—A Narrative Review
Authors: Lundtorp-Olsen Christine , Markvart Merete , Twetman Svante , Belstrøm Daniel
Published: May 2024

Data from systematic reviews and meta-analyses show that probiotics positively impact clinical parameters of oral diseases such as gingivitis, dental caries, and periodontitis. However, the working mechanism of probiotics is not fully understood, but is hypothesized to be mediated by direct and indirect interactions with the oral microbiota and the human host. In the present narrative review, we focused on the microbiological effect of probiotic supplements based on data retrieved from randomized clinical trials (RCTs). In addition, we assessed to what extent contemporary molecular methods have been employed in clinical trials in the field of oral probiotics. Multiple RCTs have been performed studying the potential effect of probiotics on gingivitis, dental caries, and periodontitis, as evaluated by microbial endpoints. In general, results are conflicting, with some studies reporting a positive effect, whereas others are not able to record any effect. Major differences in terms of study designs and sample size, as well as delivery route, frequency, and duration of probiotic consumption, hamper comparison across studies. In addition, most RCTs have been performed with a limited sample size using relatively simple methods for microbial identification, such as culturing, qPCR, and DNA–DNA checkerboard, while high-throughput methods such as 16S sequencing have only been employed in a few studies. Currently, state-of-the-art molecular methods such as metagenomics, metatranscriptomics, and metaproteomics have not yet been used in RCTs in the field of probiotics. The present narrative review revealed that the effect of probiotic supplements on the oral microbiota remains largely uncovered. One important reason is that most RCTs are performed without studying the microbiological effect. To facilitate future systematic reviews and meta-analyses, an internationally agreed core outcome set for the reporting of microbial endpoints in clinical trials would be desirable. Such a standardized collection of outcomes would most likely improve the quality of probiotic research in the oral context.
Hive Products: Composition, Pharmacological Properties, and Therapeutic Applications
Authors: Bava Roberto , Castagna Fabio , Lupia Carmine , Poerio Giusi , Liguori Giovanna , Lombardi Renato , Naturale Maria Diana , Bulotta Rosa Maria , Biondi Vito , Passantino Annamaria , Britti Domenico , Statti Giancarlo , Palma Ernesto
Published: May 2024

Beekeeping provides products with nutraceutical and pharmaceutical characteristics. These products are characterized by abundance of bioactive compounds. For different reasons, honey, royal jelly, propolis, venom, and pollen are beneficial to humans and animals and could be used as therapeutics. The pharmacological action of these products is related to many of their constituents. The main bioactive components of honey include oligosaccharides, methylglyoxal, royal jelly proteins (MRJPs), and phenolics compounds. Royal jelly contains jelleins, royalisin peptides, MRJPs, and derivatives of hydroxy-decenoic acid, particularly 10-hydroxy-2-decenoic acid (10-HDA), which possess antibacterial, anti-inflammatory, immunomodulatory, neuromodulatory, metabolic syndrome-preventing, and anti-aging properties. Propolis has a plethora of activities that are referable to compounds such as caffeic acid phenethyl ester. Peptides found in bee venom include phospholipase A2, apamin, and melittin. In addition to being vitamin-rich, bee pollen also includes unsaturated fatty acids, sterols, and phenolics compounds that express antiatherosclerotic, antidiabetic, and anti-inflammatory properties. Therefore, the constituents of hive products are particular and different. All of these constituents have been investigated for their properties in numerous research studies. This review aims to provide a thorough screening of the bioactive chemicals found in honeybee products and their beneficial biological effects. The manuscript may provide impetus to the branch of unconventional medicine that goes by the name of apitherapy.
A New and Rapid LC-MS/MS Method for the Determination of Cysteamine Plasma Levels in Cystinosis Patients
Authors: Simeoli Raffaele , Cairoli Sara , Greco Marcella , Bellomo Francesco , Mancini Alessandro , Rossi Chiara , Dionisi Vici Carlo , Emma Francesco , Goffredo Bianca Maria
Published: May 2024

