bluuebunny/crossref_metadata_2025 huggingface dataset:
Horticulture Plants’ Stress Physiology
Authors: Manghwar Hakim
Published: November 2024

The growth and productivity of horticultural crops have been significantly impacted by human activities and global climate change [...]
Evaluation of Different Anti-Browning Treatments on the Quality of Four Colombian Potato Varieties
Authors: Salazar-Montoya Omar , Idárraga-Arcila Verónica , Torres-Martínez Paula , Duarte-Correa Yudy
Published: November 2024

The increasing demand for fresh and convenient foods has led to the production of Minimally Processed Products (MPPs), which are suitable for culinary and industrial uses. However, cutting potatoes can trigger browning, negatively impacting their sensory and nutritional quality. This study aimed to evaluate different anti-browning methods on Colombian potato varieties (Diacol Capiro, Pastusa, Nevada, and Sabanera) as raw materials for the development of MPPs. The physicochemical properties evaluated included moisture, pH, acidity, enzymatic activity, total phenolic content, vitamin C, and browning index. The anti-browning treatments involved immersing the potatoes in citric acid, ascorbic acid, and garlic extract. Evaluations were carried out over a 15-day storage period in refrigerated conditions. The results indicated that the Sabanera variety had the highest browning index, followed by Nevada, while Diacol Capiro and Pastusa showed lower browning indices, even without the use of technological coadjuvants. Among the treatments, citric acid proved to be the most effective across all varieties, with Diacol Capiro exhibiting the least browning after 15 days. Garlic extract was the least effective against browning. The sensory analysis indicated that an acidic descriptor was noted for both treated (with citric acid) and untreated (control) Diacol Capiro potatoes at similar intensities, suggesting that citric acid did not negatively affect the sensory quality and/or was masked during cooking, enhancing overall quality. In conclusion, the Diacol Capiro variety treated with 1% citric acid is the most appropriate choice for use as a raw material for MPPs without compromising sensory quality.
The Impact of Climate Change on Tomato Water Footprint under Irrigation with Saline Water in a Kairouan Irrigated Area (Tunisia Center)
Authors: Khaskhoussy Khawla , Zarai Besma , Zouari Marwa , Nasr Zouhair , Hachicha Mohamed
Published: November 2024

The concept of the water footprint (WF) has not adequately explored the combined effects of climate change and salinity. For this aim, the effects of future climate conditions on tomato WF irrigated with moderately saline water (EC = 2.9 dS m−1) were examined, considering an expected increase in salinity reaching 5.9 dS m−1 by 2050. Reference evapotranspiration (ETo), effective rainfall (ER), tomato crop evapotranspiration (ETc), leaching requirement (LR), net irrigation requirement (NIR), and tomato yield were estimated using CropWat and AquaCrop models. The blue (WFBlue), green (WFGreen), gray (WFGray), and total WF (TWF) were calculated. Results showed that ETo, ETc, and ER are expected to increase, while tomato yields will show a slight decrease. NIR is expected to increase depending on climate change scenarios and the increasing salinity of water irrigation. Calculated WF components showed significant increases, which consequently led to an increase in WFT exceeding the Tunisian national and regional levels by 15% and 18% between 2023 and 2050 under two scenarios, RCP4.5 and RCP8.5. The results highlighted the importance of WF for developing adaptation strategies to manage limited water resources, while advanced research on a large scale based on smart assessment tools is required to find best practices for water use reduction.
Simulation of Seawater Intrusion and Upconing Processes in Mediterranean Aquifer in Response to Climate Change (Plana de Castellón, Spain)
Authors: Almazan-Benitéz Barbara del R. , Esteller-Alberich Maria V. , Renau-Pruñonosa Arianna , Expósito-Castillo José L.
Published: November 2024

In coastal regions, groundwater is often the only freshwater resource available for human consumption, agriculture, and other productive activities. From a management point of view, it is essential to understand the processes that occur in a coastal aquifer affected by seawater intrusion and upconing processes and evaluate their potential response to climate change as these scenarios usually indicate a decrease in aquifer recharge. Therefore, the dynamics of seawater intrusion and the upconing process in the Plana de Castellón aquifer on the Mediterranean coast were analysed by building and calibrating a new numerical model of flow and transport using the MODFLOW and SEAWAT codes. The model was used to examine two Shared Socioeconomic Pathway (SSP) climate change scenarios (SSP1–2.6 and SSP5–8.5) when considering field data with constant extraction conditions. The results suggest that by 2050, groundwater levels could rise by 0.18 m (on average) in the SSP1–2.6 scenario and by 0.12 m for the SSP5–8.5 scenario. In these cases, aquifer recharge and groundwater discharge to the sea could increase compared to the historical period, as precipitation is not expected to decrease significantly during this timeframe, even in the most unfavourable scenario (SSP5–8.5). The result would be the attenuation of seawater intrusion and a decrease in the volume of the aquifer that is affected by the upconing process, resulting in total dissolved solids values below 2000 mg/L. The innovation of this research lies in the fact that the numerical model allowed the dynamics of seawater intrusion and the upconing process to be adequately represented, especially in the latter process, as it was not possible to model it with real data in another study. These results can improve and facilitate decision-making for the management of the aquifer and contribute to plans for future exploitation strategies.
Quantile Spillovers and Connectedness Between Real Estate Investment Trust, the Housing Market, and Investor Sentiment
Authors: Hadad Elroi , Le Thai Hong , Luong Anh Tram
Published: November 2024

