bluuebunny/crossref_metadata_2025 huggingface dataset:
Ozone/Thiosulfate-Assisted Leaching of Cu and Au from Old Flotation Tailings
Authors: Trujić Stefan , Popović Miroslav P. , Conić Vesna , Janošević Miloš , Alimpić Filip , Bajić Dragoljub , Milenković-Anđelković Ana , Abramović Filip
Published: January 2025

The growing demand for metal production promotes the search for alternative sources and novel modalities in metallurgy. Flotation tailings are an important secondary mineral resource; however, they might pose a potential environmental threat due to containing toxic metals. Therefore, proper leaching reagent selection is required. Ozone is an alternative oxidizing agent for metal leaching, as its use prevents contaminating product generation while increasing the noble metal extraction efficiency in the presence of complexing agents. In this study, the feasibility and efficiency of combining the use of thiosulfate and ozone for gold and silver extraction have been investigated as an eco-friendly alternative for recovery from flotation tailings. Two sets of samples from old flotation tailings of Copper Mine Bor (Serbia) were prepared and physico-chemically characterized, then treated in two experimental leaching procedures, followed by thorough XRD and SEM/EDS analyses of the products. It showed that after 1 h of leaching in a water medium at room temperature and a solid-to-liquid phase ratio of 1:4, 88.8% of Cu was obtained, while a high efficiency of Au extraction from solid residue (after Cu leaching) was attained (83.4%). The results suggest that ozone-assisted leaching mediated by Ca-thiosulfate can be an effective eco-friendly treatment for noble metals recovery from sulfide-oxide ores.
The Diverse Binding Modes Explain the Nanomolar Levels of Inhibitory Activities Against 1-Deoxy-d-Xylulose 5-Phosphate Reductoisomerase from Plasmodium falciparum Exhibited by Reverse Hydroxamate Analogs of Fosmidomycin with Varying N-Substituents
Authors: Takada Sana , Abdullaziz Mona A. , Höfmann Stefan , Knak Talea , Ozawa Shin-ichiro , Sakamoto Yasumitsu , Kurz Thomas , Tanaka Nobutada
Published: January 2025

It is established that reverse hydroxamate analogs of fosmidomycin inhibit the growth of Plasmodium falciparum by inhibiting 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), the second enzyme of the non-mevalonate pathway, which is absent in humans. Recent biochemical studies have demonstrated that novel reverse fosmidomycin analogs with phenylalkyl substituents at the hydroxamate nitrogen exhibit inhibitory activities against PfDXR at the nanomolar level. Moreover, crystallographic analyses have revealed that the phenyl moiety of the N-phenylpropyl substituent is accommodated in a previously unidentified subpocket within the active site of PfDXR. In this study, the crystal structures of PfDXR in complex with a series of reverse N-phenylalkyl derivatives of fosmidomycin were determined to ascertain whether the high inhibitory activities of the derivatives are consistently attributable to the utilization of the subpocket of PfDXR. While all reverse fosmidomycin derivatives with an N-substituted phenylalkyl group exhibit potent inhibitory activity against PfDXR, the present crystal structure analyses revealed that their binding modes to the PfDXR are not uniform. In these compounds, the nanomolar inhibitory activities appear to be driven by binding modes distinct from that observed for the inhibitor containing the N-phenylpropyl group. The structural information obtained in this study will provide a basis for further design of fosmidomycin derivatives.
Impact of Polysorbate 80 on the Antimicrobial Activity of Oregano and Thyme
Authors: Carvalho Marta , Barbosa Joana , da Silva Marcelo Belchior Rosendo , Albano Helena , Teixeira Paula
Published: January 2025

Plant-derived essential oils (EOs) possess significant antimicrobial potential against spoilage and pathogenic microorganisms. However, their efficacy can vary depending on the test method, making it difficult to standardise results. This study aimed to investigate the effect of polysorbate 80, a common surfactant used to emulsify EOs, on antimicrobial activity and minimum inhibitory concentration (MIC) determinations. The antimicrobial activity of oregano and thyme EOs was tested against 40 microorganisms with and without the presence of polysorbate 80. Antimicrobial activity was qualitatively assessed using the disc diffusion assay (DDA) and quantitatively via broth microdilution to determine MIC values. Both oregano and thyme EOs exhibited antimicrobial activity against all tested microorganisms in the DDA, regardless of the surfactant’s presence. However, MIC determinations revealed that higher EO concentrations were required to inhibit microbial growth when polysorbate 80 was included in the emulsification process. These findings indicate that polysorbate 80 influences antimicrobial test results by reducing EO efficacy while enhancing solution homogeneity and handling in aqueous media. The study highlights the critical role of emulsifiers in antimicrobial testing, as their use can significantly impact the interpretation of results and the perceived effectiveness of EOs in food preservation, pharmaceuticals, and other applications.
Equilibrium Adsorption of Organic Compounds (Nitrobenzene Derivative, Synthetic Pesticide, Dye, and Surfactant) on Activated Carbon from Single- and Multi-Component Systems
Authors: Blachnio Magdalena , Zienkiewicz-Strzalka Malgorzata , Derylo-Marczewska Anna
Published: January 2025