Cystinosis is a rare lysosomal storage disorder caused by autosomal recessive mutations in the CTNS gene that encodes for the cystine transporter cystinosin, which is expressed on the lysosomal membrane mediating the efflux of cystine. Cysteamine bitartrate is a cystine-depleting aminothiol agent approved for the treatment of cystinosis in children and adults. In this study, we developed and validated a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the determination of cysteamine levels in plasma samples. This LC-MS/MS method was validated according to the European Medicines Agency (EMA)’s guidelines for bioanalytical method validation. An ultra-performance liquid chromatograph (UPLC) coupled with a 6470 mass spectrometry system was used for cysteamine determination. Our validated method was applied to plasma samples from n = 8 cystinosis patients (median, interquartile range (IQR) = 20.5, 8.5–26.0 years). The samples were collected before cysteamine oral administration (pre-dose) and 1 h after (post-dose). Our bioanalytical method fulfilled the regulatory guidelines for method validation. The cysteamine plasma levels in pre-dose samples were 2.57 and 1.50–3.31 μM (median and IQR, respectively), whereas the post-dose samples reported a cysteamine median concentration of 28.00 μM (IQR: 17.60–36.61). Our method allows the rapid determination of cysteamine plasma levels. This method was successfully used in cystinosis patients and, therefore, could be a useful tool for the evaluation of therapy adherence and for future pharmacokinetic (PK) studies involving a higher number of subjects.
Progress of Antimicrobial Mechanisms of Stilbenoids
Authors: Li Xiancai , Li Yongqing , Xiong Binghong , Qiu Shengxiang
Published: May 2024

Antimicrobial drugs have made outstanding contributions to the treatment of pathogenic infections. However, the emergence of drug resistance continues to be a major threat to human health in recent years, and therefore, the search for novel antimicrobial drugs is particularly urgent. With a deeper understanding of microbial habits and drug resistance mechanisms, various creative strategies for the development of novel antibiotics have been proposed. Stilbenoids, characterized by a C6–C2–C6 carbon skeleton, have recently been widely recognized for their flexible antimicrobial roles. Here, we comprehensively summarize the mode of action of stilbenoids from the viewpoint of their direct antimicrobial properties, antibiofilm and antivirulence activities and their role in reversing drug resistance. This review will provide an important reference for the future development and research into the mechanisms of stilbenoids as antimicrobial agents.
In Vitro and In Vivo Evaluation of the Effects of Drug 2c and Derivatives on Ovarian Cancer Cells
Authors: Maddaloni Marianna , Farra Rossella , Dapas Barbara , Felluga Fulvia , Benedetti Fabio , Berti Federico , Drioli Sara , Vidali Mattia , Cemazar Maja , Kamensek Urska , Brancolini Claudio , Murano Erminio , Maremonti Francesca , Grassi Mario , Biasin Alice , Rizzolio Flavio , Cavarzerani Enrico , Scaggiante Bruna , Bulla Roberta , Balduit Andrea , Ricci Giuseppe , Zito Gabriella , Romano Federico , Bonin Serena , Azzalini Eros , Baj Gabriele , Tierno Domenico , Grassi Gabriele
Published: May 2024