This paper examines the quantile connectedness between Real Estate Investment Trusts (REITs), housing market sentiment, and stock market sentiment in the U.S. over the period between January 2014 and June 2022 using the quantile vector autoregression (QVAR) model. We find modest spillover effects at the median quantile (8.51%), which become more pronounced at the extreme tails (between 50.51% and 59.73%). The COVID-19 pandemic amplifies these interconnections. REITs are net receivers at the median but net transmitters at extreme quantiles, while stock market sentiment mainly transmits during normal conditions and receives in highly bullish markets. Home purchase sentiment shifts from fluctuating roles before the pandemic to being a net transmitter post-2021. Overall, negative shocks have a greater impact than positive ones, and REITs exhibit stock-like behavior. These findings underscore the importance for fund managers and investors to consider sentiment volatility in both stock and real estate markets, especially during extreme market conditions.
Is Fluoride Blameless?—The Influence of Fluorine Compounds on the Invasiveness of the Human Glioma-like Cell Line U-87
Authors: Żwierełło Wojciech , Maruszewska Agnieszka , Skórka-Majewicz Marta , Wszołek Agata , Gutowska Izabela
Published: November 2024

Glioblastoma remains one of the most treatment-resistant and malignant human cancers. Given the documented harmful effects of fluoride on the developing central nervous system and the rising incidence of brain tumors, especially among children, it is pertinent to explore the role of environmental toxins, including fluoride compounds, in the context of brain cancer. This study represents the first investigation into the influence of fluoride on mechanisms related to the invasiveness of human glioblastoma cells. We examined the effects of sodium fluoride (NaF) exposure on the migratory and invasive abilities of the U-87 human glioblastoma cell line, assessing levels of metalloproteinases MMP-2 and MMP-9 secreted by these cells. Additionally, the activation of metabolic pathways associated with invasiveness, including AKT and NF-κB, was analyzed. Our results suggest that the effects induced by NaF at physiologically high concentrations (0.1–10 µM) in U-87 glioblastoma cells may promote a pro-invasive phenotype.
Study of Host-Guest Interaction and In Vitro Neuroprotective Potential of Cinnamic Acid/Randomly Methylated β-Cyclodextrin Inclusion Complex
Authors: De Gaetano Federica , Leggio Loredana , Celesti Consuelo , Genovese Fabio , Falcone Marco , Giofrè Salvatore Vincenzo , Iraci Nunzio , Iraci Nunzio , Ventura Cinzia Anna
Published: November 2024

Cinnamic acid (CA) has many beneficial effects on human health. However, its poor water solubility (0.23 g/L, at 25 °C) is responsible for its poor bioavailability. This drawback prevents its clinical use. To overcome the solubility limits of this extraordinary natural compound, in this study, we developed a highly water-soluble inclusion complex of CA with randomly methylated-β-cyclodextrin (RAMEB). The host-guest interaction was explored in liquid and solid states by UV-Vis titration, phase solubility analysis, FT-IR spectroscopy, and 1H-NMR. Additionally, molecular modeling studies were carried out. Both experimental and theoretical studies revealed a 1:1 CA/RAMEB inclusion complex, with a high apparent stability constant equal to 15,169.53 M−1. The inclusion complex increases the water solubility of CA by about 250-fold and dissolves within 5 min. Molecular modeling demonstrated that CA inserts its phenyl ring into the RAMEB cavity with its propyl-2-enoic acid tail leaning from the wide rim. Finally, a biological in vitro study of the inclusion complex, compared to the free components, was performed on the neuroblastoma SH-SY5Y cell line. None of them showed cytotoxic effects at the assayed concentrations. Of note, the pretreatment of SH-SY5Y cells with CA/RAMEB at 10, 30, and 125 µM doses significantly counteracted the effect of the neurotoxin MPP+, whilst CA and RAMEB alone did not show any neuroprotection. Overall, our data demonstrated that inclusion complexes overcome CA solubility problems, supporting their use for clinical applications.
Selected Markers of Inflammation in the Saliva of Children Infected with Helicobacter pylori
Authors: Zakrzewski Mateusz , Gornowicz Agnieszka , Zakrzewska Magdalena , Bielawska Anna , Maciorkowska Elżbieta
Published: November 2024

Helicobacter pylori has been of interest to scientists and clinicians for many years, often causing diagnostic difficulties, especially in the youngest age group, in children. The presence of this bacterium in the population depends on the geographic region. However, it is assumed that even half of the world’s population may be infected with H. pylori. Children infected with H. pylori—the study group (Hp(+)) and control group (Hp(−)), were chosen for further examination. The aim of the study was to analyze the concentrations of selected inflammatory markers in saliva (TNF-α, IL-8) and other markers (neutrophil defensin-1, sICAM-1, calprotectin, metalloproteinase-9, metalloproteinase-2, lactotransferrin, TLR-2) using ELISA technique. We confirmed the increased concentrations of IL-8, ND-1, and TLR-2 in the group of children infected with Helicobacter pylori. Moreover, there was also a positive, significant correlation between the concentration of ND-1 and MMP-2, sICAM-1, and calprotectin as well as MMP-9 and MMP-2 in the group of infected children. The study created new possibilities of insight into the pathogenetic mechanisms of developing inflammation in the mouth. This type of comprehensive research is also used to monitor the current disease process and create new opportunities for better in-depth diagnostics of children infected with H. pylori.
Mitochondrial Transplantation Ameliorates Pulmonary Fibrosis by Suppressing Myofibroblast Activation
Authors: Lee Seo-Eun , Yu Shin-Hye , Kim In-Hyeon , Kang Young Cheol , Kim Yujin , Yeo Jeong Seon , Lim Jun Hyeok , Kwon Iksun , Kim Je-Hein , Park Se-Woong , Chang Mi-Yoon , Han Kyuboem , Kim Sung-Hwan , Kim Chun-Hyung
Published: November 2024

