bluuebunny/crossref_metadata_2025 huggingface dataset:
An In Vitro RNA Editing-Based Reporter Assay for Transcriptional Activity of Therapeutic Gene in Gene Therapy Products
Authors: Yu Lei , Zhou Yong , Wang Guangyu , Fu Jianning , Fu Zhihao , Liang Chenggang , Wang Junzhi
Published: November 2024

The expression of therapeutic genes is critical for the efficacy of gene therapy products. However, existing methods such as immunological analysis at the protein level or reverse-transcription PCR at the RNA level are unable to accurately quantify the expression activity of the target gene. Herein, an in vitro RNA editing-based reporter assay was developed to detect specific mRNA. The designed sensor RNA could specifically identify the target mRNA, and the reporter gene was activated in a dose-dependent manner because of RNA editing mediated by endogenous adenosine deaminases acting on RNA. Of note, all sensors that targeted different regions, including the gene of interest, tag sequence, and 3′ untranslated region, showed a dose-dependent response pattern. The sensor reporter assay, which was used for quantifying the transcriptional activity of recombinant adeno-associated virus-based gene therapy products, revealed excellent performance in terms of assay specificity, precision (inter-assay relative standard deviation < 15%), accuracy (90–115% recovery), and linearity (R2 > 0.99). The reporter assay could also be employed for other gene therapy vectors, including mRNA and recombinant lentivirus. Thus, a robust and reliable platform was developed for assessing the transcriptional activity of therapeutic genes, thereby offering a powerful tool for the quality control of gene therapy products.
Recent Advances in Rechargeable Zn-Air Batteries
Authors: Zhao Hui
Published: November 2024

Rechargeable Zn-air batteries are considered to be an effective energy storage device due to their high energy density, environmental friendliness, and long operating life. Further progress on rechargeable Zn-air batteries with high energy density/power density is greatly needed to satisfy the increasing energy conversion and storage demands. This review summarizes the strategies proposed so far to pursue high-efficiency Zn-air batteries, including the aspects of the electrocatalysts (from noble metals to non-noble metals), the electrode chemistry (from the oxygen evolution reaction to the organic oxidation reaction), electrode engineering (from powdery to free-standing), aqueous electrolytes (from alkaline to non-alkaline) and the battery configuration (from liquid to flexible). An essential evaluation of electrochemistry is highlighted to solve the challenges in boosting the efficiency of rechargeable metal-air batteries. In the end, the perspective on current challenges and future research directions to promote the industrial application of rechargeable Zn-air batteries is provided.
Optimization Strategies of Hybrid Lithium Titanate Oxide/Carbon Anodes for Lithium-Ion Batteries
Authors: Apostolopoulou Maria , Vernardou Dimitra , Passerini Stefano
Published: November 2024

Lithium-ion batteries, due to their high energy density, compact size, long lifetime, and low environmental impact, have achieved a dominant position in everyday life. These attributes have made them the preferred choice for powering portable devices such as laptops and smartphones, power tools, and electric vehicles. As technology advances rapidly, the demand for even more efficient energy storage devices continues to rise. In lithium-ion batteries, anodes play a crucial role, with lithium titanate oxide standing out as a highly promising material. This anode is favored for its exceptional cycle stability, safety features, and fast charging capabilities. The impressive cycle stability of lithium titanate oxide is largely due to its zero-strain nature, meaning it undergoes minimal volume changes during lithium-ion insertion and extraction. This stability enhances the anode’s durability, leading to longer battery life. In addition, the lithium titanate oxide anode operates at a voltage of approximately 1.55 V vs. Li+/Li, significantly reducing the risk of dendrite formation, a major safety concern that can cause short circuits and fires. The material’s spinel structure, with its large active surface area, further allows fast electron transfer and ion diffusion, facilitating fast charging. This review explores the characteristics of lithium titanate oxide, the various synthesis methods employed, and its integration with carbon materials to enhance cycle stability, coulombic efficiency, and safety. It also proposes strategies for optimizing lithium titanate oxide properties to create sustainable anodes with reduced environmental impact using eco-friendly routes.
Synthesis of TiO2-ZnO n-n Heterojunction with Excellent Visible Light-Driven Photodegradation of Tetracycline
Authors: Zhang Ying , Bo Xinkang , Zhu Tao , Zhao Wei , Cui Yumin , Chang Jianguo
Published: November 2024

Zinc oxide-based photocatalysts with non-toxicity and low cost are promising candidates for the degradation of tetracycline. Despite the great success achieved in constructing n-n-type ZnO-based heterojunctions for the degradation of tetracycline under full-spectrum conditions, it is still challenging to realize rapid and efficient degradation of tetracycline under visible light using n-n-type ZnO-based heterojunctions, as they are constrained by the quick recombination of electron–hole pairs in ZnO. Here, we report highly efficient and stable n-n-type ZnO-TiO2 heterojunctions under visible light conditions, with a degradation efficiency reaching 97% at 1 h under visible light, which is 1.2 times higher than that of pure zinc oxide, enabled by constructing an n-n-type heterojunction between ZnO and TiO2 to form a built-in electric field. The photocatalytic degradation mechanism of n-n TiO2-ZnO to tetracycline is also proposed in detail. The demonstration of efficient and stable heterojunction-type ZnO photocatalysts under visible light is an important step toward commercialization and opens up new opportunities beyond conventional ZnO technologies, such as composite ZnO catalysts.
Gold Nanoparticles: Multifunctional Properties, Synthesis, and Future Prospects
Authors: Duman Hatice , Akdaşçi Emir , Eker Furkan , Bechelany Mikhael , Karav Sercan
Published: November 2024

