bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling the Stress Field in MSLA-Fabricated Photosensitive Resin Components: A Combined Experimental and Numerical Approach
Authors: Oliveira Geraldo Cesar Rosario de , Rosario de Oliveira Vania Aparecida , Alvarado Silva Carlos Alexis , Guidi Erick Siqueira , Silva Fernando de Azevedo
Published: January 2025

This study presents an experimental and numerical investigation into the stress field in cylinders manufactured from photosensitive resin using the Masked Stereolithography (MSLA) technique. For material characterization, tensile and bending test data from resin specimens were utilized. The stress field in resin disks was experimentally analyzed using photoelasticity and Digital Image Correlation (DIC) methods, subjected to compressive loads, according to the cylinder–plane contact model. Images were captured during the experiments using polarizing film and a low-cost CPL lens, coupled to a smartphone. The experimental results were compared with numerical and analytical simulations, where the formation of fringes and regions indicating the direction and magnitude of normal and shear stresses were observed, with variations ranging from 0.6% to 8.2%. The convergence of the results demonstrates the feasibility of using parts produced with commercially available photosensitive resin on non-professional printers for studying contact theory and stress fields. In the future, this methodology is intended to be applied to studies on stress in gears.
Use of Computational Fluid Dynamics (CFD) Methods to Analyze Combustion Chamber Processes at HVOF Spraying and Their Comparison with Experimental Data
Authors: Rakhadilov Bauyrzhan , Muktanova Nazerke , Kengesbekov Aidar , Magazov Nurtoleu
Published: January 2025

This paper discusses the process of high-velocity oxygen fuel (HVOF) spraying with modeling of the gas flow parameters and behavior of WC-Co-Cr powder particles of different fractions (up to 20 µm, 21–35 μm and 36–45 μm). It was found that the temperature of the gas stream reaches a maximum of about 2700 °C, after which it gradually decreases, and the pressure in the combustion chamber (before the exit of gases through the nozzle) reaches maximum values, exceeding 400,000 Pa, and the pressure at the exit of the nozzle stabilizes at about 100,000 Pa, which corresponds to the standard atmospheric pressure. The gas velocity increases to 1300–1400 m/s and then decreases to 400 m/s at a distance of about 150 mm. It was determined that powder particles of the 21–35 µm fraction provide more stable parameters of velocity and temperature. Small particles (up to 20 µm) lose velocity and temperature faster as they advance, which deteriorates the coating quality, which was also experimentally confirmed. All results obtained from the HVOF process modeling fully align with the data from experimental studies.
Guanidines Conjugated with Cell-Penetrating Peptides: A New Approach for the Development of Antileishmanial Molecules
Authors: de Souza João Victor Marcelino , Costa Natalia C. S. , Brasil Maria C. O. Arruda , dos Anjos Luana Ribeiro , de Menezes Renata Priscila Barros , Zampieri Eduardo Henrique , de Lima Jhonatan Santos , Velasquez Angela Maria Arenas , Scotti Luciana , Scotti Marcus Tullius , Graminha Marcia A. S. , Gonzalez Eduardo R. Pérez , Cilli Eduardo Maffud
Published: January 2025

Leishmaniasis is a neglected tropical disease caused by a protozoan of the genus Leishmania, which has visceral and cutaneous forms. The symptoms of leishmaniasis include high fever and weakness, and the cutaneous infection also causes lesions under the skin. The drugs used to treat leishmaniasis have become less effective due to the resistance mechanisms of the protozoa. In addition, the current compounds have low selectivity for the pathogen, leading to various side effects, which results in lower adherence to treatment. Various strategies were developed to solve this problem. The bioconjugation between natural compounds with antimicrobial activity and cell-penetrating peptides could alleviate the resistance and toxicity of current treatments. This work aims to conjugate the cell penetration peptide TAT to the guanidine GVL1. The GVL1-TAT bioconjugate exhibited leishmanicidal activity against Leishmania amazonensis and Leishmania infantum with a high selectivity index. In addition, the bioconjugate was more active against the intracellular enzyme CPP than the individual compounds. This target is very important for the viability and virulence of the parasite within the host cell. Docking studies confirmed the higher interaction of the conjugate with CPP and suggested that other proteins, such as trypanothione reductase, could be targeted. Thus, the data indicated that guanidines conjugated with cell-penetrating peptides could be a good approach for developing antileishmanial molecules.
Hydrolysis Reactions of p-Nitrophenyl Trifluoroacetate and S-Ethyl Trifluorothioacetate
Authors: Suggs Jack B. , Melko Joshua J.
Published: January 2025

The formation of water structures can provide significant benefits in organic reactions, stabilizing charge and lowering activation energies. Hydrolysis reactions will frequently rely on water networks to accomplish these goals. Here, we used computational chemistry and experimental kinetics to investigate a model thioester molecule S-ethyl trifluorothioacetate, and extended work on a previously characterized ester p-nitrophenyl trifluoroacetate. We found that the rate-determining steps in these reactions are heavily influenced by the nature of the leaving group. The hydrolysis of S-ethyl trifluorothioacetate was much slower than p-nitrophenyl trifluoroacetate for this reason. We explored differences in the reaction orders with respect to water and examined details of calculated potential energy surfaces of these hydrolysis reactions, highlighting the roles of solvation effects and transition state structures.
MCF-DTI: Multi-Scale Convolutional Local–Global Feature Fusion for Drug–Target Interaction Prediction
Authors: Wang Jihong , He Ruijia , Wang Xiaodan , Li Hongjian , Lu Yulei
Published: January 2025