This work aimed to investigate the adsorption of organic compounds (4-nitroaniline and 4-chlorophenoxyacetic acid) on activated carbon in the presence of selected dyes (uranine and Acid Red 88) and surfactants (sodium dodecyl sulfate and hexadecyltrimethylammonium bromide). The adsorbent, i.e., the activated carbon RIAA (experimental activated carbon, Norit NV, Amersfoort, The Netherlands), was fully characterised by nitrogen adsorption/desorption isotherms, potentiometric titration, small-angle X-ray scattering, X-ray photoelectron spectroscopy, and transmission electron microscopy. The measurements of the adsorption isotherms of individual adsorbates from aqueous solutions were performed, and the Generalised Freundlich equation (GF) was used for their analysis. The influence of the properties of the co-adsorbates and the adsorbent on the efficiency of removal of 4-nitroaniline and 4-chlorophenoxyacetic acid from the water phase was discussed. A sieving effect was found—large dye and surfactant molecules do not penetrate the micropores but only locate at their entrances, limiting the availability of carbon adsorption space for the nitro compound and the pesticide. A very clear influence of the co-adsorbates’ concentration on the adsorption efficiency of the organic pollutants from the mixture was also observed. When the CMC (critical micelle concentration) value was exceeded in the system with surfactant as the co-adsorbent, a decrease in the competition effect on the adsorption of 4-chlorophenoxyacetic acid was observed. This is due to the formation of large aggregates of the surfactant in the solution, which are poorly adsorbed on the activated carbon.
Are We Ready to Measure Skin Permeation of Modern Antiaging GHK–Cu Tripeptide Encapsulated in Liposomes?
Authors: Ogórek Karolina , Nowak Kinga , Wadych Emilia , Ruzik Lena , Timerbaev Andrei R. , Matczuk Magdalena
Published: January 2025

Cosmetically active compounds (CACs), both of lipophilic and hydrophilic origin, have difficulty reaching the deeper layers of the skin, and this shortcoming significantly reduces their efficacy. One such CAC that occurs naturally in the human body and displays many beneficial properties (via reducing fine lines and wrinkles, tightening skin, improving its elasticity, etc.) is the glycyl-L-histidyl-L-lysine tripeptide complex of copper (GHK–Cu). GHK–Cu is a fairly hydrophilic compound with limited permeation through the lipophilic stratum corneum. On the other hand, liposomes capable of encapsulating GHK–Cu may improve its permeation potential. The present review discusses various issues related to obtaining insight into the permeation of CACs through the skin. Methods for studying the transport of CACs encapsulated by liposomes and free GHK–Cu across the skin barrier are summarized. An analysis of the literature data reveals that the transport of liposomes containing GHK–Cu received little attention. This research gap gives an impetus to the methodological developments for assessing the effect of liposomes on GHK–Cu transportation and trafficking.
Laser Desorption-Ion Mobility Spectrometry of Explosives for Forensic and Security Applications
Authors: Felizzato Giorgio , Sabo Martin , Petrìk Matej , Romolo Francesco Saverio
Published: January 2025

Background: The detection of explosives in crime scene investigations is critical for forensic science. This study explores the application of laser desorption (LD) ion mobility spectrometry (IMS) as a novel method for this purpose utilising a new IMS prototype developed by MaSaTECH. Methods: The LD sampling technique employs a laser diode module to vaporise explosive traces on surfaces, allowing immediate analysis by IMS without sample preparation. Chemometric approaches, including multivariate data analysis, were utilised for data processing and interpretation, including pre-processing of raw IMS plasmagrams and various pattern recognition techniques, such as linear discriminant analysis (LDA) and support vector machines (SVMs). Results: The IMS prototype was validated through experiments with pure explosives (TNT, RDX, PETN) and explosive products (SEMTEX 1A, C4) on different materials. The study found that the pre-processing method significantly impacts classification accuracy, with the PCA-LDA model demonstrating the best performance for real-world applications. Conclusions: The LD-IMS prototype, coupled with effective chemometric techniques, presents a promising methodology for the detection of explosives in forensic investigations, enhancing the reliability of field applications.
Effect of Beetroot Juice Supplementation on Aerobic Capacity in Female Athletes: A Randomized Controlled Study
Authors: Neteca Jekaterina , Veseta Una , Liepina Inga , Volgemute Katrina , Dzintare Maija , Babarykin Dmitry
Published: January 2025

Background/Objectives: This study addresses the growing interest in nutritional supplements that improve athletic performance in endurance sports. Previous research suggests that nitrates in beetroot juice enhance blood vessel dilation and oxygen delivery to muscles. However, the effects of these nitrates on cardiopulmonary performance in female athletes remain underexplored. The aim of this study was to evaluate the effect of beetroot juice supplementation on aerobic work capacity in female endurance athletes. Methods: A cardiopulmonary exercise test (CPET) was conducted to assess aerobic work capacity. Eighteen healthy female endurance athletes (22.9 ± 5.6 years) participated in the study. The participants were randomly assigned to two groups: the control group (placebo group n = 9), which received a nitrate-free placebo beverage, and the experimental group (beetroot juice group n = 9), which consumed 50 mL of beetroot juice concentrate (~6.2 mmol nitrate) two and a half hours before the second test. Results: The results showed that the beetroot juice group demonstrated significant improvements in minute ventilation (VE), respiratory equivalents (VE/VO2 and VE/VCO2), and heart rate (HR) (p < 0.05). Maximal oxygen consumption (VO2 max) increased by 4.82% in the beetroot juice group (from 35.24 ± 5.07 to 36.94 ± 4.91 mL·min−1·kg−1), whereas a small decrease was observed in the placebo group. Conclusions: These findings indicate that beetroot juice may be an effective ergogenic aid, enhancing oxygen utilization and energy production during exercise in female athletes. In terms of practical applications, beetroot juice could contribute to improved athletic performance and serve as a valuable addition to athletes’ nutritional plans. Future studies should explore the long-term effects, optimal dosages, and duration of supplementation in larger and more diverse populations.
Understanding Consumers to Enhance Demand for Sustainable Diets: Comment on “Adopting Sustainable Dietary Patterns: Effects of Food Labeling, Food Choices, and Eating Behaviors”
Authors: Marinangeli Christopher P. F.
Published: January 2025