Gold nanoparticles (NPs) are among the most commonly employed metal NPs in biological applications, with distinctive physicochemical features. Their extraordinary optical properties, stemming from strong localized surface plasmon resonance (LSPR), contribute to the development of novel approaches in the areas of bioimaging, biosensing, and cancer research, especially for photothermal and photodynamic therapy. The ease of functionalization with various ligands provides a novel approach to the precise delivery of these molecules to targeted areas. Gold NPs’ ability to transfer heat and electricity positions them as valuable materials for advancing thermal management and electronic systems. Moreover, their inherent characteristics, such as inertness, give rise to the synthesis of novel antibacterial and antioxidant agents as they provide a biocompatible and low-toxicity approach. Chemical and physical synthesis methods are utilized to produce gold NPs. The pursuit of more ecologically sustainable and economically viable large-scale technologies, such as environmentally benign biological processes referred to as green/biological synthesis, has garnered increasing interest among global researchers. Green synthesis methods are more favorable than other synthesis techniques as they minimize the necessity for hazardous chemicals in the reduction process due to their simplicity, cost-effectiveness, energy efficiency, and biocompatibility. This article discusses the importance of gold NPs, their optical, conductivity, antibacterial, antioxidant, and anticancer properties, synthesis methods, contemporary uses, and biosafety, emphasizing the need to understand toxicology principles and green commercialization strategies.
A Tuneable and Easy-to-Prepare SERS Substrate Based on Ag Nanorods: A Versatile Tool for Solution and Dry-State Analyses
Authors: Longoni Margherita , Zucca Sofia , Bruni Silvia
Published: November 2024

Surface-enhanced Raman spectroscopy is a powerful technique for the ultra-sensitive detection of organic analytes. In this paper, the preparation of SERS substrates based on silver nanorods (AgNRs) is proposed, exploiting a simple protocol which does not require complex procedures and/or sophisticated and expensive instrumentation. For this purpose, various syntheses of AgNRs were tested, and the best one for preparing the SERS active substrate proved to be the one which does not involve surfactants as nanoparticle stabilizers. The plasmonic properties of the selected substrate can be modified based on the concentration of the deposited nanoparticles, allowing for the experimentation of different excitation wavelengths. Positive results were obtained on reference solutions of three natural dyes of historical interest using both green exciting radiation (532 nm) and two near-infrared ones (785 and 850 nm; the latter is combined with the SSE™ technology for further fluorescence quenching). Furthermore, the substrates of AgNRs were found to be suitable for SERS measurements even in dry-state conditions, i.e., only exploiting the electromagnetic interaction between the nanostructured substrate and the dye molecules absorbed onto a wool fibre.
Physical Activity and Eating Habits of Polish Navy Soldiers and Border Guard Officers—A Comparative Analysis
Authors: Tomczak Andrzej , Anyżewska Anna , Lepionka Tomasz , Bolczyk Izabela , Grudniewski Tomasz , Gładysz Iwona , Kruszewski Artur , Bertrandt Jerzy
Published: November 2024

Background: Physical fitness and a healthy body mass are important predictors of a good performance of military tasks. The purpose of this study was to assess the physical activity level and nutrition, in terms of the frequency of consumption of individual food groups, of Polish Navy soldiers and Maritime Unit of the Border Guard officers. Materials and Methods: This study was conducted on 131 Polish Navy soldiers aged 33.1 ± 6.3 years old and 132 Maritime Unit of the Border Guard officers aged 38.6 ± 5.5 years old. In order to carry out research on physical activity, the International Physical Activity Questionnaire was used. Eating habits were assessed based on a Food Frequency Questionnaire for 61 groups of food products. Results: Over 80% of the soldiers and officers studied indicated high levels of physical activity. Only 8.2% of soldiers and 4.3% of officers indicated a low level of physical activity. Of the 61 food product groups analyzed, significant differences were found in the frequency of consumption of 17 products. These differences concerned almost all groups (except dairy products and eggs). Conclusions: To summarize, soldiers and officers presented high and moderate levels of physical activity. Taking into account the demonstrated frequent consumption of high-energy and high-fat products, such as sausages and red meat, as well as margarine, mayonnaise, and sugar, with the low frequency of fruit and vegetable consumption in both studied groups, it is advisable to conduct training among soldiers and officers in the field of health education.
Nutritional, Metabolic, and Inflammatory Alterations in Children with Chylous Effusion in the Postoperative Period of Cardiac Surgery: A Descriptive Cohort
Authors: Silva Sidney V. , Hortencio Tais D. R. , Teles Lidiane O. S. , Esteves Alexandre L. , Nogueira Roberto J. N.
Published: November 2024