Idiopathic pulmonary fibrosis (IPF) is a pulmonary disease characterized by excessive extracellular matrix protein deposition in the lung interstitium, subsequently causing respiratory failure. IPF still has a high medical unmet requirement due to the lack of effective treatments to inhibit disease progression. The etiology of IPF remains unclear, but mitochondrial dysfunction is considered to be associated with IPF development. Therefore, targeting mitochondrial abnormalities would be a promising strategy for treating IPF. Recently, exogenous mitochondrial transplantation has been beneficial for treating mitochondrial dysfunction. The current study aimed to examine the therapeutic effect of mitochondrial transplantation on IPF in vitro and in vivo. Mitochondria were isolated from human umbilical cord mesenchymal stem cells, referred to as PN-101. Human lung fibroblasts and human bronchial epithelial cells were exposed to transforming growth factor-β, followed by PN-101 treatment to determine the in vitro efficacy of mitochondrial transplantation. An IPF mouse model established by a single intratracheal instillation of bleomycin was utilized to determine the in vivo efficacy of the intravenously treated mitochondria. PN-101 attenuated mitochondrial damage, inhibited EMC production, and suppressed epithelial-to-mesenchymal transition in vitro. Additionally, intravenous PN-101 administration alleviated bleomycin-induced fibrotic processes in the IPF mouse model with a therapeutic context. Our data indicate that PN-101 is a novel and potential therapeutic agent for IPF.
Self-Assembled Gold Nanoparticles as Reusable SERS Substrates for Polyphenolic Compound Detection
Authors: Pavlova Arina , Maleeva Ksenia , Moskalenko Ivan V. , Belyaev Vadim , Zhukov Mikhail V. , Kirilenko Demid , Bogdanov Kirill V. , Smirnov Evgeny
Published: November 2024

Natural polyphenolic compounds play a pivotal role in biological processes and exhibit notable antioxidant activity. Among these compounds, chlorogenic acid stands out as one of the most widespread and important polyphenols. The accurate detection of chlorogenic acid is crucial for ensuring the quality and classification of the raw materials used in its extraction, as well as the final products in the food, pharmaceutical, and cosmetics industries that contain this bioactive compound. Raman spectroscopy emerges as a powerful analytical tool, particularly in field applications, due to its versatility and sensitivity, offering both qualitative and quantitative analyses. By using the self-assembly of gold nanoparticles at liquid–liquid interfaces and the developed “aqua-print” process, we propose a facile and inexpensive route to fabricate enhanced substrates for surface-enhanced Raman spectroscopy with high reproducibility. To ensure substrate reliability and accurate molecule detection in SERS experiments, a benchmarking procedure was developed. This process involved the use of non-resonant rhodamine 6G dye in the absence of charge transfer and was applied to all synthesized nanoparticles and fabricated substrates. The latter revealed the highest enhancement factor of 4 × 104 for 72 nm gold nanoparticles among nanoparticle diameters ranging from 14 to 99 nm. Furthermore, the enhanced substrate was implemented in the detection of chlorogenic acid with a concentration range from 10 μM to 350 μM, demonstrating high accuracy (R2 > 99%). Raman mapping was employed to validate the good uniformity of the signal (the standard deviation was below 15%). The findings of this study were also supported by DFT calculations of the theoretical Raman spectra, demonstrating the formation of the chlorogenic acid dimer. The proposed method is strategically important for the development of the class of in-field methods to detect polyphenolic compounds in raw materials such as plants, extracted plant proteins, and polyphenolic compounds.
Interaction of Human Respiratory Syncytial Virus (HRSV) Matrix Protein with Resveratrol Shows Antiviral Effect
Authors: Rodrigues Thaina , Busso Jefferson de Souza , Dias Raphael Vinicius Rodrigues , Ottenio Lourenço Isabella , de Sa Jessica Maróstica , Carvalho Sidney Jurado de , Caruso Icaro Putinhon , Souza Fatima Pereira de , Fossey Marcelo Andres
Published: November 2024