The creation of sustainable food systems is a “wicked problem”; it is multifaceted with no single or one-size-fits-all solution [...]
The Potential Mechanism of Alpiniae oxyphyllae Fructus Against Hyperuricemia: An Integration of Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro Experiments
Authors: Zhang Shuanggou , Yang Yuanfei , Zhang Ruohan , Gao Jian , Wu Mengyun , Wang Jing , Sheng Jun , Sun Peiyuan
Published: January 2025

Background: Alpiniae oxyphyllae Fructus (AOF) is a medicinal and edible resource that holds potential to ameliorate hyperuricemia (HUA), yet its mechanism of action warrants further investigation. Methods: We performed network pharmacology, molecular docking, molecular dynamics simulation, and in vitro experiments to investigate the potential action and mechanism of AOF against HUA. Results: The results indicate that 48 potential anti-HUA targets for 4 components derived from AOF were excavated and predicted through public databases. Gene Ontology (GO) enrichment analysis indicated that there are 190 entries related to biological process, 24 entries related to cellular component, 42 entries related to molecular function, and 44 entries related to Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. The results of molecular docking showed that the main active ingredients of AOF may have potential therapeutic effects on immune system disorders and inflammation caused by HUA by binding to targets including peroxisome-proliferator-activated receptor gamma (PPARG), estrogen receptor 1 (ESR1), prostaglandin G/H synthase 2 (PTGS2), and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Subsequently, we further determined the stability of the complex between the core active ingredient and the core target proteins by molecular dynamics simulation. The results of cell experiments demonstrated that stigmasterol as the core active ingredient derived from AOF significantly upregulated the expression levels of ESR1 and PPARG (p < 0.001) to exert an anti-HUA effect. Conclusions: In summary, we have systematically elucidated that the mechanism of main active ingredients derived from AOF mainly exert their pharmacological effects by acting on multiple targets in this study. Our studies will provide a scientific basis for the precise development and utilization of AOF.
Effect of Proanthocyanidins from Grape Seed Extract on Benign Prostatic Hyperplasia
Authors: Iannuzzo Fortuna , Schiano Elisabetta , Maisto Maria , Schettino Anna , Marigliano Noemi , Saviano Anella , Abo Mansour Adel , Iqbal Asif Jilani , Maione Francesco , Tenore Gian Carlo , Novellino Ettore
Published: January 2025

Background/Objectives: Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases affecting the urinary tract that occurs mainly in men over 40 years of age. Among the natural therapies, proanthocyanidins (PACs), which can treat a wide range of immune-mediated inflammatory diseases (IMIDs), have been shown to play an important role in the treatment of pathologies concerning prostate health. In this regard, the present study aimed to evaluate the different bioactivities of a grape seed extract (GSE), rich in polymeric PACs, and its version processed under alkaline conditions (ATGSE), characterized by a higher content of oligomeric PACs, in an animal model of BPH induced by subcutaneous injection of testosterone (1 mg/mouse). Methods: These latter were divided into a control group (vehicle, olive oil), a BPH group (testosterone 1 mg/mouse), and four treatment groups treated with GSE (500 mg/kg) and ATGSE (125, 250, 500 mg/kg) by oral gavage. At the experimental endpoint (4 weeks), hematological and biochemical analyses of blood and tissues were performed. Results: Data showed that oral administration of ATGSE (250 mg/kg) was significantly more effective than GSE in reducing prostate (p ≤ 0.0001) and seminal vesicle (p ≤ 0.0001) weight. Moreover, ATGSE exhibited enhanced effectiveness in significantly reducing PSA levels (p ≤ 0.0001 vs. GSE) and the expression of key pro-inflammatory cyto-chemokines in prostate and seminal vesicles homogenates. Conclusions: These findings pave the way for the clinical application of ATGSE as a nutraceutical and/or functional food.
Plasma Bacterial Metabolites in Crohn’s Disease Pathogenesis and Complications
Authors: Deskur Anna , Ambrożkiewicz Filip , Samborowska Emilia , Błogowski Wojciech , Sulikowski Tadeusz , Białek Andrzej , Zawada Iwona , Dąbkowski Krzysztof , Mitrus Joanna , Karczmarski Jakub , Cybula Patrycja , Paziewska Agnieszka , Starzyńska Teresa
Published: January 2025