Objective: The occurrence of chylous effusion in children undergoing cardiac surgery is progressively increasing due to technical advances that have led to a rise in the number of surgeries. In this context, the objective was to describe the clinical profile of a cohort of patients at the time of chylous effusion diagnosis. Methods: A retrospective cohort analysis was conducted between January 2011 and July 2023, involving 23 patients, aged 0 to 18 years, treated at a quaternary university hospital in southeastern Brazil. Data were obtained from the follow-up records of the Multidisciplinary Nutritional Therapy Team (MNTT) for patients who received nutritional support after developing chylous effusion in the postoperative period of cardiac surgery. Results: The younger population predominated (median age of 6 months), with a high prevalence of malnutrition (60.9%). At the time of chylous effusion diagnosis, 83% had lymphopenia, and 74% had hypoalbuminemia. The longer the time elapsed after surgery for the onset of chylous effusion, the lower the HDL cholesterol, the lower the albumin levels, the greater the surgical complexity, the younger the patient, and the lower their weight. Hypocalcemia occurred in nearly half of the sample and hypophosphatemia in 26% of the analyzed cases. Conclusions: There was a notable presence of lymphopenia, hypoalbuminemia, and low HDL cholesterol, as well as a high incidence of mineral imbalances, particularly hypocalcemia and hypophosphatemia, which, if untreated, may lead to unfavorable outcomes. Therefore, clinical and laboratory monitoring of children in the postoperative period of cardiac surgery is important and can aid in the early diagnosis of chylous effusion and, consequently, in the timely initiation of treatment.
Understanding the Food and Nutrition Insecurity Drivers in Some Emergency-Affected Countries in the Eastern Mediterranean Region from 2020 to 2024
Authors: Al Sharjabi Salwa Jamal , Al Jawaldeh Ayoub , Hassan Ola El Hajj , Dureab Fekri
Published: November 2024

This research seeks to enhance the understanding of the multifaceted drivers of food and nutrition insecurity in emergency-affected countries within the Eastern Mediterranean region and investigate the dynamics of food and nutrition security in countries facing emerging emergencies. This is a descriptive aim to determine the key factors and challenges affecting food security and nutrition status in ten countries in the Eastern Mediterranean region (Afghanistan, Djibouti, Iraq, Lebanon, Pakistan, Palestine (Gaza Strip), Somalia, Sudan, Syria, and Yemen). The research reveals that all selected countries experienced severe levels of food insecurity, with many reaching Phase 3 or above according to the IPC classification. In 2020, Afghanistan and Yemen were particularly hard-hit, with food insecurity affecting 42% and 45% of their populations; in 2024 in Gaza and Sudan, the same figures were 93% and 54% of the population, respectively, representing worse food insecurity crises in the region. Somalia, Sudan, and Djibouti also faced significant food insecurity rates. Many key drivers of food security are standard in most countries, and the linkage between food insecurity and malnutrition levels has a similar trend in almost all countries. However, none of the countries achieved all the 2025 global nutrition targets, while some reached one or two targets. Reaching sustainable development goals is still challenging in these countries since nutrition and food security levels, included in many goals, have not yet been reached. Food security and malnutrition in emergency-affected countries are driven by conflict, political instability, natural disasters, and socioeconomic conditions, which disrupt agricultural activities and infrastructure, exacerbating these challenges. To address these issues, we recommend a multisectoral approach, conflict resolution, climate-smart agriculture, integration of emergency responses with long-term strategies, and strengthening health and nutrition information systems.
Pomegranate Peel Extract Mitigates Diarrhea-Predominant Irritable Bowel Syndromes via MAPK and NF-κB Pathway Modulation in Rats
Authors: Zhang Yannan , Huang Sijuan , Zhang Shuai , Hao Zhihui , Shen Jianzhong
Published: November 2024

Background: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common chronic functional gastrointestinal disorder that causes diarrheal and intestinal barrier disruptions. Although pomegranate peel extract (PPE) has been reported for the treatment of diarrheal and intestinal inflammation, its effectiveness and mechanisms specifically for the treatment of IBS-D remain unknown. Objectives: This study aimed to explore the therapeutic effect of PPE on IBS-D and elucidate its underlying mechanisms. Methods: A high-fat diet, restraint stress, and senna gavage were combined to establish a rat model mimicking IBS-D, to evaluate the therapeutic effects of PPE. Network pharmacology analysis, serum medicinal chemistry, and transcriptomics were employed to investigate potential downstream signaling pathways. Findings were further validated through molecular docking and Western blot analysis. Results: The findings revealed that PPE significantly improved the symptoms of IBS-D, ameliorated intestinal inflammation, and promoted intestinal barrier function. The target genes in the MAPK and NF-κB signaling pathways were significantly enriched and down-regulated. Molecular docking and Western blot assays were performed to verify that PPE had a high affinity for the protein candidates in these pathways, and significantly down-regulated the expression of p-IκB, p-p65, p-JNK, p-p38, and p-ERK1/2. Conclusions: The present study is the first to demonstrate that PPE alleviates diarrheal and intestinal damage in IBS-D, potentially by inhibiting MAPK and NF-κB signaling pathways. These findings suggest that PPE may provide a novel therapeutic option for IBS-D.
Suppressive Effects of Geoje Raspberry (Rubus tozawae Nakai ex J.Y. Yang) on Post-Menopausal Osteoporosis via Its Osteogenic Activity on Osteoblast Differentiation
Authors: Hong Soyeon , Kwon Jaeyoung , Song Sungmin , Park InWha , Jung Da Seul , Saruul Erdenebileg , Nho Chu Won , Kwon Hak Cheol , Yoo Gyhye
Published: November 2024