Background: The identification of novel therapeutic strategies for ovarian cancer (OC), the most lethal gynecological neoplasm, is of utmost urgency. Here, we have tested the effectiveness of the compound 2c (4-hydroxy-2,6-bis(4-nitrobenzylidene)cyclohexanone 2). 2c interferes with the cysteine-dependent deubiquitinating enzyme (DUB) UCHL5, thus affecting the ubiquitin-proteasome-dependent degradation of proteins. Methods: 2c phenotypic/molecular effects were studied in two OC 2D/3D culture models and in a mouse xenograft model. Furthermore, we propose an in silico model of 2c interaction with DUB-UCHL5. Finally, we have tested the effect of 2c conjugated to several linkers to generate 2c/derivatives usable for improved drug delivery. Results: 2c effectively impairs the OC cell line and primary tumor cell viability in both 2D and 3D conditions. The effectiveness is confirmed in a xenograft mouse model of OC. We show that 2c impairs proteasome activity and triggers apoptosis, most likely by interacting with DUB-UCHL5. We also propose a mechanism for the interaction with DUB-UCHL5 via an in silico evaluation of the enzyme-inhibitor complex. 2c also reduces cell growth by down-regulating the level of the transcription factor E2F1. Eventually, 2c activity is often retained after the conjugation with linkers. Conclusion: Our data strongly support the potential therapeutic value of 2c/derivatives in OC.
Compact Quantum Random Number Generator Based on a Laser Diode and a Hybrid Chip with Integrated Silicon Photonics
Authors: Wang Xuyang , Zheng Tao , Jia Yanxiang , Huang Jin , Zhu Xinyi , Shi Yuqi , Wang Ning , Lu Zhenguo , Zou Jun , Li Yongmin
Published: May 2024

In this study, a compact and low-power-consumption quantum random number generator (QRNG) based on a laser diode and a hybrid chip with integrated silicon photonics is proposed and verified experimentally. The hybrid chip’s size is 8.8 × 2.6 × 1 mm3, and the power of the entropy source is 80 mW. A common-mode rejection ratio greater than 40 dB was achieved using an optimized 1 × 2 multimode interferometer structure. A method for optimizing the quantum-to-classical noise ratio is presented. A quantum-to-classical noise ratio of approximately 9 dB was achieved when the photoelectron current is 1 μA using a balance homodyne detector with a high dark current GeSi photodiode. The proposed QRNG has the potential for use in scenarios of moderate MHz random number generation speed, with low power, small volume, and low cost prioritized.
Body Condition in Small Ruminants—Effects of Nutrition on the Hypothalamic–Pituitary–Gonad Axis and Ovarian Activity That Controls Reproduction
Authors: Chaves Ana Sofia , Silva Filipe , Valentim Ramiro , Quintas Hélder
Published: May 2024

Nutritional status plays a vital role in regulating ovary activity. This regulation is mediated by the hypothalamus–pituitary–gonad axis and by effects exerted directly on the ovary. Therefore, to achieve the best reproductive performance, it is essential to know how the nutritional status affects the secretion of GnRH, gonadotrophins, and sex steroid hormones. Adequate body reserves and energy balance are critical for optimal reproductive performance in sheep and goats. However, over- or under-conditioned animals experience issues like extended anestrus, irregular ovarian cycles, and reduced conception. Body condition scoring allows for the evaluation of the relationships between adiposity, nutritional status, and fertility. Acute feed deficits briefly stimulate processes, but chronic restrictions suppress pulsatile LH release, disrupting ovarian function. The process of follicle development is a very complex one which involves intricate interactions between the pituitary gonadotrophins and metabolic hormones as well as between the locally produced factors by the ovarian somatic and germ cells including the IGF system and the TGF-β superfamily members. Genotype and nutrition are factors that have an impact on follicular development, and seasonal factors are also involved. This review will give a brief overview on how the body condition can be evaluated and the effects of nutrition on the hypothalamus–pituitary–gonad axis and ovarian activity, which are responsible for reproductive regulation. This paper presents a clear and reasonable summary of the pathway that runs from the nutritional status of small ruminants to ovarian activity through the hypothalamic–pituitary–gonadal axis. This review summarizes methods for body condition evaluation in small ruminants and evidence regarding acute versus prolonged nutritional impacts on the hypothalamic–pituitary–gonadal axis and ovarian activity controlling reproduction.
Ethnomedicinal Plants and Herbal Preparations Used by Rural Communities in Tehsil Hajira (Poonch District of Azad Kashmir, Pakistan)
Authors: Jabeen Tahira , Amjad Muhammad Shoaib , Ahmad Khalid , Bussmann Rainer W. , Qureshi Huma , Vitasović-Kosić Ivana
Published: May 2024