Predicting drug–target interactions (DTIs) is a crucial step in the development of new drugs and drug repurposing. In this paper, we propose a novel drug–target prediction model called MCF-DTI. The model utilizes the SMILES representation of drugs and the sequence features of targets, employing a multi-scale convolutional neural network (MSCNN) with parallel shared-weight modules to extract features from the drug side. For the target side, it combines MSCNN with Transformer modules to capture both local and global features effectively. The extracted features are then weighted and fused, enabling comprehensive feature representation to enhance the predictive power of the model. Experimental results on the Davis dataset demonstrate that MCF-DTI achieves an AUC of 0.9746 and an AUPR of 0.9542, outperforming other state-of-the-art models. Our case study demonstrates that our model effectively validated several known drug–target relationships in lung cancer and predicted the therapeutic potential of certain preclinical compounds in treating lung cancer. These findings contribute valuable insights for subsequent drug repurposing efforts and novel drug development.
Green Synthesis of Antibacterial CuO Nanoparticles Based on the Synergy Between Cornu aspersum Snail Mucus and Ascorbic Acid
Authors: Todorova Maria , Kosateva Angelina , Petrova Ventsislava , Ranguelov Bogdan , Atanasova-Vladimirova Stela , Avdeev Georgi , Stoycheva Ivanka , Pisareva Emiliya , Tomova Anna , Velkova Lyudmila , Dolashki Aleksandar , Dolashka Pavlina
Published: January 2025

Many biologically active compounds have been identified in the mucus of the garden snail Cornu aspersum, which are effective in the treatment of several diseases such as cancer, ulcers, wounds, etc. The incorporation of these compounds into the green synthesis of copper nanoparticles (CuONPs-Muc) was demonstrated in our previous study. Based on the synergistic effect of two reducing agents—C. aspersum snail mucus and ascorbic acid (AsA)—on CuSO4.5H2O, which also act as stabilizers of the resulting compound, a new method for the “green” synthesis of CuONPs-Muc is presented. Using two reducing agents has several advantages, such as forming spherical nanoparticles with a diameter of about 150 nm and reducing the formation time of CuONPs-Muc to 3 h. Analyses by ultraviolet–visible spectroscopy (UV-Vis) and Fourier transform infrared spectroscopy (FT-IR) show the formation of CuONPs-Muc, composed of a mixture of copper and copper oxide. This was confirmed by scanning electron microscopy combined with energy-dispersive spectroscopy (SEM/EDS) and X-ray diffraction (XRD). Another important advantage of CuONPs obtained by the new method with two reducing agents is the stronger inhibitory effect on the bacterial growth of some Gram-positive and Gram-negative bacterial strains, compared to CuONPs-Muc prepared with only one reducing agent, i.e., a fraction of mucus with an MW > 20 kDa.
Development of New Biosorbent Based on Crosslinked Chitosan Beads with High Brilliant Blue FCF Removal Efficiency
Authors: Lahgui Fatiha , Delgado Cano Beatriz , Avalos Ramirez Antonio , Heitz Michèle , Hadjar Hafida , Kaddour Samia
Published: January 2025

Effluents containing synthetic anionic dyes can pose a risk to ecosystems, and they must be treated before their release to the environment. Biosorption, a simple and effective process, may be a promising solution for treating these effluents. In this work, chitosan beads were crosslinked with epichlorohydrin to produce a highly stable and performant biosorbent to remove Brilliant Blue FCF dye. The biosorbent was characterized by determining the functional groups on its surface, as well as its elemental composition, crystallinity, and surface morphology. Crosslinking with epichlorohydrin significantly improved the biosorption capacity of chitosan beads. A maximum biosorption capacity of 600 mg/g corresponding to 99% removal efficiency was observed at pH 3.0, a biosorbent dose of 0.5 g/L, an initial dye concentration of 300 mg/L, a contact time of 10 h, and a temperature of 323 K. The biosorption of Brilliant Blue FCF dye in chitosan beads crosslinked with epichlorohydrin was well described by the Langmuir isotherm and followed an adsorption kinetic of pseudo second order. The thermodynamic parameters indicate a spontaneous biosorption process. The presence of anions such as NO3− and SO42− could interfere with the biosorption of Brilliant Blue FCF on the chitosan crosslinked beads, but Cl− did not interfere in biosorption process. Over three biosorption/desorption cycles, the biosorbent showed a removal efficiency of 97% and a desorption rate of over 98%. Chitosan is available worldwide and is a low-cost biomaterial, presenting high potential to be used as a biosorbent to treat industrial effluents containing anionic compounds, such as dyes.
Organocatalytic Packed-Bed Reactors for the Enantioselective Flow Synthesis of Quaternary Isotetronic Acids by Direct Aldol Reactions of Pyruvates
Authors: Poletti Lorenzo , De Risi Carmela , Ragno Daniele , Di Carmine Graziano , Tassoni Riccardo , Massi Alessandro , Dambruoso Paolo
Published: January 2025