Background: Osteoporosis is a metabolic bone disease with a high mortality rate due to non-traumatic fractures. The risk of osteoporosis is increasing globally due to an increasing aging population. Current therapies are limited to delaying disease progression. Recently, the need to discover foods with osteogenic activity for the prevention and treatment of osteoporosis has been emphasized. We focused on bone formation via osteoblast differentiation, considering bone formation and resorption during bone homeostasis. Rubus tozawae Nakai ex J. Y. Yang (RL, Geoje raspberry) is a deciduous subshrub that has been traditionally eaten for its fruit. Methods and Results: We identified the third subfraction of n-hexane fraction (RL-Hex-NF3) of RL, an endemic Korean plant with osteogenic activity, which increased bone density in ovariectomized mice, a representative animal model of osteoporosis, via the depletion of female hormones, which resulted from the increase in the osteoblast population. RL-Hex-NF3 induced osteoblast differentiation and the expression of osteogenic markers in MC3T3-E1 pre-osteoblasts. Seven compounds were identified from RL-Hex-NF3 using NMR spectroscopy. Of these, three compounds, namely, 3β-hydroxy-18α,19α-urs-20-en-28-oic acid, betulinic acid, and (1S,6R,7S)-muurola-4,10(14)-diene-15-ol, showed strong osteogenic activity. Conclusions: RL-Hex-NF3 and its compounds suppress bone loss via their osteogenic properties, suggesting that they could be a potent candidate to treat osteoporosis.
The Therapeutic Management of Chemical and Herbal Medications on Uric Acid Levels and Gout: Modern and Traditional Wisdom
Authors: Lin Zhijian , Gupta Jeetendra Kumar , Maqbool Mohsin , Kumar Krishan , Sharma Ayushi , Wahi Nitin
Published: November 2024

Background: Gout is a chronic inflammatory condition characterized by elevated uric acid levels in the blood, which can precipitate acute gout attacks in individuals with genetic susceptibility, existing medical conditions, and dietary influences. Genetic predispositions, comorbid medical conditions, nutritional choices, and environmental factors increasingly recognize the multifactorial etiology of the disease. Methods: Recent research has highlighted the potential of phytochemicals, particularly flavonoids, saponins, and alkaloids, to manage hyperuricemia (HUA) and its associated complications. Results: Plant’s natural compounds have garnered attention for their anti-inflammatory, antioxidant, and uric acid-lowering properties, suggesting their role in alternative and complementary medicine. Phytochemicals have demonstrated promise in mitigating gout symptoms and potentially modifying the disease course by addressing different aspects of hyperuricemia and inflammation. Herbal remedies, with their complex phytochemical profiles, offer a unique advantage by potentially complementing conventional pharmacological treatments. The integration of herbal therapies with standard medications could lead to enhanced therapeutic outcomes through synergistic effects, optimizing disease management, and improving patient quality of life. Conclusions: This review examines the current understanding of the multifaceted etiology of gout, explores the role of phytochemicals in managing hyperuricemia, and discusses the potential benefits of combining herbal remedies with conventional treatments to improve patient care and therapeutic efficacy.
Innovative Epicardial Bigels Containing Amiodarone Hydrochloride: Pharmacotechnical and Analytical Characterization
Authors: Pintea Cezara , Vlad Robert-Alexandru , Antonoaea Paula , Rédai Emőke Margit , Bîrsan Magdalena , Barabás Enikő-Csilla , Manea Andrei , Pușcaș Iulia Alexandra , Ciurba Adriana
Published: November 2024

Background/Objectives: The search for novel ways of providing treatment also targets the development of formulations used in drug delivery. Among the important characteristics of pharmaceutical gels are their ability to penetrate membranes, their capability to offer rapid response, and their capacity to avoid the hepatic metabolization route followed by many drugs. Bigels combine the advantages of both hydrogels and oleogels, creating a biphasic system that might improve the solubility of amiodarone in water, which is otherwise poorly soluble. This study aimed to succeed in formulating stable amiodarone hydrochloride bigels (coded from ABG1-ABG6) destined for atrial application and evaluating them from a pharmacotechnical perspective. Methods: Three of the six initial formulations presented stability and underwent studies of spreadability, rheology, drug content, textural properties, and microbiological activity. A statistical analysis was performed on penetrometry and drug assay data. Results: The spreadability varied from 1734.07 mm2 (ABG1) to 2163.85 mm2 (ABG6), while the drug concentration ranged between 1.35 and 1.49% (w/w). The textural profile analysis highlighted superior hardness, cohesiveness, and resilience for ABG6 and higher adhesion for ABG2. Both presented pseudoplastic thixotropic behavior, while a plastic thixotropic flow was registered in the case of ABG1. Conclusions: All three bigels are suitable for amiodarone incorporation; however, the influence of the type of ingredients chosen on the texture and properties of the formulations was reflected in the data gathered upon evaluation.
Cremastrae Pseudobulbus Pleiones Pseudobulbus (CPPP) Against Non-Small-Cell Lung Cancer: Elucidating Effective Ingredients and Mechanism of Action
Authors: Cao Yuxin , Hao Zhuangzhuang , Liu Mengmeng , Xue Jingwen , Wang Yuqing , Wang Yu , Li Jiayuan , Lu Yifan , Wang Chunguo , Shi Jinli
Published: November 2024