The present study emphasizes the importance of documenting ethnomedicinal plants and herbal practices of the local rural communities of Tehsil Hajira (Pakistan). The aim was to document, explore and quantify the traditional ethnomedicinal knowledge. Ethnobotanical data were collected using semi-structured questionnaires and analyzed using various quantitative indices. The results showed that 144 medicinal plant species from 70 families and 128 genera play an important role in herbal preparations. The most common type of preparation was powder (19.0%), followed by paste (16.7%), aqueous extract (15.7%), decoction (14.7%) and juice (11.0%). Fragaria nubicola (0.94) and Viola canescens (0.93) had the highest relative frequency of mention (RFC), while Berberis lycium (1.22) and Fragaria nubicola (1.18) had the highest use value (UV). Geranium wallichianum (85.5), Ligustrum lucidum (83) and Indigofera heterantha (71.5) were the most important species in the study area with the highest relative importance (RI) value. The diseases treated were categorized into 17 classes, with diseases of the digestive system and liver having the highest Informant Consensus Factor (ICF) value, followed by diseases of the oropharynx and musculoskeletal system. Important plants mentioned for the treatment of various diseases of the gastrointestinal tract are Zanthoxylum alatum, Berberis lycium, Mentha longifolia, Punica granatum, Rubus ellipticus and Viola canescens. New applications of rarely documented plants from this area are: Oxalis corniculata paste of the whole plant to treat vitiligo, Carthamus tinctorius flowers to treat chicken pox, Dioscorea deltoidea tuber powder to treat productive cough, Inula cappa root decoction to treat miscarriage, Habenaria digitata tuber juice for the treatment of fever, Viola canescens leaves and flowers for the treatment of sore throat and Achillea millefolium root and leaf juice for the treatment of pneumonia. These plants may contain interesting biochemical compounds and should be subjected to further pharmacological studies to develop new drugs. Traditional medicinal knowledge in the area under study is mainly limited to the elderly, traditional healers and midwives. Therefore, resource conservation strategies and future pharmacological studies are strongly recommended.
Isolation of a Marker Olean-12-en-28-butanol Derivative from Viscum continuum E. Mey. Ex Sprague and the Evaluation of Its Antioxidant and Antimicrobial Potentials
Authors: Mapfumari Sipho , Matseke Buang , Bassey Kokoette
Published: May 2024

Viscum continuum E. Mey. Ex Sprague (Mistletoe) is a semi-parasitic plant that grows on the branches of other trees with reported numerous biological activities. This study was aimed at isolating a compound/s that will be used as a standard reference for quality control of South African-based commercialized mistletoe products and to further perform antioxidant and antimicrobial tests on the isolated compound. A dried sample of mistletoe was ground and extracted successively with hexane, dichloromethane (DCM), acetone and methanol using a serial exhaustive cold maceration procedure. The compound was isolated using column chromatography, and its chemical structure was elucidated using two-dimensional nuclear magnetic resonance (2D NMR) and ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS). The antioxidant activity of the compound was determined using DPPH, hydrogen radical scavenging activity and reducing power assays, whereas antimicrobial activity was assessed using the minimum inhibitory concentration (MIC) method. Subjection of the DCM extract to column chromatography resulted in the isolation of a compound elucidated as olean-12-en-28-butanol-1-one, 3-hydroxy-4,4,10, 14, 20-pentamethyl (D4). Both the DPPH, H2O2 radical scavenging activity and reducing power assays revealed a significant antioxidant potential of compound D4 with an IC50 of 0.701 mg/mL, lower than that of gallic acid (0.793 mg/mL) for the H2O2 radical scavenging assay. The results also indicated good antibacterial activity of D4 with an IC50 of 0.25 mg/mL, compared to ciprofloxacin with an IC50 of 0.0039 mg/mL, against two Gram-negative (Pseudomonas aeruginosa, Escherichia coli) and three Gram-positive (Streptococcus pyogenes, Bacillus cereus and Staphylococcus aureus) bacteria. This study is the first to report on the isolation of the olean-12-en-28-butanol derivative from mistletoe of the South African ecotype.
Octoploids Show Enhanced Salt Tolerance through Chromosome Doubling in Switchgrass (Panicum virgatum L.)
Authors: Ye Jiali , Fan Yupu , Zhang Hui , Teng Wenjun , Teng Ke , Wu Juying , Fan Xifeng , Wang Shiwen , Yue Yuesen
Published: May 2024