The utilization of the homogeneous (S)-2-pyrrolidine-tetrazole organocatalyst (Ley catalyst) in the self-condensation of ethyl pyruvate and cross-aldol reactions of ethyl pyruvate donor with non-enolizable pyruvate acceptors, namely the sterically hindered ethyl 3-methyl-2-oxobutyrate or the highly electrophilic methyl 3,3,3-trifluoropyruvate, is described as the key enantioselective step toward the synthesis of the corresponding biologically relevant isotetronic acids featuring a quaternary carbon functionalized with ester and alkyl groups. The transition from homogeneous to heterogeneous flow conditions is also investigated, detailing the fabrication and operation of packed-bed reactors filled with a silica-supported version of the pyrrolidine-tetrazole catalyst (SBA-15 as the matrix).
Preparation of a Silicon/MXene Composite Electrode by a High-Pressure Forming Method and Its Application in Li+-Ion Storage
Authors: Liu Yonghao , Zhao Dawei , Cong Lujia , Han Yanfeng , Fu Mingdi , Wu Xiaoxin , Zhang Junkai
Published: January 2025

The main component of high-capacity silicon-based electrodes is silicon powder, which necessitates intricate processing to minimize volume growth and powder separation while guaranteeing the ideal Si content. This work uses the an situ high-pressure forming approach to create an MXene/m-Si/MXene composite electrode, where MXene refers to Ti3C2TX, and m-Si denotes two-phase mixed nano-Si particles. The sandwich shape promotes silicon’s volume growth and stops active particles from spreading. The conductive structure of Ti3C2TX MXene increases the efficiency of charge transfer while reducing internal resistance. After 100 cycles, the composite electrode’s original capacity of 1310.9 mAh g−1 at a current density of 0.5 A g−1 is maintained at 781.0 mAh g−1. These findings lay the foundation for further investigations into Si matrix composite electrodes.
Relationship Between the Gut Microbiome, Tryptophan-Derived Metabolites, and Osteoarthritis-Related Pain: A Systematic Review with Meta-Analysis
Authors: Meléndez-Oliva Erika , Martínez-Pozas Oliver , Sinatti Pierluigi , Martín Carreras-Presas Carmen , Cuenca-Zaldívar Juan Nicolás , Turroni Silvia , Sánchez Romero Eleuterio A.
Published: January 2025

Introduction: Osteoarthritis (OA) is the most prevalent form of arthritis and affects over 528 million people worldwide. Degenerative joint disease involves cartilage degradation, subchondral bone remodeling, and synovial inflammation, leading to chronic pain, stiffness, and impaired joint function. Initially regarded as a “wear and tear” condition associated with aging and mechanical stress, OA is now recognized as a multifaceted disease influenced by systemic factors such as metabolic syndrome, obesity, and chronic low-grade inflammation. Recent studies have focused on the gut-joint axis to investigate how the gut microbiome modulates inflammation and pain in OA. Materials and Methods: A systematic review was conducted following the PRISMA guidelines and was registered with PROSPERO (CRD42024556265). This review included studies involving adults with symptomatic OA and analyzed the relationship between the gut microbiome and OA-related pain. Randomized and non-randomized clinical trials, case reports, editorials, and pilot studies were excluded. Searches were performed in PubMed, Cochrane Library, and Web of Science without publication date restrictions, and filtered for “observational studies”. The study selection and data extraction were performed by two independent researchers, and the risk of bias was assessed using appropriate tools. Results: Five observational studies were included in the systematic review, and three were included in the meta-analysis. Two studies reported an association between different tryptophan metabolites and pain levels in patients with OA. Two other studies demonstrated a correlation between lipopolysaccharide levels and pain in OA. A fifth study confirmed the relationship between Streptococcus relative abundance of Streptococcus spp. and knee pain. These results were not supported by a meta-analysis, which found no significant association between the presence of pain in OA and the presence of bacilli of the genus Streptococcus or plasma markers of the tryptophan pathway. Conclusions: Current evidence indicates a potential link between gut microbiome dysbiosis and OA-related pain. However, methodological limitations preclude definitive conclusions. Further research using advanced techniques and larger cohorts is needed to validate and extend these findings and elucidate the underlying mechanisms. Targeted manipulation of the gut microbiome may be a valuable strategy for pain management in OA patients.
Nutritional Status and Nutritional Support in Patients with Gastrointestinal Diseases
Authors: Jabłońska Beata
Published: January 2025

Gastrointestinal diseases include a wide spectrum of functional and structural disorders of the alimentary system, involving hepatic, bile duct, and pancreatic diseases [...]
Phytochemical Composition and Antioxidant Activity of Manuka Honey and Ohia Lehua Honey
Authors: Morar Iulia Ioana , Pop Raluca Maria , Peitzner Erik , Ranga Floricuța , Orăsan Meda Sandra , Cecan Andra Diana , Chera Elisabeta Ioana , Bonci Teodora Irina , Usatiuc Lia Oxana , Țicolea Mădălina , But Anca Elena , Cătoi Florinela Adriana , Pârvu Alina Elena , Ghergie Mircea Constantin Dinu
Published: January 2025