Cremastrae Pseudobulbus Pleiones Pseudobulbus (CPPP) is derived from the dried pseudobulb of the orchid family plants Cremastra appendiculata (D.Don) Makino, Pleione bulbocodioides (Franch.) Rolfe, or Pleione yunnanensis Rolfe, and has the properties of clearing heat, detoxification, resolving phlegm, and dispersing nodules. It is frequently used for the treatment of various malignant tumors in clinical practice, especially lung cancer. CPPP is divided into two commercial specifications in the market, Maocigu (MCG) and Bingqiuzi (BQZ). However, owing to a lack of appropriate research strategies, the active ingredients and molecular mechanisms involved have not yet been clarified. This study intended to discover the combination of effective anti-lung-cancer ingredients in CPPP and explore their potential mechanisms of action. In this study, UHPLC-MS fingerprints of MCG and BQZ were established separately. Inhibitory effects on the proliferative viability and migratory ability of A459 and H1299 cells were evaluated as pharmacodynamic indicators. GRA and BCA were used to determine spectrum–effect relationships. Next, the identification and analysis of components of drug-containing serum were performed using UHPLC-Q-Exactive Orbitrap MS. Then, the results of the two analyses were combined to jointly screen out the anti-lung-cancer candidate active monomers of CPPP, and their in vitro activities were verified. Afterward, all effective ingredient combinations of MCG (MCGC) and BQZ (BQZC) were prepared according to their contents in the original medicinal materials. Their anti-lung-cancer activities in vitro and in vivo were compared and verified. Finally, we used the human lung cancer cell line A549 and the Lewis tumor xenograft model to investigate how BQZC would influence autophagy and apoptosis processes and the mechanisms involved. Overall, 11 predominant anti-lung-cancer active ingredients from CPPP were screened. Next, MCGC and BQZC were prepared according to their contents in the original medicinal materials, respectively, and their anti-tumor effects were equivalent to those of the original materials in vitro and in vivo. We found that BQZC could inhibit lung cancer cell growth and induce protective autophagy and apoptosis in lung cancer cells by activating the AMPK–mTOR–ULK1/BMF signaling pathway. These results provide important evidence for the clinical application and deep development of CPPP against tumors.
Is It Time to Start Worrying? A Comprehensive Report on the Three-Year Prevalence of ESBL-Producing Bacteria and Their Trends in Antibiotic Resistance from the Largest University Hospital in Slovakia
Authors: Jalali Yashar , Kološová Andrea , Liptáková Adriána , Kyselovič Ján , Oleárová Anna , Jalali Monika , Payer Juraj
Published: November 2024

Background/Objectives: Over the past few decades, extended-spectrum β-lactamase (ESBL)-producing bacteria have become a great concern in healthcare systems worldwide, imposing large burdens by increasing antimicrobial resistance and patient morbidity. Given the high mortality rates and emergence of multidrug-resistant (MDR) strains, monitoring ESBL prevalence and resistance patterns is crucial. This study aimed to evaluate ESBL-producing Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae over three years, focusing on phenotypic distribution and resistance profiles. Methods: A total of 1599 ESBL-producing bacterial samples were collected and analysed. A panel of 20 antibiotics was tested to determine resistance traits. Data were recorded on phenotypical distribution, isolation types, changes in antibiotic resistance, and the relation of such changes to antibiotic consumption (defined daily dose) from clinical isolates. Results: Phenotypical analysis revealed the minimal presence of the Cefotaximase from Munich (CTX-M) phenotype in E. coli and K. pneumoniae, creating a distinct epidemiological profile compared to global patterns. Shifts in isolation trends, particularly in P. mirabilis, suggest an expected increase in associated-mortality-rate in the coming years. While resistance trends were not statistically significant, MDR and extensively drug-resistant (XDR) strains were identified across all three bacteria. Only meropenem showed consistent 100% efficacy against E. coli, with other antibiotics displaying only partial effectiveness. Conclusions: These findings highlight the need for ongoing surveillance of ESBL-producing bacteria and underscore challenges in managing antibiotic resistance due to limited efficacy of last-resort treatments. The unique phenotypical distribution observed could impact local resistance management strategies in hospital settings in the coming years.
Halloysite Nanotube-Based Delivery of Pyrazolo[3,4-d]pyrimidine Derivatives for Prostate and Bladder Cancer Treatment
Authors: Massaro Marina , Ciani Rebecca , Grossi Giancarlo , Cavallaro Gianfranco , de Melo Barbosa Raquel , Falesiedi Marta , Fortuna Cosimo G. , Carbone Anna , Schenone Silvia , Sánchez-Espejo Rita , Viseras César , Vago Riccardo , Riela Serena
Published: November 2024