Background/Objectives: Crohn’s disease is known for being associated with an abnormal composition of the bacterial flora, dysbiosis and intestinal function disorders. Metabolites produced by gut microbiota play a pivotal role in the pathogenesis of CD, and the presence of unspecific extraintestinal manifestations. Methods: The aim of this study was a determination of the level of bacterial metabolites in blood plasma in patients with Crohn’s disease. CD patients (29) and healthy individuals (30) were recruited for this study. Bacterial metabolites (SCFAs and TMAO panel) were measured by a liquid chromatography–mass spectrometry system. Results: A significant correlation (p-value < 0.05) between CD and bacterial metabolites was obtained for three of eight tested SCFAs; acetic acid (reduced in CD; FC 1.7; AUC = 0.714), butyric acid (increased; FC 0.68; AUC = 0.717), 2MeBA (FC 1.168; AUC = 0.702), and indoxyl (FC 0.624). The concentration of CA (FC 0.82) and choline (FC 0.78) in plasma was significantly disturbed according to the biological treatment. Choline level (FC 1.28) was also significantly disturbed in the patients treated with glucocorticoids. In total, 68.97% of Crohn’s patients presented extraintestinal manifestations (EIMs) of Crohn’s disease, mainly osteoarticular complications. The level of BA was statistically significantly elevated in patients with extraintestinal (FC 0.602) manifestations, while in the group of patients with osteoarticular complications, a significant difference in the level of betaine (FC 1.647) was observed. Conclusions: The analyzed bacterial metabolites of plasma may significantly help in the diagnostic process, and in the monitoring of the disease course and treatment, in a lowly invasive way, as biomarkers after additional research on a larger group of patients.
Effect of a Novel Lavender Extract on Plasma Lipid and Lipoprotein Metabolism, Glucose Tolerance and Adipose Tissue Metabolic Activation: A Preclinical Safety and Efficacy Study
Authors: Kakafoni Georgia , Zvintzou Evangelia , Kyroglou Smaro , Giannatou Katerina , Mparnia Victoria , Vareltzis Patroklos , Kypreos Kyriakos E.
Published: January 2025

Background/Objectives: Lavender has been utilized for its medicinal properties since ancient times, with numerous health benefits reported. This study aimed to valorize solid waste from lavender essential oil production by developing a novel lavender extract from solid lavender residues. The extract’s preclinical safety and efficacy were evaluated with emphasis on plasma lipid and lipoprotein metabolism, glucose tolerance, and adipose tissue metabolic activity. Methods: Male C57BL/6 mice were divided into four groups of five mice each and fed for 30 days with lavender extract encapsulated in 10% maltodextrin, mixed with a standard chow diet. The first group (Lav 1×) received 21.1 mg/kg/day, the second group (Lav 10×) received 211 mg/kg/day, and the third group (Lav 100×) received 2110 mg/kg/day. A placebo group consumed the standard diet without lavender extract. Key outcomes included plasma lipid and lipoprotein profiles, transaminase levels, HDL antioxidant and anti-inflammatory potential, glucose tolerance, and mitochondrial activity in white (WAT) and brown (BAT) adipose tissues. Results: The novel lavender extract induced dose-dependent improvements in lipid and lipoprotein metabolism, glucose tolerance, and adipose tissue activity. The 2110 mg/kg dose (100×) demonstrated the most significant beneficial effects, although it was associated with a slight elevation in hepatic transaminase levels, indicating potential mild hepatic stress. Conclusions: Overall, the novel lavender extract exhibits promising health benefits with no major safety concerns at the tested doses, supporting its potential for therapeutic applications.
The Role of the Chronotype in Developing an Excessive Body Weight and Its Complications—A Narrative Review
Authors: Pelczyńska Marta , Moszak Małgorzata , Wojciechowska Julita , Płócienniczak Anita , Potocki Jan , Blok Joanna , Balcerzak Julia , Zblewski Mikołaj , Bogdański Paweł
Published: January 2025

The chronotype, the personal predisposition towards morning or evening activities, significantly influences health conditions, sleep, and eating regulations. Individuals with evening chronotypes are often at a higher risk for weight gain due to misalignment between their natural tendencies of functioning and social schedules, resulting in insufficient sleep, disruptions in eating habits, and decreased physical activity levels. Often, impaired glucose tolerance and changes in melatonin, adiponectin, and leptin secretion, along with alterations in the clock gene functions in subjects with evening preferences, may be predisposed to obesity. These disturbances contribute to metabolic dysregulation, which may lead to the subsequent onset of obesity complications, such as hypertension, type 2 diabetes, sleep apnea, and liver diseases. Targeting critical components of the circadian system and synchronizing people’s chronotypes with lifestyle conditions could deliver potential strategies for preventing and treating metabolic disorders. Thus, it is recommended to take a personalized chronobiological approach to maintain a normal body weight and metabolic health. Nevertheless, future studies are needed to identify the clear mechanisms between the chronotype and human health. This article provides a narrative review and discussion of recent data to summarize studies on the circadian rhythm in the context of obesity. The manuscript represents a comprehensive overview conducted between August and November 2024 using the National Library of Medicine browser (Medline, Pub-Med, Web of Science).
Severe Cases of Tick-Borne Encephalitis in Northeastern Poland
Authors: Adamczuk Justyna , Chlabicz Magdalena , Koda Natalia , Kondrusik Maciej , Zajkowska Joanna , Czupryna Piotr , Moniuszko-Malinowska Anna
Published: January 2025

Tick-borne encephalitis (TBE) is the most prevalent viral infection of the central nervous system (CNS) in Poland. The disease is characterized by the presence of two stages. The first phase, called the viremic stage, presents with flu-like symptoms, while the second stage of TBE is characterized by damage to the nervous system and may follow a severe and dramatic course. The aim of this paper is to increase the awareness of the potential sequelae after TBE. In this study, we report cases of severe TBE in 36-year-old and 57-year-old female patients. The outcome of TBE varies from patient to patient, but there are some factors that can help to predict the severity of TBE infection. The risk factors presented in these patients were as follows: the monophasic course of TBE, high pleocytosis in cerebrospinal fluid (CSF) and older age. Both of our patients were not vaccinated despite the World Health Organization’s (WHO’s) recommendations. Both patients had no history of travel outside their region of residence prior to the onset of illness. The few risk factors shown in our patients and the serious sequelae of the disease may indicate the need to test patients for possible gene mutations.
Surveillance Following Hepatitis B Surface Antigen Loss: An Issue Requiring Attention
Authors: Huang Shuai-Wen , Long Hong , Huang Jia-Quan
Published: January 2025