Honey is abundant in bioactive compounds, which demonstrate considerable therapeutic effects, particularly on oxidative stress and inflammation. Objectives: This work sought to evaluate the antioxidant mechanisms of Manuka honey (MH) and Ohia Lehua honey (OLH), correlating them with phytochemical analyses in a rat model of experimentally induced inflammation. Methods: The identification of polyphenolic compounds in the extracts was carried out using HPLC-ESI MS. The extracts’ antioxidant activity was evaluated in vitro through DPPH, FRAP, H2O2, and NO scavenging assays, while in vivo assessments included measurements of total oxidative status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), advanced oxidation protein products (AOPP), malondialdehyde (MDA), nitric oxide (NO), and total thiols (SH). Results: The phytochemical analysis found a rich content of phenolic compounds in MH and lower quantities in OLH. In terms of in vitro activity, both MH and OLH exhibited strong DPPH radical scavenging abilities, effective NO and H2O2 scavenging capacities, and high FRAP-reducing power. In vivo, OLH proved highly effective in enhancing antioxidant capacity and lowering oxidative stress markers, showing significant increases in TAC and substantial reductions in TOS and OSI levels. Conversely, MH displayed limited and dose-dependent antioxidant activity, a considerable increase in TAC and SH, and a moderate decrease in TOS and OSI levels. Conclusions: To our knowledge, this is the first study to assess the phenolic content of OLH and to show its capacity to scavenge free radicals and reduce oxidative stress. The effectiveness of MH primarily relies on its increased antioxidant properties and depends on concentration. These results highlight the importance of investigating natural products in developing antioxidant strategies.
Risk Factors Associated with Hemoparasites in Dual-Purpose Cattle of Colombia
Authors: Murcia-Mono César A. , Falla-Tapias Sergio , Morales Cabrera Andrés F. , Navia Álvarez Laura C. , Rivera-Sánchez Leidy , Gómez Vargas Yolanda , Burgos-Paz William O.
Published: January 2025

Hemoparasitic diseases represent a significant problem with a considerable impact on tropical and subtropical areas of the world. These conditions cause economic losses associated with multi-organic failure and even the death of animals. In these areas, the hemoparasites are transmitted in an enzootic cycle when infectious cattle, such as persistently infected animals, including cows, contribute to the success of transmission. However, the factors associated with transmission have always been considered environmental issues, disregarding herd management and practices. In this sense, we conducted a cross-sectional study sampling 360 female cattle older than one year to identify infectious cattle using the PCR technique. We employed a dichotomic questionnaire for association analyses in 150 herds of the southern Andean region of Colombia. Overall prevalence with infectious cattle was 52.5% for Babesia spp., Anaplasma spp., and Trypanosoma spp., and the significant risk factors (p < 0.05) included geographic area, animal weight, purchase of cattle for fattening, disinfection of clothing after contact with neighboring animals, self-medication, separation of animals in pens, supply of mineralized salt, presence of livestock from other owners on the farm, prevention of joint trauma, documented milking routine, and sending blood samples for analysis. These practices permitted the maintenance of persistently infected animals and their movement to shed the agents to other animals in the presence of vectors. This suggests the importance of implementing comprehensive control and training measures to reduce the infectious cattle and, therefore, the profitability of dual-purpose livestock farms in the Andean region of southwestern Colombia.
Introduction of Vector-Borne Infections in Europe: Emerging and Re-Emerging Viral Pathogens with Potential Impact on One Health
Authors: Logiudice Jacopo , Alberti Maria , Ciccarone Andrea , Rossi Benedetta , Tiecco Giorgio , De Francesco Maria Antonia , Quiros-Roldan Eugenia
Published: January 2025

The rise and resurgence of vector-borne diseases (VBDs) in Europe pose an expanding public health challenge, exacerbated by climate change, globalization, and ecological disruptions. Both arthropod-borne viruses (arboviruses) transmitted by ticks such as Crimean–Congo hemorrhagic fever and arboviruses transmitted by mosquitoes like dengue, Chikungunya, Zika, and Japanese encephalitis have broadened their distribution due to rising temperatures, changes in rainfall, and increased human mobility. By emphasizing the importance of interconnected human, animal, and environmental health, integrated One Health strategies are crucial in addressing this complex issue. Europe faces increased risk due to the expanding habitats of disease-carrying organisms, the spread of new species like Aedes albopictus since 2013, and increased movement of infected individuals between countries, leading European countries to implement strategies such as enhanced surveillance systems, public awareness campaigns, and prompt outbreak response strategies. However, the lack of both targeted antiviral therapies and vaccines for many arboviruses, together with undetected or asymptomatic cases, hamper containment efforts. Therefore, it is important to have integrated strategies that combine climate modeling, disease surveillance, and public health interventions to address expected changes in disease patterns due to global changes. This review explores the spread of arboviruses in Europe, highlighting their historical context, current transmission dynamics, and their impact on public health.
Scrub Typhus and Influenza A Co-Infection: A Case Report
Authors: Yamamoto Chie , Maruyama Ayano , Munakata Jun , Matsuyama Tasuku , Furukawa Keitaro , Hamashima Ryosuke , Ogawa Motohiko , Hashimoto Yuki , Fukuda Akiko , Inaba Tohru , Nukui Yoko
Published: January 2025

Scrub typhus, caused by Orientia tsutsugamushi, is a neglected and reemerging disease that causes considerable morbidity and mortality. It now extends beyond the Tsutsugamushi Triangle, the region wherein it has traditionally been endemic. Influenza has also resurged since the infection control measures against COVID-19 were relaxed. A few cases of scrub typhus and influenza co-infection have been reported. Herein, we report the case of a 74-year-old woman with fever and upper respiratory symptoms diagnosed with influenza A and treated with oseltamivir; however, her fever persisted, and she developed respiratory failure, liver dysfunction, headache, diarrhea, and an erythematous skin rash. She lived in a forested area where scrub typhus was endemic and worked on a farm. Physical examination revealed an eschar on her posterior neck, and she was diagnosed with scrub typhus and influenza A co-infection. After minocycline treatment, her symptoms improved within a few days. This is the first reported case of scrub typhus and influenza A co-infection in Japan. This case illustrates that co-infection should be suspected in patients with fever persisting after their initial infection has been treated and that in patients living in endemic areas, scrub typhus can occur concurrently with influenza. The symptoms of scrub typhus are flu-like and nonspecific, which may delay diagnosis and treatment.
Antibiotic Resistance of Staphylococcus aureus Strains—Searching for New Antimicrobial Agents—Review
Authors: Michalik Michał , Podbielska-Kubera Adrianna , Dmowska-Koroblewska Agnieszka
Published: January 2025