Background/Objectives: The development of therapies targeting unregulated Src signaling through selective kinase inhibition using small-molecule inhibitors presents a significant challenge for the scientific community. Among these inhibitors, pyrazolo[3,4-d]pyrimidine heterocycles have emerged as potent agents; however, their clinical application is hindered by low solubility in water. To overcome this limitation, some carrier systems, such as halloysite nanotubes (HNTs), can be used. Methods: Herein, we report the development of HNT-based nanomaterials as carriers for pyrazolo[3,4-d]pyrimidine molecules. To achieve this objective, the clay was modified by two different approaches: supramolecular loading into the HNT lumen and covalent grafting onto the HNT external surface. The resulting nanomaterials were extensively characterized, and their morphology was imaged by high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM). In addition, the kinetic release of the molecules supramolecularly loaded into the HNTs was also evaluated. QSAR studies were conducted to elucidate the physicochemical and pharmacokinetic properties of these inhibitors, and structure-based virtual screening (SBVS) was performed to analyze their binding poses in protein kinases implicated in cancer. Results: The characterization methods demonstrate successful encapsulation of the drugs and the release properties under physiological conditions. Furthermore, QSAR studies and SBVS provide valuable insights into the physicochemical, pharmacokinetic, and binding properties of these inhibitors, reinforcing their potential efficacy. Conclusions: The cytotoxicity of these halloysite-based nanomaterials, and of pure molecules for comparison, was tested on RT112, UMUC3, and PC3 cancer cell lines, demonstrating their potential as effective agents for prostate and bladder cancer treatment.
Comparison Between Simple Batch and Fed-Batch Bioreactor Cultivation of Recombinant BCG
Authors: Mendes Sarah , Gonçalves Maria C. P. , Aiex Vitoria A. P. , Batista Ryhára D. , Zorzete Patrícia , Leite Luciana C. C. , Gonçalves Viviane M.
Published: November 2024

Background/Objectives: Tuberculosis continues to be a significant global health concern, causing 1.3 million deaths in 2022, particularly affecting children under 5 years old. The Bacillus Calmette-Guérin (BCG) vaccine, developed in 1921, remains the primary defense against tuberculosis but requires modernized production methods. The recombinant BCG-pertussis strain shows potential in providing dual protection against tuberculosis and whooping cough, especially for vulnerable newborns, and enhanced efficacy against bladder cancer. Implementing submerged cultivation techniques for rBCG-pertussis production can offer increased productivity and standardization. Methods: This study explores a fed-batch cultivation strategy with pH-stat control to feed L-glutamic acid through the acid pump into 1 L bioreactor. Three pH values were evaluated for fed-batch and a simple batch without pH control was done for comparison. The viable cell concentration was compared before and after freeze-drying samples harvested during the cultures. Results: L-glutamic acid was identified as the preferred substrate for rBCG-pertussis. While the fed-batch strategy did not enhance the maximum specific growth rate compared to simple batch cultivation, it did improve the specific growth rate after day 4 in the pH 7.4-controlled fed-batch cultures, thereby reducing the cultivation time. Fed-batch cultures controlled at three pH levels exhibited lower optical density than the simple batch, although the viable cell counts were similar. Notably, samples harvested after day 8 from the simple batch cultures showed a reduction in CFU/mL after freeze-drying, whereas all fed-batch samples exhibited high recovery of viable cell counts post lyophilization. Conclusions: The additional glutamate supplied to the fed-batch cultures may have protected the cells during the lyophilization process.
Thymoquinone-Incorporated CollaGee Biomatrix: A Promising Approach for Full-Thickness Wound Healing
Authors: Sallehuddin Nusaibah , Hao Looi Qi , Wen Adzim Poh Yuen , Fadilah Nur Izzah Md , Maarof Manira , Fauzi Mh B.
Published: November 2024

Wound infection is the leading cause of delayed wound healing. Despite ongoing research, the ideal treatment for full-thickness skin wounds is yet to be achieved. Skin tissue engineering provides an alternative treatment, with the potential for skin regeneration. Background/Objectives: Previously, we characterized a collagen–gelatin–elastin (CollaGee) acellular skin substitute and evaluated its cytocompatibility. The assessments revealed good physicochemical properties and cytocompatibility with human dermal fibroblasts (HDF). This study aimed to incorporate thymoquinone (TQ) as the antibacterial agent into CollaGee biomatrices and evaluate their cytocompatibility in vitro. Methods: Briefly, dose–response and antibacterial studies were conducted to confirm the antimicrobial activity and identify the suitable concentration for incorporation; 0.05 and 0.1 mg/mL concentrations were selected. Then, the cytocompatibility was evaluated quantitatively and qualitatively. Results: Cytocompatibility analysis revealed no toxicity towards HDFs, with 81.5 + 0.7% cell attachment and 99.27 + 1.6% cell viability. Specifically, the 0.05 mg/mL TQ concentration presented better viability, but the differences were not significant. Immunocytochemistry staining revealed the presence of collagen I, vinculin, and alpha smooth muscle actin within the three-dimensional biomatrices. Conclusions: These results suggest that TQ-incorporated CollaGee biomatrices are a promising candidate for enhancing the main key player, HDF, to efficiently regenerate the dermal layer in full-thickness skin wound healing. Further investigations are needed for future efficiency studies in animal models.
Integrin-Specific Stimuli-Responsive Nanomaterials for Cancer Theranostics
Authors: Taheri Zahra , Mozafari Negin , Moradian Ghazal , Lovison Denise , Dehshahri Ali , De Marco Rossella
Published: November 2024

Background: Cancer is one of the leading causes of death worldwide. The tumor microenvironment makes the tumor difficult to treat, favoring drug resistance and the formation of metastases, resulting in death. Methods: Stimuli-responsive nanoparticles have shown great capacity to be used as a powerful strategy for cancer treatment, diagnostic, as well as theranostic. Nanocarriers are not only able to respond to internal stimuli such as oxidative stress, weakly acidic pH, high temperature, and the high expression of particular enzymes, but also to external stimuli such as light and paramagnetic characteristics to be exploited. Results: In this work, stimulus-responsive nanocarriers functionalized with arginine-glycine-aspartic acid (Arg-Gly-Asp) sequence as well as mimetic sequences with the capability to recognize integrin receptors are analyzed. Conclusions: This review highlights the progress that has been made in the development of new nanocarriers, capable of responding to endogenous and exogenous stimuli essential to combat cancer.
Orthogonal Frequency Division Diversity and Multiplexing for 6G OWC: Principle and Underwater Use Case
Authors: Chen Jiamin , Chen Chen , Zeng Zhihong , Liu Min , Ye Jia , He Cuiwei , Huang Shenjie , Fu H. Y. , Haas Harald
Published: November 2024