Due to the lack of agents that directly target covalently closed circular DNA and integrated HBV DNA in hepatocytes, achieving a complete cure for chronic hepatitis B (CHB) remains challenging. The latest guidelines recommend (hepatitis B surface antigen) HBsAg loss as the ideal treatment target for improving liver function, histopathology, and long-term prognosis. However, even after HBsAg loss, hepatitis B virus can persist, with a risk of recurrence, reactivation, cirrhosis, and hepatocellular carcinoma. Therefore, follow-up and surveillance are still necessary. With increasing treatment options available for achieving HBsAg loss in patients with CHB, developing effective surveillance strategies has become crucial. Recent studies on outcomes following HBsAg loss provide new insights for refining current surveillance strategies, though further improvement is needed through long-term observation and follow-up.
An Update on Anti-COVID-19 Vaccines and the Challenges to Protect Against New SARS-CoV-2 Variants
Authors: Mambelli Fábio , de Araujo Ana Carolina V. S. C. , Farias Jéssica P. , de Andrade Kivia Q. , Ferreira Luis C. S. , Minoprio Paola , Leite Luciana C. C. , Oliveira Sergio C.
Published: January 2025

The COVID-19 pandemic has posed a significant threat to global health systems, with extensive impacts across many sectors of society. The pandemic has been responsible for millions of deaths worldwide since its first identification in late 2019. Several actions have been taken to prevent the disease, including the unprecedented fast development and global vaccination campaigns, which were pivotal in reducing symptoms and deaths. Given the impact of the pandemic, the continuous changes of the virus, and present vaccine technologies, this review analyzes how, so far, we have met the challenge posed by the emergence of new variants and discusses how next-generation pan-coronavirus vaccines, with enhanced longevity and breadth of immune responses, may be tackled with alternative administration routes and antigen delivery platforms. By addressing these critical aspects, this review aims to contribute to the ongoing efforts to achieve long-term control of COVID-19, stimulating the discussion and work on next-generation vaccines capable of facing future waves of infection.
Epidemiology of Chagas Disease in the United States of America: A Short Review and Some Comments
Authors: Klotz Stephen A.
Published: January 2025

The epidemiology of Chagas disease in humans has markedly changed within the past several decades in the United States of America. This report discusses autochthonous cases of Chagas disease as well as disease in immigrants from Latin American countries. Suggestions for epidemiology research and medical care are discussed given the evolving epidemiology of the disease in the United States of America.
Therapeutic Potential of Combined 5% Lifitegrast and Tocopherol Eye Drops in Managing Inflammation and Oxidative Stress in Murine Dry Eye
Authors: Moon Jayoung , Jiang Enying , Liu Jingting , Jin Hui , Yoon Hee Su , Choi Hoon-In , Choi Ji Suk , Qi Hong , Yoon Hyeon-Jeong , Yoon Kyung Chul
Published: January 2025

Background/Objectives: This study aimed to evaluate the therapeutic effects of combined 5% lifitegrast (LF) and tocopherol (TCP) eye drops in a murine experimental dry eye (EDE) model. Methods: Female C57BL/6 were divided into seven groups: untreated controls, EDE control, EDE + 0.05% cyclosporin A (CsA), EDE + tocopherol (TCP), EDE + 5% LF, EDE + 5% LF + TCP (once daily), and EDE + 5% LF + TCP (twice daily). Clinical parameters (tear volume, tear break-up time (TBUT), corneal fluorescein staining score (CFSS), tear film lipid layer grade (TFLLG)) were assessed on days 7 and 14. Goblet cell density in the conjunctiva, CD4+ IFN-γ+ T cells, interleukin levels, reactive oxygen species (ROS) levels, and corneal apoptotic cells were analyzed on day 14. Results: Monotherapy with 0.05% CsA and LF showed improvements in all clinical parameters compared to the EDE control (p < 0.05). Combination therapy groups demonstrated superior improvements in clinical parameters compared to the EDE control, 0.05% CsA, and 5% LF groups. CD4+ IFN-γ+ T cell percentages and ROS levels in the cornea and conjunctiva were markedly reduced in the combination groups compared with the 0.05% CsA and 5% LF groups (p < 0.01). Furthermore, corneal apoptotic cells significantly decreased in the combination groups compared to the 0.05% CsA and TCP groups (p < 0.05). Conclusions: Combined 5% LF and TCP eye drops improved tear film parameters and reduced inflammatory and oxidative stress markers. The combination therapy can mitigate ocular surface damage by managing inflammation and oxidative stress in dry eye.
Sirtuins and Their Implications in the Physiopathology of Gestational Diabetes Mellitus
Authors: Zgutka Katarzyna , Tkacz Marta , Grabowska Marta , Mikołajek-Bedner Wioletta , Tarnowski Maciej
Published: January 2025