Inappropriate and excessive use of antibiotics is responsible for the rapid development of antimicrobial resistance, which is associated with increased patient morbidity and mortality. There is an urgent need to explore new antibiotics or alternative antimicrobial agents. S. aureus a commensal microorganism but is also responsible for numerous infections. In addition to innate resistance to β-lactam antibiotics, S. aureus strains resistant to methicillin (MRSA) often show resistance to other classes of antibiotics (multidrug resistance). The advancement of phage therapy against MRSA infections offers a promising alternative in the context of increasing antibiotic resistance. Therapeutic phages are easier to obtain and cheaper to produce than antibiotics. However, there is still a lack of standards to ensure the safe use of phages, including purification, dosage, means of administration, and the quantity of phages used. Some bacteria have developed defense mechanisms against phages. The use of phage cocktails or the combination of antibiotics and phages is preferred. For personalized therapy, it is essential to set up large collections to enable phage selection. In the future, the fight against MRSA strains using phages should be based on a multidisciplinary approach, including molecular biology and medicine. Other therapies in the fight against MRSA strains include the use of endolysin antimicrobial peptides (including defensins and cathelicidins). Researchers’ activities also focus on the potential use of plant extracts, honey, propolis, alkaloids, and essential oils. To date, no vaccine has been approved against S. aureus strains.
Sambucus nigra-Lyophilized Fruit Extract Attenuated Acute Redox–Homeostatic Imbalance via Mutagenic and Oxidative Stress Modulation in Mice Model on Gentamicin-Induced Nephrotoxicity
Authors: Petkova-Parlapanska Kamelia , Stefanov Ivaylo , Ananiev Julian , Georgiev Tsvetelin , Hadzhibozheva Petya , Petrova-Tacheva Veselina , Kaloyanov Nikolay , Georgieva Ekaterina , Nikolova Galina , Karamalakova Yanka
Published: January 2025

Background: Gentamicin (GM) administration is associated with decreased metabolism, increased oxidative stress, and induction of nephrotoxicity. Sambucus nigra L., containing flavonoids, anthocyanins, and phytosterols, possesses antioxidant and anti-inflammatory potential. Objectives: The present study aimed to investigate the nephroprotective and anti-inflammatory potential of lyophilized Sambucus nigra fruit extract (S. nigra extract) to reduce acute oxidative stress and residual toxicity of GM in a 7-day experimental model in Balb/c rodents. Methods: The S. nigra extract was lyophilized (300 rpm; 10 min; −45 °C) to improve pharmacological properties. Balb/c mice were divided into four (n = 6) groups: controls; S. nigra extract per os (120 mg kg−1 day−1 bw); GM (200 mg kg−1 day−1 bw) (4); and GM + S. nigra therapy. The activities of antioxidant and renal enzymes, cytokines, and levels of oxidative stress biomarkers—Hydroxiproline, CysC, GST, KIM-1, PGC-1α, MDA, GSPx—were analyzed by ELISA tests. The ROS and RNS levels, as well as 5-MSL-protein oxidation, were measured by EPR spectroscopy. Results: The antioxidant-protective effect of S. nigra extract (120 mg kg−1) was demonstrated by reduced MDA, ROS, and RNS and increased activation of endogenous enzymes. Furthermore, S. nigra extract significantly reduced the expression of IL-1β, IL-6, IL-10, TNF-α, IFN-γ, and KIM-1 and regulated collagen/protein (PGC-1α and albumin) deposition in renal tissues. Conclusions: Histological evaluation confirmed that S. nigra (120 mg kg−1) attenuated renal dysfunction and structural damage by modulating oxidative stress and acute inflammation and could be used as an anti-fibrotic alternative in GM nephrotoxicity.
Nanoformulation of Spirooxindole and Methods for Treating Hepatocellular Carcinoma
Authors: Barakat Assem , El-Senduny Fardous F. , Islam Mohammad Shahidul , Al-Majid Abdullah Mohammed , Elshaier Yaseen A. M. M. , Mazyed Eman A. , Badria Farid A.
Published: January 2025