The respiratory syncytial virus (RSV) matrix protein plays key roles in the virus life cycle and is essential for budding, as it stimulates the optimal membrane curvature necessary for the emergence of viral particles. Resveratrol, a polyphenol (3,4′,5-trihydroxy-trans-stilbene) produced by plants, exhibits pharmacological effects, including anti-inflammatory and antiviral activities. In this study, resveratrol was tested in HEp-2 (Epidermoid carcinoma of the larynx cell) cells for its post-infection effects, and recombinant M protein was produced to characterize the biophysical mechanisms underlying this interaction. The CC50 (Cytotoxic concentration 50%) value for resveratrol was determined to be 297 μM over 48 h, and the results from the HEp-2 cell cultures demonstrated a viral inhibition of 42.7% in the presence of resveratrol, with an EC50 (Half maximal effective concentration) of 44.26 μM. This mechanism may occur through interaction with the M protein responsible for the budding of mature viral particles. Biophysical assays enabled us to characterize the interaction of the M/resveratrol complex as an entropically driven bond, guided by hydrophobic interactions at the dimerization interface of the M protein, which is essential for the stabilization and formation of the oligomers necessary for viral budding. These findings suggest that one of the targets for resveratrol binding is the M protein, indicating a potential site for blocking the progression of the infection.
High Absorption and Elasticity of a Novel Transgenic Silk with Egg Case Silk Protein from Nephila clavata
Authors: Wang Yichen , Lin Yuhang , Luo Yongkang , Zeng Di , He Haibo , Zhao Tianfu
Published: November 2024

Spider silk is part of a special class of natural protein fibers that have high strength and toughness: these materials have excellent comprehensive properties that are not found in other natural fibers (including silk) or most synthetic fibers. Spider egg case filaments have good hardness, can resist water, can protect spider eggs from external threats, have a significantly high initial modulus and high moisture absorption rate, and are expected to be used as a new generation of environmentally friendly natural polymer fibers and biomaterials. However, spiders are predatory and difficult to rear in large numbers, and it is also difficult to obtain spider egg case filaments in large quantities. Silkworms and spiders have a similar spinning system, and the use of transgenic technology in silkworms can obtain stable and high-yield exogenous gene proteins for a long time, representing an ideal bioreactor for the production of spider silk. In this study, the eukaryotic bioreactor and piggyBac transposon system were employed to recombinantly introduce the egg case silk protein of Nephila clavata (Nc-CYSP1) into the silkworm in the silkworm heavy-chain expression system. The results revealed that the silk glands produced a new type of transgenic silk with a significantly high initial modulus and high moisture absorption. In summary, this study provides an experimental reference for future research on the large-scale production and application of spider egg case filamentous protein, with great application prospects in the development of new environmentally friendly materials.
Diverse Cyclization Pathways Between Nitriles with Active α-Methylene Group and Ambiphilic 2-Pyridylselenyl Reagents Enabled by Reversible Covalent Bonding
Authors: Artemjev Alexey A. , Sapronov Alexander A. , Kubasov Alexey S. , Peregudov Alexander S. , Novikov Alexander S. , Egorov Anton R. , Khrustalev Victor N. , Borisov Alexander V. , Matsulevich Zhanna V. , Shikhaliyev Namiq G. , Nenajdenko Valentine G. , Gomila Rosa M. , Frontera Antonio , Kritchenkov Andreii S. , Tskhovrebov Alexander G.
Published: November 2024

Herein, we describe a novel coupling between ambiphilic 2-pyridylselenyl reagents and nitriles featuring an active α-methylene group. Depending on the solvent employed, this reaction can yield two distinct types of cationic pyridinium-fused selenium-containing heterocycles, 1,3-selenazolium or 1,2,4-selenadiazolium salts, in high yields. This is in contrast to what we observed before for other nitriles. Notably, the formation of selenadiazolium is reversible, gradually converting into the more thermodynamically stable selenazolium product in solution. Our findings reveal, for the first time, the reversible nature of 1,3-dipolar cyclization between the CN triple bond and 2-pyridylselenyl reagents. Nitrile substitution experiments in the adducts confirmed the dynamic nature of this cyclization, indicating potential applications in dynamic covalent chemistry. DFT calculations revealed the mechanistic pathways for new cyclizations, suggesting a concerted [3 + 2] cycloaddition for the formation of selenadiazolium rings and a stepwise mechanism involving a ketenimine intermediate for the formation of selenazolium rings. Natural bond orbital analysis confirmed the involvement of σ-hole interactions and lone pair to σ* electron donation in these processes. Additionally, theoretical investigations of σ-hole interactions were performed, focusing on the selenium-centered contacts within the new compounds.
Momordica charantia Extract Ameliorates Melanoma Cell Proliferation and Invasion into Mouse Lungs by Suppressing PAX3 Expression
Authors: Hiramoto Keiichi , Oikawa Hirotaka
Published: November 2024

Melanomas, which develop on malignant transformations of melanocytes, are highly malignant and prone to metastasis; therefore, effective drugs are required. The Momordica charantia (MC) extract has been shown to suppress cancer cell proliferation and invasion; however, the effect of the MC extract on melanoma in living organisms remains unclear. In this study, we investigated the mechanism underlying the amelioration of melanoma cell extravasation into mouse lungs by the MC extract. Male C57BL/6j mice (aged 8 weeks) were injected with B16 melanoma cells (1 × 105 cells/mouse). Subsequently, they were orally administered the MC extract daily for 2 weeks; mouse lung samples were obtained on the final day and analyzed. The MC extract ameliorated melanoma proliferation and infiltration into the lungs caused by melanoma cell treatment. It also increased phosphatase and tensin homolog deletion from chromosome 10 and suppressed paired box gene 3 (PAX3) and the phosphatidylinositol trisphosphate/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin complex 1 signaling. Furthermore, it decreased microphthalmia-associated transcription factors and induced the suppression of cyclin-dependent kinase 2, hepatocyte growth factor receptor, B-cell/CLL lymphoma 2, and Ras-related proteins. Our findings suggest that the MC extract suppresses tumor survival genes by regulating PAX3, thereby ameliorating melanoma proliferation and invasion.
BK Polyomavirus Infection in Kidney Transplantation: A Comprehensive Review of Current Challenges and Future Directions
Authors: Nourie Nicole , Boueri Céline , Tran Minh Hoang , Divard Gillian , Lefaucheur Carmen , Salmona Maud , Gressens Simon B. , Louis Kevin
Published: November 2024