Gestational diabetes mellitus (GDM) imposes serious short- and long-term health problems for the mother and her child. An effective therapeutic that can reduce the incidence of GDM and improve long-term outcomes is a major research priority and is very important for public health. Unfortunately, despite numerous studies, the molecular mechanisms underlying GDM are not fully defined and require further study. Chronic low-grade inflammation, oxidative stress, and insulin resistance are central features of pregnancies complicated by GDM. There is evidence of the involvement of sirtuins, which are NAD+-dependent histone deacetylases, in energy metabolism and inflammation. Taking these facts into consideration, the role of sirtuins in the pathomechanism of GDM will be discussed.
Potential Interaction of Pinocembrin with Drug Transporters and Hepatic Drug-Metabolizing Enzymes
Authors: Sangkapat Sirima , Boonnop Rattiporn , Pimta Jeerawat , Chabang Napason , Nutho Bodee , Jutabha Promsuk , Soodvilai Sunhapas
Published: January 2025

Background/Objectives: Pinocembrin is a promising drug candidate for treating ischemic stroke. The interaction of pinocembrin with drug transporters and drug-metabolizing enzymes is not fully revealed. The present study aims to evaluate the interaction potential of pinocembrin with cytochrome P450 (CYP450: CYP2B6, CYP2C9, and CYP2C19) and drug transporters including organic anion transporters (OAT1 and OAT3), organic cation transporters (OCT1 and OCT2), multidrug and toxin extrusion (MATE1 and MATE2, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP). Methods: The interactions of pinocembrin on drug transporters were determined in the Madin–Darby canine kidney (MDCK) cells overexpressing human (h)OAT1 or hOAT3 and in the Chinese hamster ovary (CHO-K1) cells overexpressing hOCT1, hOCT2, hMATE1, or hMATE2. The interactions of pinocembrin with BCRP and P-glycoprotein were determined in Caco-2 cells. The CYP450 enzyme inhibitory activity was assessed by a cell-free CYP450 screening assay. Results: Pinocembrin effectively inhibited the function of OAT1 and OAT3 with a half-inhibitory concentration (IC50) and inhibitory constant (Ki) of ∼2 μM. In addition, it attenuated the toxicity of tenofovir, a substrate of hOAT1, in cells overexpressing hOAT1. Based on the kinetic study and molecular docking, pinocembrin inhibited OAT1 and OAT3 via a competitive inhibition. In contrast to hOAT1 and hOAT3, pinocembrin did not significantly inhibit the function of OCT1, OCT2, MATE1, MATE2, BCRP, and P-glycoprotein. In addition, pinocembrin potently inhibited the activity of CYP2C19, whereas it exhibited low inhibitory potency on CYP2B6 and CYP2C9. Conclusions: The present study reveals the potential drug interaction of pinocembrin on OAT1, OAT3, and CYP2C19. Co-administration with pinocembrin might affect OAT1-, OAT3-, and CYP2C19-mediated drug pharmacokinetic profiles.
Therapeutic Efficacy of Intranasal N-Acetyl-L-Cysteine with Cell-Penetrating Peptide-Modified Polymer Micelles on Neuropathic Pain in Partial Sciatic Nerve Ligation Mice
Authors: Nango Hiroshi , Takahashi Ai , Suzuki Naoto , Kurano Takumi , Sakamoto Saia , Nagatomo Taiki , Suzuki Toyofumi , Kanazawa Takanori , Kosuge Yasuhiro , Miyagishi Hiroko
Published: January 2025

Background/Objectives: We previously demonstrated that the intranasal administration of cell-penetrating Tat peptide-modified carrier, PEG-PCL-Tat, improves drug delivery to the central nervous system. This study aimed to evaluate the potential of the post-onset intranasal administration of N-acetyl-L-cysteine (NAC) combined with PEG-PCL-Tat (NAC/PPT) for neuropathic pain. Methods: Neuropathic pain was induced by partial sciatic nerve ligation (PSNL) in mice. Mechanical allodynia was assessed using the von Frey test on days 11–14 post-ligation. NAC or NAC/PPT was intranasally administered after pain onset. Western blotting and immunohistochemistry were conducted to evaluate ionized calcium-binding adapter molecule 1 (Iba-1) expression and microglial activation in the spinal cord. Results: Mechanical allodynia was exacerbated 11 days after the ligation in PSNL mice. The intranasal administration of NAC alone prevented allodynia exacerbation but failed to provide a therapeutic effect against allodynia in PSNL mice. In contrast, NAC/PPT administration ameliorated PSNL-induced tactile allodynia, with maximum efficacy seen 13 and 14 days after ligation. Western blotting demonstrated that Iba-1 levels tended to increase in PSNL mice compared to controls. This trend of increased Iba-1 levels in PSNL mice was attenuated by the administration of NAC/PPT, but not by NAC alone. Immunohistochemistry revealed an increased number of Iba-1-stained microglia in the ipsilateral spinal cord of PSNL mice, which were significantly suppressed by the administration of NAC/PPT. Conclusions: These results suggest that the post-onset intranasal administration of NAC/PPT ameliorates mechanical allodynia by suppressing microglia induction and that intranasal delivery with PEG-PCL-Tat might be a useful tool for the pharmacological management of neuropathic pain.
Quality by Design-Based Methodology for Development of Titanate Nanotubes Specified for Pharmaceutical Applications Based on Risk Assessment and Artificial Neural Network Modeling
Authors: Saker Ranim , Regdon Géza , Ludasi Krisztina , Sovány Tamás
Published: January 2025