Objectives: This in vivo study introduces a newly developed spirooxindole derivative that is deemed safe and effective as a potential targeted therapy for various cancers. Methods: Extensive in vivo investigations, including histopathology, immunohistochemistry, and molecular biology, validated its potential for further preclinical and clinical exploration, necessitating comprehensive examinations of its bioavailability, pharmacodynamics, and pharmacokinetics. Additionally, this study involves the development of a commercially viable proniosomal drug delivery system for the compound, facilitating controlled drug release. Results: The data revealed efficacy of spirooxindole derivative in halting the progression of liver cancer, metastasis, and portal vein thrombosis, with potential implications for enhancing regeneration and recovery of early-stage cancer cells in multiple organs, thereby improving recovery rates and remission among cancer patients. The proniosomes, loaded with the compound, exhibited high entrapment efficiency and prolonged drug release rates of up to 12 h in vitro. The optimized formula demonstrated superior drug release percentages and stability compared to conventional niosomes. Further analysis via FTIR and DSC confirmed the absence of chemical interactions and proper entrapment of the compound within the nanovesicles, indicating a stable and effective drug delivery system. Conclusions: This study presents a novel, safe, and effective chemical entity of spirooxindole derivatives for further preclinical and clinical studies.
Rab21-Targeted Nano Drug Delivery System-Based FFPG for Efficient Paclitaxel Delivery to Inhibit Lung Cancer Progression
Authors: Wang Jing , Yan Xueying , Wang Wenfei , Wang Shu , Jiang Hongxiang , Zhu Xinhua , Li Zhehui , Cai Defu , Xia Yonggang
Published: January 2025

Background/Objectives: Platycodon grandiflorus (PG) has been widely researched as a conductant drug for the treatment of lung diseases by ancient and modern traditional Chinese medicine (TCM) practitioners. Inspired by the mechanism and our previous finding about fructans and fructooligosaccharides from Platycodon grandiflorus (FFPG), we developed a nano drug delivery system (NDDS) targeting lung cancer. The aim was to improve the efficiency of the liposomal delivery of Paclitaxel (PTX) and enhance the anti-tumor efficacy. Methods: The FFPG-Lip-PTX NDDS was prepared by electrostatic adsorption. Dynamic light scattering, zeta potential, and transmission electron microscopy were used for physical characterization. The release behavior of the NDDS was simulated by dialysis. The uptake of the NDDS was observed by confocal microscopy and flow cytometry. Cytotoxicity, apoptosis, migration, and invasion experiments were used to evaluate the anti-tumor ability of the NDDS in vitro. The penetration and inhibition of tumor proliferation were further analyzed via a 3D tumor sphere model. Finally, in vivo biological distribution and pharmacodynamic experiments verified the targeting and anti-tumor ability of the FFPG-Lip-PTX NDDS. Results: FFPG-Lip-PTX possessed a homogeneous particle size distribution, high encapsulation efficiency, and stability. In vitro experiments confirmed that FFPG promoted the uptake of the NNDS by tumor cells and enhanced cytotoxicity. It also increased the anti-tumor effect by promoting cell apoptosis and inhibiting invasion and metastasis. The same conclusion was obtained in 3D tumor spheres. In vivo experiments exhibited that FFPG-lips-PTX showed more significant lung cancer-targeting activity and anti-tumor effects. Conclusions: In this study, a novel lung-targeted NDDS is proposed to enhance the therapeutic effect of chemotherapy drugs on lung cancer.
Integration of Metabolomics and Transcriptomics to Reveal the Antitumor Mechanism of Dendrobium officinale Polysaccharide-Based Nanocarriers in Enhancing Photodynamic Immunotherapy in Colorectal Cancer
Authors: Tao Shengchang , Wang Huan , Ji Qiufeng , Yang Yushan , Wei Gang , Li Ruiming , Zhou Benjie
Published: January 2025

Background: The mechanism of Dendrobium officinale polysaccharide-based nanocarriers in enhancing photodynamic immunotherapy in colorectal cancer (CRC) remains poorly understood. Methods: The effects of TPA-3BCP-loaded cholesteryl hemisuccinate–Dendrobium officinale polysaccharide nanoparticles (DOP@3BCP NPs) and their potential molecular mechanism of action in a tumor-bearing mouse model of CRC were investigated using non-targeted metabolomics and transcriptomics. Meanwhile, a histopathological analysis (H&E staining, Ki67 staining, and TUNEL assay) and a qRT-PCR analysis revealed the antitumor effects of DOP@3BCP NPs with and without light activation. Results: Through metabolomics and transcriptomics analysis, we found an alteration in the metabolome and functional pathways in the examined tumor tissues. The metabolic analysis showed 69 and 60 differentially expressed metabolites (DEMs) in positive- and negative-ion modes, respectively, in the treated samples compared to the Control samples. The transcriptomics analysis showed that 1352 genes were differentially expressed among the three groups. The differentially regulated functional pathways were primally related to the antitumor immune response. The results of the pathological histology assay and qRT-PCR analysis verified the findings of the integrated metabolomics and transcriptomics analysis. Conclusions: Overall, our findings elucidate the potential antitumor mechanisms of the D. officinale polysaccharide-based nanocarrier in enhancing photodynamic immunotherapy in CRC.
Visual Acuity Outcomes and Influencing Factors in a Cohort of UK Real-World Diabetic Macular Oedema Patients During the First Two Years of Anti-VEGF Treatment
Authors: Wen Qing , Karcher Helene , Wright David M. , Sinha Samriddhi Buxy , Chakravarthy Usha , Santos Catarina , Igwe Franklin , Salongcay Recivall , Curran Katie , Peto Tunde
Published: January 2025