BK polyomavirus (BKPyV) infection of the kidney graft remains a major clinical issue in the field of organ transplantation. Risk factors for BKPyV-associated nephropathy (BKPyVAN) and molecular tools for determining viral DNA loads are now better defined. BKPyV DNAemia in plasma, in particular, plays a central role in diagnosing active infection and managing treatment decisions. However, significant gaps remain in the development of reliable biomarkers that can anticipate BKPyV viremia and predict disease outcomes. Biomarkers under active investigation include urine-based viral load assays, viral antigen detection, and immune responses against BKPyV, which may offer more precise methods for monitoring disease progression. In addition, treatment of BKPyVAN is currently based on immunosuppression minimization, while the role of adjunctive therapies remains an area of active research, highlighting the need for more personalized treatment regimens. Ongoing clinical trials are also exploring the efficacy of T-cell-based immunotherapies. The clinical management of BKPyV infection, based on proactive virological monitoring, immune response assessment, integrated histopathology, and timely immunosuppression reduction, is likely to reduce the burden of disease and improve outcomes in kidney transplantation.
Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma
Authors: Zolotareva Karina , Dotsenko Polina A. , Podkolodnyy Nikolay , Ivanov Roman , Makarova Aelita-Luiza , Chadaeva Irina , Bogomolov Anton , Demenkov Pavel S. , Ivanisenko Vladimir , Oshchepkov Dmitry , Ponomarenko Mikhail
Published: November 2024

Primary open-angle glaucoma (POAG) is the most common form of glaucoma. This condition leads to optic nerve degeneration and eventually to blindness. Tobacco smoking, alcohol consumption, fast-food diets, obesity, heavy weight lifting, high-intensity physical exercises, and many other bad habits are lifestyle-related risk factors for POAG. By contrast, moderate-intensity aerobic exercise and the Mediterranean diet can alleviate POAG. In this work, we for the first time estimated the phylostratigraphic age indices (PAIs) of all 153 POAG-related human genes in the NCBI Gene Database. This allowed us to separate them into two groups: POAG-related genes that appeared before and after the phylum Chordata, that is, ophthalmologically speaking, before and after the camera-type eye evolved. Next, in the POAG-related genes’ promoters, we in silico predicted all 3835 candidate SNP markers that significantly change the TATA-binding protein (TBP) affinity for these promoters and, through this molecular mechanism, the expression levels of these genes. Finally, we verified our results against five independent web services—PANTHER, DAVID, STRING, MetaScape, and GeneMANIA—as well as the ClinVar database. It was concluded that POAG is likely to be a symptom of the human self-domestication syndrome, a downside of being civilized.
Coumarin Derivative Hybrids: Novel Dual Inhibitors Targeting Acetylcholinesterase and Monoamine Oxidases for Alzheimer’s Therapy
Authors: Żołek Teresa , Purgatorio Rosa , Kłopotowski Łukasz , Catto Marco , Ostrowska Kinga
Published: November 2024

Multi-target-directed ligands (MTDLs) represent a promising frontier in tackling the complexity of multifactorial pathologies like Alzheimer’s disease (AD). The synergistic inhibition of MAO-B, MAO-A, and AChE is believed to enhance treatment efficacy. A novel coumarin-based molecule substituted with O-phenylpiperazine via three- and four-carbon linkers at the 5- and 7-positions, has been identified as an effective MTDL against AD. Employing a medicinal chemistry approach, combined with molecular docking, molecular dynamic simulation, and ΔGbind estimation, two series of derivatives emerged as potent MTDLs: 8-acetyl-7-hydroxy-4-methylcoumarin (IC50: 1.52–4.95 μM for hAChE, 6.97–7.65 μM for hMAO-A) and 4,7-dimethyl-5-hydroxycoumarin (IC50: 1.88–4.76 μM for hMAO-B). They displayed binding free energy (ΔGbind) of −76.32 kcal/mol (11) and −70.12 kcal/mol (12) against AChE and −66.27 kcal/mol (11) and −62.89 kcal/mol (12) against MAO-A. It is noteworthy that compounds 11 and 12 demonstrated efficient binding to both AChE and MAO-A, while compounds 3 and 10 significantly reduced MAO-B and AChE aggregation in vitro. These findings provide structural templates for the development of dual MAO and AChE inhibitors for the treatment of neurodegenerative diseases.
Therapeutic Potential of Natural Compounds to Modulate WNT/β-Catenin Signaling in Cancer: Current State of Art and Challenges
Authors: Gajos-Michniewicz Anna , Czyz Malgorzata
Published: November 2024