In this paper, we, for the first time, propose and demonstrate an orthogonal frequency division diversity and multiplexing (OFDDM) scheme for the sixth-generation (6G) underwater optical wireless communication (UOWC) systems. In OFDDM, the subcarriers are grouped into subblocks; the subcarriers within each subblock transmit the same constellation symbol through diversity transmission, while different subblocks transmit different constellation symbols via multiplexing transmission. As a result, OFDDM can support hybrid diversity and multiplexing transmission simultaneously. Moreover, the combination of subblock interleaving and low-complexity diversity is further proposed to efficiently mitigate the adverse low-pass effect and substantially reduce the computational complexity, respectively. The feasibility of OFDDM adapting to the various transmission conditions in UOWC systems has been verified via both simulations and experiments. Experimental results demonstrate that a striking 106.1% effective bandwidth extension can be obtained using OFDDM in comparison to conventional orthogonal frequency division multiplexing (OFDM) for a fixed spectral efficiency of 1 bit/s/Hz. Furthermore, OFDDM with adaptive bit loading can also gain a remarkable 13.3% capacity improvement compared with conventional OFDM with adaptive bit loading.
Selective Ablation and Laser-Induced Periodical Surface Structures (LIPSS) Produced on (Ni/Ti) Nano Layer Thin Film with Ultra-Short Laser Pulses
Authors: Gaković Biljana , Petrović Suzana , Siogka Christina , Milovanović Dubravka , Momčilović Miloš , Tsibidis George D. , Stratakis Emmanuel
Published: November 2024

The interaction of ultra-short laser pulses (USLP) with Nickel/Titanium (Ni/Ti) thin film has been presented. The nano layer thin film (NLTF), composed of ten alternating Ni and Ti layers, was deposited on silicon (Si) substrate by ion-sputtering. A single and multi-pulse irradiation was performed in air with focused and linearly polarized laser pulses. For achieving selective ablation of one or more surface layers, without reaching the Si substrate, single pulse energy was gradually increased from near the ablation threshold value to an energy value that caused the complete removal of the NLTF. In addition to single-pulse selective ablation, the multi-pulse USLP irradiation and production of laser-induced periodic surface structures (LIPSSs) were also studied. In the presented experiment, we found the optimal combination of accumulated pulse number and pulse energy to achieve the LIPSS formation on the thin film. The laser-induced morphology was examined with optical microscopy, scanning electron microscopy, and optical profilometry. To interpret the experimental observations, a theoretical simulation has been performed to explore the thermal response of the NLTFs after irradiation with single laser pulses.
Reduction in Temperature-Dependent Fiber-Optic Gyroscope Bias Drift by Using Multifunctional Integrated Optical Chip Fabricated on Pre-Annealed LiNbO3
Authors: Karagöz Ercan , Aşık Fatma Yasemin , Gökkavas Mutlu , Akbaş Erkut Emin , Yertutanol Aylin , Özbay Ekmel , Özcan Şadan
Published: November 2024

The refractive index change obtained after annealed proton exchange (APE) in lithium niobate (LiNbO3) crystals depends on both the proton exchange process carried out in hot acid and the structure of the crystals. In devices produced by the APE method, dislocations and lattice defects within the crystal structure are considered to be primary contributors to refractive index discontinuities and waveguide instability. In this study, the effects of pre-annealing LiNbO3 crystals at 500 °C on multifunctional integrated optical chips (MIOCs) were investigated through interferometric fiber-optic gyroscope (IFOG) system-level tests. It was observed that the pre-annealing process resulted in an improvement in the optical throughput of MIOCs (from %34 to %51) and the temperature-dependent bias drift stability of the IFOG (from 0.031–0.038°/h to 0.012–0.019°/h). The angle random walk (ARW) was measured as 0.0056 deg/√h.
Exploring the Inhibitory Potential of Phytosterols β-Sitosterol, Stigmasterol, and Campesterol on 5-Alpha Reductase Activity in the Human Prostate: An In Vitro and In Silico Approach
Authors: Buț Mădălina-Georgiana , Tero-Vescan Amelia , Pușcaș Amalia , Jîtcă George , Marc Gabriel
Published: November 2024