Background/Objectives: The visual acuity (VA) outcomes after the first and second years of anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with diabetic macular oedema (DMO) were evaluated, and the factors associated with treatment success were investigated. Methods: Using Medisoft electronic medical records (UK), this retrospective cohort study analysed VA outcomes, changes, and determinants in DMO patients at year 1 and year 2 after initial anti-VEGF injection. Descriptive analysis examined baseline demographics and clinical characteristics, while regression models were used to assess associations between these factors and changes in VA. Results: 728 DMO patients (1035 eyes) treated with anti-VEGFs (ranibizumab, aflibercept, or bevacizumab) at the Northern Ireland Mater Macular Clinic from 2008 to 2021 were evaluated. The mean age was 64.5 (SD 12.8) years, and 59.6% were male. In the first year, the median annual injection number and interval were 6.0 (IQR 5.0–8.0) and 6.1 weeks (IQR 5.4–7.8), respectively, and in the second year, they were 3.0 (IQR 2.0–5.0) and 10.0 weeks (IQR 6.5–20.1). In the first two treatment years, 83.4% and 79.8% of eyes had improved/stable VA (ISVA) respectively. The injection number, interval, baseline VA, age, and proliferative diabetic retinopathy (PDR) significantly impacted VA outcomes. Conclusions: Our study confirms the effectiveness of anti-VEGF treatments in improving or maintaining vision for DMO patients, consistent with previous real-world clinical data. An elder age, a better baseline VA, low annual injection numbers (<5), and less frequent injection intervals (≥12 weeks) were negatively associated with ISVA success in the first two years. These findings have implications for managing patient expectations, allocating resources, and understanding DMO clinical management.
[99mTc]Technetium and Rhenium Dithiocarbazate Complexes: Chemical Synthesis and Biological Assessment
Authors: de Araujo Fernandes André Gustavo , Lafratta Alyne Eloise , Luz Carolina Portela , Levy Debora , de Paula Faria Daniele , Buchpiguel Carlos Alberto , Abram Ulrich , Deflon Victor Marcelo , Navarro Marques Fabio Luiz
Published: January 2025

Background/Objectives: Dithiocarbazates (DTCs) and their metal complexes have been studied regarding their property as anticancer activities. In this work, using S-benzyl-5-hydroxy-3-methyl-5-phenyl-4,5-dihydro-1H-pirazol-1-carbodithionate (H2bdtc), we prepared [ReO(bdtc)(Hbdtc)] and [[99mTc]TcO(bdtc)(Hbdtc)] complexes for tumor uptake and animal biodistribution studies. Methods: Re complex was prepared by a reaction of H2bdtc and (NBu4)[ReOCl4], the final product was characterized by IR, 1H NMR, CHN, and MS-ESI. 99mTc complex was prepared by the reaction of H2bdtc and [[99mTc]TcO4− and analyzed by planar and HPLC radiochromatography, and the stability was evaluated against amino acids and plasma. Biodistribution was performed in C57B/6 mice with B16F10 and TM1M implanted tumor. Results: Re is asymmetric coordinated by two dithiocarbazate ligands, one with O,N,S chelation, and the other with N,S chelation; [[99mTc]TcO(bdtc)(Hbdtc)] was prepared with a radiochemical yield of around 93%. The radioactive complex is hydrophobic (LogP = 1.03), stable for 6 h in PBS and L-histidine solution; stable for 1 h in plasma, but unstable in the presence of L-cysteine. Ex vivo biodistribution demonstrated that the compound has a fast and persistent (until 2 h) uptake by the spleen (55.46%), and tumor B16F10 and TM1M uptake is lower than 1%. In vivo SPECT/CT imaging confirmed ex vivo biodistribution, except by heterogenous TM1M accumulation but not in the B16-F10 lineage. Conclusions: H2bdtc proved to be an interesting chelator for rhenium or [99mTc]technetium. The right spleen uptake opened the opportunity to deepen the study of the molecule in this tissue and justifies future studies to identify the reason of heterogenous uptake in TM1M tumor uptake.
Snapshot Imaging of Stokes Vector Polarization Speckle in Turbid Optical Phantoms and In Vivo Tissues
Authors: Louie Daniel C. , Kulcsar Carla , Contreras-Sánchez Héctor A. , Zabel W. Jeffrey , Lee Tim K. , Vitkin Alex
Published: January 2025

Significance: We present a system to measure and analyze the complete polarization state distribution of speckle patterns generated from in vivo tissue. Accurate measurement of polarization speckle requires both precise spatial registration and rapid polarization state acquisition. A unique measurement system must be designed to achieve accurate images of polarization speckle patterns for detailed investigation of the scattering properties of biological tissues in vivo. Aim and approach: This system features a polarization state analyzer with no moving parts. Two pixel-polarizer cameras allow for the instantaneous acquisition of the spatial Stokes vector distribution of polarization speckle patterns. System design and calibration methods are presented, and representative images from measurements on liquid phantoms (microsphere suspensions) and in vivo healthy and tumor murine models are demonstrated and discussed. Results and Conclusions: Quantitative measurements of polarization speckle from microsphere suspensions with controlled scattering coefficients demonstrate differences in speckle contrast, speckle size, and the degree of polarization. Measurements on in vivo murine skin and xenograft tumor tissue demonstrate the ability of the system to acquire snapshot polarization speckle images in living systems. The developed system can thus rapidly and accurately acquire polarization speckle images from different media in dynamic conditions such as in vivo tissue. This capability opens the potential for future detailed investigation of polarization speckle for in vivo biomedical applications.
Design, Analysis, and Implementation of the Subdivision Interpolation Technique for the Grating Interferometric Micro-Displacement Sensor
Authors: Tang Jiuhui , Peng Haifeng , Yang Peng , Guo Shangzhou , Sun Wenqiang , Jin Li , Xie Kunyang , Li Mengwei
Published: January 2025