Background: Nanotechnology has been the main area of focus for research in different disciplines, such as medicine, engineering, and applied sciences. Therefore, enormous efforts have been made to insert the use of nanoparticles into the daily routines of different platforms due to their impressive performance and the huge potential they could offer. Among numerous types of nanomaterials, titanate nanotubes have been widely recognised as some of the most promising nanocarriers due to their outstanding profile and brilliant design. Their implementation in pharmaceutical applications is of huge interest nowadays as it could be of fundamental importance in the development of the pharmaceutical industry and therapeutic systems. Methods: In the present work, a risk assessment-based procedure was developed and completed using ANN-based modeling to enable the design and fabrication of titanate nanotube-based drug delivery systems with desired properties, based on the critical analysis and evaluation of data collected from published articles regarding titanate nanotube preparation using the hydrothermal treatment method. Results: This analysis is presented as an integrated pathway for titanate nanotube preparation and utilization in a proper way that meets the strict requirements of pharmaceutical systems (quality, safety, and efficacy). Furthermore, a reasonable estimation of the factors affecting titanate nanotube preparation and transformation from traditional uses to novel pharmaceutical ones was established with the aid of a quality by design approach and risk assessment tools, mainly an Ishikawa diagram, a risk estimation matrix, and Pareto analysis. Conclusions: To the best of our knowledge, this is the first article using the QbD approach to suggest a systematic method for the purpose of upgrading TNT use to the pharmaceutical domain.
Tm-Doped Fiber Laser Cladding Pumped by a Pulsed Er-Doped Fiber Laser with a 110 μm Core
Authors: Khegai Aleksandr , Firstov Sergei , Riumkin Konstantin , Lipatov Denis , Melkumov Mikhail
Published: January 2025

Pulsed laser sources operating in the spectral range of 1.8 to 2.1 μm draw considerable attention due to their wide range of practical applications in many areas, including medicine, sensing, materials processing, etc. In this work, we propose a pulsed Tm-doped fiber laser scheme operating in the 2 μm spectral region with pulsed pumping at 1.57 μm. The pump source consisted of a series-connected Er-Yb pulsed master oscillator and an EDFA emitting ∼400 μs pulses with an energy of 9.3 mJ. Using this setup, we made a Tm-doped fiber laser that provided 2 mJ pulses in the 2 μm spectral region with a slope efficiency of 28% from pulses at 1.57 μm.
Random Emission and Control of Whispering Gallery Mode Using Flexible Optical Fiber
Authors: Cao Bingyang , He Zhen , Zhang Weili
Published: January 2025

Axially uniform optical fibers provide a low-cost, scalable platform for the emission of whispering gallery mode (WGM) lasers. This paper proposes a method for generating and controlling WGM lasers based on the design of a flexible optical fiber array structure. By adjusting the spacing between the flexible fibers, the coupling relationship between different WGM modes is modulated, achieving a transition from regular to random WGM (R-WGM) mechanisms. Additionally, the application of this laser in information security encryption is demonstrated and explored.
Response of Plant Community Characteristics and Soil Factors to Topographic Variations in Alpine Grasslands
Authors: Liang Qinyang , Zhao Jinmei , Wang Zixin , Wang Xingyi , Fu Dianxia , Li Xiaogang
Published: January 2025

Topography has an important influence on plant–soil relationships. However, research on plant–soil relationships in alpine grassland at the slope aspect and slope position scales is currently inadequate. In this paper, based on the topographic and geomorphological characteristics of the study area, alpine grassland with typical slope aspect and slope position conditions was selected as the research object. Through field investigations and laboratory research to reveal how the characteristics of the alpine grassland plant community and soil factors respond to changes in topography. The results show: Slope aspect and slope position changes significantly affect alpine grassland plant communities and soil properties. In terms of the dominant species in plant communities, the sunny slopes were dominated by Poaceae and the shady slopes were dominated by Polygonaceae. Plant community characterization variables showed a decreasing trend from shady to sunny slopes and bottom to top. The soil factors showed significant differences among the six types of topography (p < 0.05), and the magnitude order in different slope aspects and positions was basically shady slope > sunny slope and bottom > middle and top. Correlation analysis showed that there were good correlations between soil organic carbon (SOC), soil water content (SWC), total nitrogen (TN), pH, and plant community characteristics in alpine grassland. In addition, redundancy analyses (RDA) indicated that the divergence in plant community characteristics was primarily driven by the change difference in SOC along topographic gradients. Our findings may provide a scientific basis for the restoration and utilization of alpine grassland vegetation and the evaluation of the ecological environment in this region.
Exploring Fungal Biodiversity in Crop Rotation Systems: Impact of Soil Fertility and Winter Wheat Cropping
Authors: Šeremešić Srdjan , Tančić Živanov Sonja , Rajković Miloš , Aćin Vladimir , Milić Stanko , Babec Brankica , Jovanović Snežana
Published: January 2025