Targeted therapies and immunotherapies have improved the clinical outcome of cancer patients; however, the efficacy of treatment remains frequently limited due to low predictability of response and development of drug resistance. Therefore, novel therapeutic strategies for various cancer types are needed. Current research emphasizes the potential therapeutic value of targeting WNT/β-catenin dependent signaling that is deregulated in various cancer types. Targeting the WNT/β-catenin signaling pathway with diverse synthetic and natural agents is the subject of a number of preclinical studies and clinical trials for cancer patients. The usage of nature-derived agents is attributed to their health benefits, reduced toxicity and side effects compared to synthetic agents. The review summarizes preclinical studies and ongoing clinical trials that aim to target components of the WNT/β-catenin pathway across a diverse spectrum of cancer types, highlighting their potential to improve cancer treatment.
Fusarium sacchari CFEM Proteins Suppress Host Immunity and Differentially Contribute to Virulence
Authors: Hong Tianshu , Wang Shichao , Luo Zhiyuan , Ren Qianqian , Wu Deng , Wang Lulu , Bao Yixue , Yao Wei , Zhang Muqing , Hu Qin
Published: November 2024

The pathogen Fusarium sacchari is responsible for the devastating pokkah boeng disease, which causes significant economic losses in sugarcane production. However, the mechanisms by which it affects plant immunity remain largely unknown. Common in Fungal Extracellular Membrane (CFEM) domain proteins have been implicated in fungal growth, infection processes, and pathogenicity. In this study, we identified three FsCFEM proteins (Fs08184, Fs10706, and Fs13617) that mediate the broad-spectrum suppression of the immune responses induced by typical effectors. A further analysis demonstrated that Fs08184, Fs10706, and Fs13617 suppressed host immunity through two potential iron-binding sites conserved in CFEM family members, characterized by Asp and Phe residues in Fs08184, Fs10706, and Fs13617. Additionally, the Asp and Phe residues within the iron-chelating site were necessary for the iron acquisition of F. sacchari and contributed to creating low-free-iron conditions at the interface of plant and pathogen interactions. It appeared that F. sacchari might employ Asp-Phe-type CFEM members to influence host iron homeostasis to suppress host immunity and to facilitate its successful colonization.
Development and Validation of a Novel Four Gene-Pairs Signature for Predicting Prognosis in DLBCL Patients
Authors: Tanabe Atsushi , Ndzinu Jerry , Sahara Hiroeki
Published: November 2024

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin’s lymphoma. Because individual clinical outcomes of DLBCL in response to standard therapy differ widely, new treatment strategies are being investigated to improve therapeutic efficacy. In this study, we identified a novel signature for stratification of DLBCL useful for prognosis prediction and treatment selection. First, 408 prognostic gene sets were selected from approximately 2500 DLBCL samples in public databases, from which four gene-pair signatures consisting of seven prognostic genes were identified by Cox regression analysis. Then, the risk score was calculated based on these gene-pairs and we validated the risk score as a prognostic predictor for DLBCL patient outcomes. This risk score demonstrated independent predictive performance even when combined with other clinical parameters and molecular subtypes. Evaluating external DLBCL cohorts, we demonstrated that the risk-scoring model based the four gene-pair signatures leads to stable predictive performance, compared with nine existing predictive models. Finally, high-risk DLBCL showed high resistance to DNA damage caused by anticancer drugs, suggesting that this characteristic is responsible for the unfavorable prognosis of high-risk DLBCL patients. These results provide a novel index for classifying the biological characteristics of DLBCL and clearly indicate the importance of genetic analyses in the treatment of DLBCL.
Understanding Quorum-Sensing and Biofilm Forming in Anaerobic Bacterial Communities
Authors: Markowska Kinga , Szymanek-Majchrzak Ksenia , Pituch Hanna , Majewska Anna
Published: November 2024

Biofilms are complex, highly organized structures formed by microorganisms, with functional cell arrangements that allow for intricate communication. Severe clinical challenges occur when anaerobic bacterial species establish long-lasting infections, especially those involving biofilms. These infections can occur in device-related settings (e.g., implants) as well as in non-device-related conditions (e.g., inflammatory bowel disease). Within biofilms, bacterial cells communicate by producing and detecting extracellular signals, particularly through specific small signaling molecules known as autoinducers. These quorum-sensing signals are crucial in all steps of biofilm formation: initial adhesion, maturation, and dispersion, triggering gene expression that coordinates bacterial virulence factors, stimulates immune responses in host tissues, and contributes to antibiotic resistance development. Within anaerobic biofilms, bacteria communicate via quorum-sensing molecules such as N-Acyl homoserine lactones (AHLs), autoinducer-2 (AI-2), and antimicrobial molecules (autoinducing peptides, AIPs). To effectively combat pathogenic biofilms, understanding biofilm formation mechanisms and bacterial interactions is essential. The strategy to disrupt quorum sensing, termed quorum quenching, involves methods like inactivating or enzymatically degrading signaling molecules, competing with signaling molecules for binding sites, or noncompetitively binding to receptors, and blocking signal transduction pathways. In this review, we comprehensively analyzed the fundamental molecular mechanisms of quorum sensing in biofilms formed by anaerobic bacteria. We also highlight quorum quenching as a promising strategy to manage bacterial infections associated with anaerobic bacterial biofilms.
Metabolomic Hallmarks of Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease
Authors: Beyoğlu Diren , Popov Yury V. , Idle Jeffrey R.
Published: November 2024