A high-resolution grating interferometric micro-displacement sensor utilizing the subdivision interpolation technique is proposed and experimentally demonstrated. As the interference laser intensity varies sinusoidally with displacement, subdivision interpolation is a promising technique to achieve micro-displacement detection with a high resolution and linearity. However, interpolation errors occur due to the phase imbalance, offset error, and amplitude mismatch between the orthogonal signals. To address these issues, a subdivision interpolation circuit, along with 90-degree phase-shifter and high-precision DC bias-voltage techniques, converts an analog sinusoidal signal into standard incremental digital signals. This novel methodology ensures that its performance is least affected by the nonidealities induced by fabrication and assembly errors. Detailed design, analysis, and experimentation studies have been conducted to validate the proposed methodology. The experimental results demonstrate that the micro-displacement sensor based on grating interferometry achieved a displacement resolution of less than 1.9 nm, an accuracy of 99.8%, and a subdivision interpolation factor of 208. This research provides a significant guide for achieving high-precision grating interferometric displacement measurements.
Modeling Femtosecond Beam Propagation in Dielectric Hollow-Core Waveguides
Authors: Tosa Valer , Gherman Ana Maria Mihaela , Kovacs Katalin , Tóth István
Published: January 2025

The propagation of femtosecond pulses in guided structures is a matter of both fundamental and practical interest in nonlinear optics. In particular, hollow-core waveguides (HCWs) filled with a gas medium are fabricated and used as devices for the generation of attosecond pulses from high-order harmonics. In this process, the configuration of the laser field (intensity and phase) inside the waveguide is of crucial importance for enhancing the (well-known, low) efficiency of high-order harmonic generation (HHG). Here, we present numerical calculations which demonstrate the main features of the propagation process in fabricated HCWs. We consider a variety of experimental parameters like gas pressure, waveguide size, laser wavelength, and pulse energy and duration. In particular, the beam profile at the fiber input is found to be a sensitive parameter which influences the whole evolution of the laser field along the propagation. Our model is based on a split-step method modified to account for propagation in ionized media and is validated against experimental and theoretical data from the literature. Our results contribute to the description of the main features of beam propagation in HCWs and provide guiding directions for designing efficient configurations for HHG.
Defining Running Intensity Domains from Critical Speed Derived from a 3-Minute All-Out Running Test
Authors: Tsai Ming-Chang , Lee Leanna S. , Thomas Scott
Published: January 2025

Background/Objectives: This study examines the utility of the 3-min all-out test (3MT) in determining exercise intensity domains through critical speed (CS), offering a practical alternative to traditional VO2max-based methods. Methods: Eighteen trained runners completed both the 3MT and a graded treadmill test. CS, VO2max, and HRmax were measured and compared to markers such as ventilation threshold (VT), gas exchange threshold (GET), lactate threshold (LT), onset of blood lactate accumulation (OBLA), CS, and VO2max, which are threshold markers for defining six exercise intensity domains. Results: Results demonstrate that CS reliably distinguishes among six exercise intensity domains with greater precision and less variability than heart rate (HR) or VO2-derived metrics. Notably, HR was unable to differentiate between high-intensity domains, highlighting its limitations for performance prescription. Compared to VO2max testing, the 3MT offers a simpler, non-invasive, and time-efficient approach to identifying training zones and monitoring performance. CS effectively delineated moderate-to-heavy, heavy-to-severe, and severe-to-extreme intensity domains, with strong correlations to performance thresholds. The findings emphasize the accessibility and reliability of the 3MT, particularly in overcoming the logistical challenges of traditional testing methods. Conclusions: This research underscores the potential of the running 3MT as a valuable tool for individualized training prescription and performance monitoring in both research and applied sports contexts, paving the way for a broader adoption in athletic training methodologies.
Genome- and Transcriptome-Wide Characterization and Expression Analyses of bHLH Transcription Factor Family Reveal Their Relevance to Salt Stress Response in Tomato
Authors: Zhang Jianling , Liu Xiaoying , Yin Zuozhen , Zhao Tiantian , Du Dan , Li Jing , Zhu Mingku , Sun Yueying , Pan Yu
Published: January 2025

The bHLH (basic helix–loop–helix) transcription factors function as crucial regulators in numerous biological processes including abiotic stress responses and plant development. According to our RNA-seq analysis of tomato seedlings under salt stress, we found that, although the bHLH gene family in tomato has been studied, there are still so many tomato bHLH genes that have not been identified and named, which will hinder the later study of SlbHLHs. In total, 195 SlbHLHs that were unevenly distributed onto 12 chromosomes were identified from the tomato genome and were classified into 27 subfamilies based on their molecular features. The collinearity between SlbHLHs and interrelated orthologs from 10 plants further revealed evolutionary insights into SlbHLHs. Cis-element investigations of SlbHLHs promotors further suggested the potential roles of SlbHLHs in tomato development and stress responses. A total of 30 SlbHLHs were defined as the differentially expressed genes in response to salt stress by RNA-seq. The expression profiles of selected SlbHLHs were varyingly and markedly induced by multiple abiotic stresses and hormone treatments. These results provide valuable information to further understand the significance and intricacy of the bHLH transcription factor family, and lay a foundation for further exploring functions and possible regulatory mechanisms of SlbHLH members in abiotic stress tolerance, which will be significant for the study of tomato stress resistance and agricultural productivity.