Polyploid plants often exhibit enhanced stress tolerance. Switchgrass is a perennial rhizomatous bunchgrass that is considered ideal for cultivation in marginal lands, including sites with saline soil. In this study, we investigated the physiological responses and transcriptome changes in the octoploid and tetraploid of switchgrass (Panicum virgatum L. ‘Alamo’) under salt stress. We found that autoploid 8× switchgrass had enhanced salt tolerance compared with the amphidiploid 4× precursor, as indicated by physiological and phenotypic traits. Octoploids had increased salt tolerance by significant changes to the osmoregulatory and antioxidant systems. The salt-treated 8× Alamo plants showed greater potassium (K+) accumulation and an increase in the K+/Na+ ratio. Root transcriptome analysis for octoploid and tetraploid plants with or without salt stress revealed that 302 upregulated and 546 downregulated differentially expressed genes were enriched in genes involved in plant hormone signal transduction pathways and were specifically associated with the auxin, cytokinin, abscisic acid, and ethylene pathways. Weighted gene co-expression network analysis (WGCNA) detected four significant salt stress-related modules. This study explored the changes in the osmoregulatory system, inorganic ions, antioxidant enzyme system, and the root transcriptome in response to salt stress in 8× and 4× Alamo switchgrass. The results enhance knowledge of the salt tolerance of artificially induced homologous polyploid plants and provide experimental and sequencing data to aid research on the short-term adaptability and breeding of salt-tolerant biofuel plants.
Ascent and Attachment in Pea Plants: A Matter of Iteration
Authors: Guerra Silvia , Bruno Giovanni , Spoto Andrea , Panzeri Anna , Wang Qiuran , Bonato Bianca , Simonetti Valentina , Castiello Umberto
Published: May 2024

Pea plants (Pisum sativum L.) can perceive the presence of potential supports in the environment and flexibly adapt their behavior to clasp them. How pea plants control and perfect this behavior during growth remains unexplored. Here, we attempt to fill this gap by studying the movement of the apex and the tendrils at different leaves using three-dimensional (3D) kinematical analysis. We hypothesized that plants accumulate information and resources through the circumnutation movements of each leaf. Information generates the kinematical coordinates for the final launch towards the potential support. Results suggest that developing a functional approach to grasp movement may involve an interactive trial and error process based on continuous cross-talk across leaves. This internal communication provides evidence that plants adopt plastic responses in a way that optimally corresponds to support search scenarios.
Identification and Functional Verification of the Glycosyltransferase Gene Family Involved in Flavonoid Synthesis in Rubus chingii Hu
Authors: Shi Yujie , Chen Zhen , Shen Mingkai , Li Qianfan , Wang Shunli , Jiang Jingyong , Zeng Wei
Published: May 2024