From a detailed review of 90 experimental and clinical metabolomic investigations of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD), we have developed metabolomic hallmarks for both obesity and MASLD. Obesity studies were conducted in mice, rats, and humans, with consensus biomarker groups in plasma/serum being essential and nonessential amino acids, energy metabolites, gut microbiota metabolites, acylcarnitines and lysophosphatidylcholines (LPC), which formed the basis of the six metabolomic hallmarks of obesity. Additionally, mice and rats shared elevated cholesterol, humans and rats shared elevated fatty acids, and humans and mice shared elevated VLDL/LDL, bile acids and phosphatidylcholines (PC). MASLD metabolomic studies had been performed in mice, rats, hamsters, cows, geese, blunt snout breams, zebrafish, and humans, with the biomarker groups in agreement between experimental and clinical investigations being energy metabolites, essential and nonessential amino acids, fatty acids, and bile acids, which lay the foundation of the five metabolomic hallmarks of MASLD. Furthermore, the experimental group had higher LPC/PC and cholesteryl esters, and the clinical group had elevated acylcarnitines, lysophosphatidylethanolamines/phosphatidylethanolamines (LPE/PE), triglycerides/diglycerides, and gut microbiota metabolites. These metabolomic hallmarks aid in the understanding of the metabolic role played by obesity in MASLD development, inform mechanistic studies into underlying disease pathogenesis, and are critical for new metabolite-inspired therapies.
A Potential Use of Vidarabine: Alleviation of Functional Constipation Through Modulation of the Adenosine A2A Receptor-MLC Signaling Pathway and the Gut Microbiota
Authors: Gao Xiaoyu , Guo Kaifeng , Liu Shuangfeng , Yang Weixing , Sheng Jun , Tian Yang , Peng Lei , Zhao Yan
Published: November 2024

Vidarabine (VID) is an antiviral medication that is commonly utilized to treat conditions such as hand, foot, and mouth disease and herpes. Constipation is a prevalent complication of these diseases. Could VID treat these diseases by influencing defecation behavior? To date, no studies have been conducted on the potential of VID to relieve constipation. Therefore, a systematic investigation was conducted into the laxative effects and mechanisms of VID using loperamide-induced functional constipated mice. The findings indicate that the oral administration of VID promoted gastrointestinal peristalsis, improved fecal properties, facilitated defecation, and demonstrated a significant laxative effect on functional constipated mice. It has been demonstrated that VID may increase the water content of feces by regulating the expression of aquaporins (AQP3, AQP4, and AQP8) in the colon and promote intestinal motility by regulating the expression of neurotransmitters (AChE and VIP) and the adenosine A2A receptor–myosin light chain (A2AR-MLC) signaling pathway in constipated mice. Concurrently, VID may also reduce colonic inflammation in constipated mice, reinforce the gut barrier function, and alter the composition and structure of the gut microbial community. Some microbial taxa, including Firmicutes and Lactobacillus, were found to be associated with the alleviation of constipation, while other taxa, including Bacteroidetes, Proteobacteria, Muribaculaceae, Muribaculum, norank__f__Desulfovibrionaceae, and Parasutterella, were found to be associated with constipation. These results indicate that the gut microbiota may play a significant role in the alleviation of constipation by VID. These findings confirm the efficacy of VID in a constipated animal model, which justifies further investigation into its potential clinical applications.
Advanced SnO2 Thin Films: Stability and Sensitivity in CO Detection
Authors: Maksimova Nadezhda K. , Malinovskaya Tatiana D. , Zhek Valentina V. , Sergeychenko Nadezhda V. , Chernikov Evgeniy V. , Sokolov Denis V. , Koroleva Aleksandra V. , Sobolev Vitaly S. , Korusenko Petr M.
Published: November 2024

This paper presents the results of a study on the characteristics of semiconductor sensors based on thin SnO2 films modified with antimony, dysprosium, and silver impurities and dispersed double Pt/Pd catalysts deposited on the surface to detect carbon monoxide (CO). An original technology was developed, and ceramic targets were made from powders of Sn-Sb-O, Sn–Sb-Dy–O, and Sn–Sb-Dy-Ag–O systems synthesized by the sol–gel method. Films of complex composition were obtained by RF magnetron sputtering of the corresponding targets, followed by technological annealing at various temperatures. The morphology of the films, the elemental and chemical composition, and the electrical and gas-sensitive properties were studied. Special attention was paid to the effect of the film composition on the stability of sensor parameters during long-term tests under the influence of CO. It was found that different combinations of concentrations of antimony, dysprosium, and silver had a significant effect on the size and distribution of nanocrystallites, the porosity, and the defects of films. The mechanisms of degradation under prolonged exposure to CO were examined. It was established that Pt/Pd/SnO2:0.5 at.% Sb film with optimal crystallite sizes and reduced porosity provided increased stability of carbon monoxide sensor parameters, and the response to the action of 100 ppm carbon monoxide was G1/G0 = 2–2.5.
Okra WRKY Transcription Factor AeWRKY32 and AeWRKY70 Are Involved in Salt Stress Response
Authors: He Jiaojun , Chen Shutong , Chen Ru , Li Xinyu , Wu Jiahua , Zheng Yueping , Li Feifei , Zhan Yihua
Published: November 2024