Steroidal 5α-reductase type 2 (S5αR2) is a key enzyme involved in the conversion of testosterone (TST) to dihydrotestosterone (DHT), a crucial process in the development of benign prostatic hyperplasia (BPH). Phytosterols (PSs), natural plant-derived compounds, have been proposed as potential inhibitors of S5αR2, but studies on their efficacy are limited. This study evaluates the inhibitory effects of three PSs (β-sitosterol, stigmasterol, and campesterol) on S5αR2 activity using a combined in vitro and in silico approach. The inhibitory activity of the respective PSs was assessed in vitro, by measuring TST and DHT, while molecular docking and dynamics explored PS interactions with S5αR2’s active site. The in vitro tests indicated significantly higher IC50 values (β-sitosterol, 3.24 ± 0.32 µM; stigmasterol, 31.89 ± 4.26 µM; and campesterol, 15.75 ± 5.56 µM) for PSs compared to dutasteride (4.88 × 10−3 ± 0.33 µM), suggesting a lower efficiency in inhibiting S5αR2. The in silico studies confirmed these observations, explained by the lower binding affinity identified for PSs to the enzyme’s active site in the molecular docking studies and the reduced stability of the interactions with the active site of the enzyme during the molecular dynamics simulations compared to dutasteride. The results suggest that PSs exhibit low-to-negligible inhibitory activity against S5αR2 (µM range) compared to the synthetic inhibitor dutasteride (nM range). Among the three PSs studied, β-sitosterol showed the highest inhibitory activity and the best stability in its interaction with S5αR2, when compared with stigmasterol and campesterol.
Acclimation of the Resurrection Plant Haberlea rhodopensis to Changing Light Conditions
Authors: Georgieva Katya , Mihailova Gergana
Published: November 2024

Resurrection plants present an attractive model for studying the mechanisms of desiccation tolerance. In addition to drought, the presence of light during desiccation is extremely dangerous. In the present study, we investigated the effect of light during the desiccation of shade and sun Haberlea rhodopensis from two different habitats by measuring the changes in electrolyte leakage, malondialdehyde and proline content, and photosynthetic and antioxidant activities. Moreover, the plasticity and acclimation ability of plants to changing light intensities were studied by desiccating shade plants under high light and sun plants under low light. The most significant differences between shade and sun plants were observed under moderate dehydration. Regardless of some decline in PSII activity in sun plants, it was much higher compared to shade plants. The lower PSII efficiency in the latter was accompanied by a higher extent of excitation pressure and consequently significant enhancement in non-photochemical quenching, Y(NPQ), and especially in the fraction of energy that is passively dissipated as heat and fluorescence, Y(NO). The activity of antioxidant enzymes remained high during the desiccation of H. rhodopensis, being higher in the sun compared to shade plants in an air-dried state. In addition, shade and sun plants showed high acclimation capacity when desiccated at opposite light intensities.
Toxicity of Piper hispidinervum Essential Oil to Callosobruchus maculatus and Cowpea Bean Quality
Authors: Ferraz Maria Suely Siqueira , Faroni Lêda Rita D’Antonino , de Sousa Adalberto Hipólito , Heleno Fernanda Fernandes , Silva Marcus Vinicius de Assis , de Alencar Ernandes Rodrigues
Published: November 2024

Essential oils and their major compounds have been studied to protect stored grains, especially for the control of insects. In this context, this research aimed to investigate the fumigation and contact toxicities of the essential oil of Piper hispidinervum C. DC. (Piperaceae) (sin. Piper hispidum Sw.) to Callosobruchus maculatus adult individuals and the effect on insect progeny. We also assessed the essential oil’s effect on stored-cowpea quality. The fumigation bioassay used essential oil at 14.3, 57.1, 100.0, 142.9, and 185.7 µL/L of air, whereas the contact bioassay tested concentrations of 60, 80, 100, 120, and 140 µL/kg. Insect mortality was appraised after four days (fumigation) or one day (contact). In turn, oviposition and emergence rates were evaluated after seven (fumigation) or fifty (contact) days of storage. Grain quality was also analyzed after 50 days of storage. Safrole was confirmed as the primary compound of the essential oil. P. hispidinervum essential oil proved its fumigant and contact toxicities to C. maculatus adult individuals. The concentrations lethal to 50 and 95% of the population were, respectively, 91.23 and 242.59 µL/L of air (fumigation) and 101.51 and 208.52 µL/kg of cowpeas (contact). In both application forms, C. maculatus oviposition and progeny rates declined with the increase in the essential oil concentration. Furthermore, cowpea bean quality was preserved even at sublethal doses.
Assessing the Diversity of Beta vulgaris L. ssp. maritima (Sea Beet) Populations in Egypt
Authors: Abdelhameed Asmaa A. , Amer Wafaa M. , Al Shaye Najla A. , Hassan Mahmoud O. , Hassan Walaa A.
Published: November 2024

Sea beet (Beta vulgaris L. subsp. maritima (L.) Arcang.) is a wild member of the Amaranthaceae family and a progenitor for all the cultivated beets (Beta vulgaris subsp. vulgaris). It is a source of stress-resistant genes, contributing 21 valuable traits to sugar beet through multiple breeding approaches. Despite its importance, the core morphological diversity of sea beet within the Egyptian Mediterranean coastal region has not yet been thoroughly explored. The field observations indicated notable morphological diversity among sea beet populations. This study investigated the morphological diversity of six sea beet populations along with their associated soil and climatic conditions in their primary habitats. Our morphometric investigations identified two varieties: Beta vulgaris subsp. maritima var. glabra, characterized by glabrous, erect, larger basal leaves, and Beta vulgaris subsp. maritima var. pilosa, distinguished by its hairy, prostrate form with smaller basal leaves. These varieties exhibited differences in their spatial distribution, showing high variations at the inter- and intra-population levels as well as the variety level. Soil parameters significantly influenced population morphological variability, which demonstrated a strong positive correlation with soil organic carbon. Our results highlight the need for precise survey and molecular characterization to secure these potential genetic resources from alteration and loss, especially in coastal habitats that are particularly sensitive to future climate change.