Glycosylation is catalyzed by UDP-glycosyltransferase (UGT) and plays an important role in enriching the diversity of flavonoids. Rubus plants contain a lot of natural flavonoid glycosides, which are important plants with a homology of medicine and food. However, information about the Rubus UGT gene family is very limited. In this study, we carried out genome-wide analysis and identified the 172, 121, 130, 121 UGT genes in R. chingii, R. corchorifolius, R. idaeus, and R. occidentalis, respectively, and divided them into 18 groups. The analysis of the protein motif and gene structure showed that there were structural and functional conservations in the same group, but there were differences among different groups. Gene replication analysis showed that raspberry and dicotyledons had a higher homology. The expansion of the UGTs gene family was mainly driven by tandem replication events, and experienced purified selection during the long evolution of the raspberry. Cis-acting element analysis showed that they were related to plant growth and development, hormone regulation, and stress response. In addition, according to a comprehensive analysis of the co-expression network constructed by transcriptome data and phylogenetic homology, RchUGT169 was identified as a flavonoid glucosyltransferase. Through the transient expression in tobacco, it was verified that RchUGT169 could catalyze the conversion of kaempferol and quercetin to the corresponding flavonoid glycosides. In conclusion, this research enriched the understanding of the diversity of UGTs in Rubus and determined that RcUGT169 can catalyze flavonoids.
Optimizing Transport Carrier Free All-Polymer Solar Cells for Indoor Applications: TCAD Simulation under White LED Illumination
Authors: Salem Marwa S. , Okil Mohamed , Shaker Ahmed , Abouelatta Mohamed , Aledaily Arwa N. , Al-Dhlan Kawther A. , Alshammari Mohammad T. , Salah Mostafa M. , El Sabbagh Mona
Published: May 2024

This work inspects the utilization of all-polymer solar cells (APSCs) in indoor applications under LED illumination, with a focus on boosting efficiency through simulation-based design. The study employs a SCAPS TCAD device simulator to investigate the performance of APSCs under white LED illumination at 1000 lux, with a power density of 0.305 mW/cm2. Initially, the simulator is validated against experimental results obtained from a fabricated cell utilizing CD1:PBN-21 as an absorber blend and PEDOT:PSS as a hole transportation layer (HTL), where the initial measured efficiency is 16.75%. The simulation study includes an examination of both inverted and conventional cell structures. In the conventional structure, where no electron transportation layer (ETL) is present, various materials are evaluated for their suitability as the HTL. NiO emerges as the most promising HTL material, demonstrating the potential to achieve an efficiency exceeding 27%. Conversely, in the inverted configuration without an HTL, the study explores different ETL materials to engineer the band alignment at the interface. Among the materials investigated, ZnS emerges as the optimal choice, recording an efficiency of approximately 33%. In order to reveal the efficiency limitations of these devices, the interface and bulk defects are concurrently investigated. The findings of this study underscore the significance of careful material selection and structural design in optimizing the performance of APSCs for indoor applications.
Preparation of Polyaniline-Modified Cellulose/PDMS Composite Triboelectric Material and Application of Its Pretreatment in MOW Pulp
Authors: Sun Xiaoping , Wei Yuhe , Sun Yanfen , Yuan Juan , Chen Haoqiu , Chen Zhuo , Wang Mengyang , Luo Lianxin
Published: May 2024

Self-powered electronic equipment has rapidly developed in the fields of sensing, motion monitoring, and energy collection, posing a greater challenge to triboelectric materials. Triboelectric materials need to enhance their electrical conductivity and mechanical strength to address the increasing demand for stability and to mitigate unpredictable physical damage. In this study, polyaniline-modified cellulose was prepared by means of in situ polymerization and compounded with polydimethylsiloxane, resulting in a triboelectric material with enhanced strength and conductivity. The material was fabricated into a tubular triboelectric nanogenerator (TENG) (G-TENG), and an electrocatalytic pretreatment of mixed office waste paper (MOW) pulp was performed using papermaking white water as the flowing liquid to improve the deinking performance. The electrical output performance of G-TENG is highest at a flow rate of 400 mL/min, producing a voltage of 22.76 V and a current of 1.024 μA. Moreover, the deinking effect of MOW was enhanced after the electrical pretreatment. This study explores the potential application of G-TENG as a self-powered sensor power supply and emphasizes its prospect as an energy collection device.