This study investigated soil fungal biodiversity in wheat-based crop rotation systems on Chernozem soil within the Pannonian Basin, focusing on the effects of tillage, crop rotation, and soil properties. Over three years, soil samples from ten plots were analyzed, revealing significant fungal diversity with Shannon–Wiener diversity indices ranging from 1.90 in monoculture systems to 2.38 in a fertilized two-year crop rotation. Dominant fungi, including Fusarium oxysporum, Penicillium sp., and Aspergillus sp., showed distinct preferences for soil conditions such as pH and organic matter (OM). Conservation tillage significantly enhanced fungal diversity and richness, with the highest diversity observed in a three-year crop rotation system incorporating cover crops, which achieved an average winter wheat yield of 7.0 t ha−1—47% higher than unfertilized monoculture systems. Increased OM and nitrogen levels in these systems correlated with greater fungal abundance and diversity. Canonical correspondence analysis revealed strong relationships between fungal communities and soil properties, particularly pH and calcium carbonate content. These findings highlight the importance of tailored crop rotation and tillage strategies to improve soil health, enhance microbial biodiversity, and boost agricultural sustainability in temperate climates, providing valuable insights for mitigating the impacts of intensive farming and climate change.
In Situ Phytoremediation of Mine Tailings with High Concentrations of Cadmium and Lead Using Dodonaea viscosa (Sapindaceae)
Authors: Acosta-Núñez Luis Fernando , Mussali-Galante Patricia , Castrejón-Godínez María Luisa , Rodríguez-Solís Alexis , Castañeda-Espinoza Joel Daniel , Tovar-Sánchez Efraín
Published: January 2025

The waste generated during metal mining activities contains mixtures of heavy metals (HM) that are not biodegradable and can accumulate in the surrounding biota, increasing risk to human and environmental health. Plant species with the capacity to grow and develop on mine tailings can be used as a model system in phytoremediation studies. Dodonaea viscosa (L.) Jacq. is a shrub with wide geographical distribution and the ability to establish itself in mine tailings. The Sierra de Huautla Biosphere Reserve in Mexico contains a metallurgic district where mining activities have generated 780 million kg of waste with large concentrations of toxic heavy metals, mainly cadmium and lead. The present study evaluated the phytoremediation potential of D. viscosa in in situ conditions on soils contaminated with HMs (exposed) and reference sites (non-exposed) for one year. Also, the effects of cadmium (Cd) and lead (Pb) exposure in D. viscosa were analyzed via DNA damage (comet assay) morphological and physiological characters in exposed vs non-exposed individuals. The concentration of Cd and Pb was measured through atomic absorption spectrophotometry in the roots and leaves of plants. In total, 120 D. viscosa individuals were established, 60 growing in exposed and 60 in non-exposed soils. Exposed individuals of D. viscosa hyperaccumulated Cd and Pb in roots and leaves. At the end of the experiment, eight out of twelve characters under evaluation decreased significantly in HM-exposed plants in relation to individuals growing in non-exposed soils, except for stomatal index, stomatal coverage, and fresh leaf biomass. The micro-morphological and physiological traits of D. viscosa were not influenced by Cd and Pb bioaccumulation. In contrast, the bioaccumulation of Cd and Pb significantly influenced the macro-morphological characters and genetic damage; this last biomarker was 3.2 times higher in plants growing in exposed sites. The bioconcentration factor (BCF) of Cd and Pb in root and leaf tissue increased significantly over time. The mean BCF in root and leaf tissue was higher for Pb (877.58 and 798.77) than for Cd (50.86 and 23.02). After 12 months of exposure, D. viscosa individuals growing on mine tailing substrate showed that the total HM phytoextraction capacity was 7.56 kg∙ha−1 for Pb and 0.307 kg∙ha−1 for Cd. D. viscosa shows potential for phytoremediation of soils contaminated with Cd and Pb, given its capacity for establishing and developing naturally in contaminated soils with HM. Along with its bioaccumulation, biomass production, abundance, and high levels of bioconcentration factors, but without affecting plant development and not registering associated herbivores, it may incorporate HM into the trophic chain.
Genome-Wide Identification and Expression Analysis of the CAMTA Gene Family in Roses (Rosa chinensis Jacq.)
Authors: Su Wanyi , Deng Yuzheng , Pan Xuejuan , Li Ailing , Zhu Yongjie , Zhang Jitao , Lu Siting , Liao Weibiao
Published: January 2025

Calmodulin-binding transcription activator (CAMTA), as one of the transcription factors, is involved in performing important functions in modulating plant stress responses and development in a Ca2+/CaM-driven modus. However, genome-scale analysis of CAMTA has not been systemically investigated in roses. Rose (Rosa chinensis Jacq.) CAMTA gene family members were identified and bioinformatically analyzed to investigate their expression characteristics in plant hormonal responses. The results show that a total of five rose CAMTA genes were identified. Chromosomal localization shows that the RcCAMTA gene members were located on chromosomes 2, 4, and 7. Physicochemical property analysis shows that its CDS sequence length ranges from 500 to 1070 bp, the molecular weight ranges from 55,531.60 to 120,252.98 Da, and the isoelectric point is from 5.04 to 8.54. Phylogenetic analysis shows that rose CAMTA genes are classified into three subfamilies. Conservative motif analysis reveals the presence of motif 1, motif 3, motif 5, motif 7, and motif 10 in all the RcCAMTA genes. The cis-acting element prediction results show that the rose CAMTA gene family contains phytohormone-signaling response elements, abiotic stress responses, light responses, and other elements, most of which are hormone-signaling response elements. From the expression levels of RcCAMTA genes, the CAMTA family’s genes in roses have different spatial expression patterns in different tissues. The qRT-PCR analysis showed that all five rose CAMTA genes responded to salicylic acid (SA). RcCAMTA3 was significantly induced by abscisic acid (ABA), and RcCAMTA2 was significantly induced by 1H-indole-3-acetic acid (IAA) and methyl jasmonate (MeJA). Thus, we provide a basic reference for further studies about the functions of CAMTA proteins in plants.