Soil salinization is one of the abiotic stresses that inhibit plant growth and development, which seriously restricts global crop production. WRKY transcription factors play an important role in regulating plant responses to stress such as salt stress. In our previous study, two WRKY family genes from okra, AeWRKY32 and AeWRKY70, were significantly up-regulated and down-regulated, respectively, in response to salt stress. In this study, subcellular localization showed that they were localized to the nucleus. The down-regulation of AeWRKY32 and AeWRKY70 via whole plant virus-induced gene silencing (VIGS) increased and decreased plant sensitivity to salt stress, respectively. Ectopic expression of AeWRKY32 and AeWRKY70 led to promoted and reduced salt tolerance in transgenic Arabidopsis, respectively. There was no significant difference between transgenic plants and wild type (WT) without salt treatment. Salt stress significantly inhibited plant growth. The decrease of chlorophyll content and the increase of anthocyanin content in AeWRKY32-overexpressed transgenic plants were lower than those in the WT, while AeWRKY70-overexpressed plants had the opposite effect. Under salt stress, the AeWRKY70-overexpressed plants had the highest malondialdehyde (MDA) content, followed by the WT, and the lowest in AeWRKY32-overexpressed plants. The hydrogen peroxide (H2O2) content and superoxide anion (O2•−) generation rate were only slightly increased. Moreover, salt stress significantly increased plant proline content and antioxidant enzyme activities, which was highest in AeWRKY70-overexpressed plants except superoxide dismutase (SOD). Taken together, these results suggest that AeWRKY32 and AeWRKY70 play positive and negative roles in plant in response to salt stress, respectively.
Innovative Approaches to Fucoxanthin Delivery: Characterization and Bioavailability of Solid Lipid Nanoparticles with Eco-Friendly Ingredients and Enteric Coating
Authors: Ding Lijun , Luo Xiao , Xian Qingyue , Zhu Sishi , Wen Weijia
Published: November 2024

Fucoxanthin (FN), a carotenoid derived from brown seaweed and algae, offers significant health benefits. However, its unique structure leads to challenges in stability and bioavailability. To overcome these issues, we successfully encapsulated fucoxanthin in solid lipid nanoparticles (SLNs) utilizing health-safe materials, achieving remarkable results. SLNs exhibited a nanoscale size of 248.98 ± 4.0 nm, along with an impressive encapsulation efficiency of 98.30% ± 0.26% and a loading capacity of 5.48% ± 0.82% in lipid. The polydispersity index (PDI) was measured at 0.161 ± 0.03, indicating a narrow size distribution, while the high negative zeta potential of −32.93 ± 1.2 mV suggests excellent stability. Pharmacokinetic studies conducted in Sprague–Dawley rats revealed an exceptional oral bioavailability of 2723.16% compared to fucoxanthin crystals, likely attributed to the enhanced stability and improved cellular uptake of the SLNs. To further improve bioavailability, we creatively applied enteric coatings to the freeze-dried SLNs, effectively protecting fucoxanthin from gastric degradation, which is supported by in vitro digestion results. These findings underscore the potential of SLNs as a superior delivery system for fucoxanthin, significantly enhancing its therapeutic efficacy and broadening its application in the food and pharmaceutical industries.
Effects of Larch Woolly Adelgid Infestation on Morphological, Histological and Allelochemical Traits of European Larch Needles
Authors: Dancewicz Katarzyna , Kordan Bożena , Damszel Marta , Sergiel Iwona , Biesaga Magdalena , Mroczek Joanna , Gabryś Beata
Published: November 2024

The study was carried out to assess the effect of the larch wooly adelgid Adelges laricis Vallot (Hemiptera: Adelgidae) infestation on its secondary host, the European larch Larix decidua Mill. Morphology and anatomy of adelgid-infested needles, and content of defense phenolic compounds including individual flavonoids isorhamnetin, kaempferol, quercetin, rutin, catechin, epicatechin, apigenin, ampelopsin and taxifolin, were analyzed. The amount of total phenols in needles from adelgid-infested twigs of L. decidua increased following the development of the A. laricis population, from the end of April until the end of June. The most abundant among flavonoids were the flavanols, mainly catechin and epicatechin, which predominated in the larch needles during the whole period of adelgid infestation. The content of catechin and epicatechin increased following the increase in the adelgid population number. An increase in content occurred also in flavanonols ampelopsin and taxifolin, while the content of the flavonol kaempferol decreased as the population number of A. laricis increased. The analysis of the anatomical structure of needles showed changes in the shape of the needles, the presence of a thicker layer of epicuticular waxes, and a higher number of mesophyll layers as a result of adelgid feeding.
Glue and Ethanol Mixture for Aneurysm Endovascular Treatment: Animal Lab Study, Imaging, and Histopathological Findings
Authors: Muto Massimo , Leone Giuseppe , Giordano Flavio , Guarnieri Gianluigi , Di Donna Antonio , Andreone Vincenzo , Di Maro Eva , Poli Alessandro , Fonti Niccolò , Caranci Ferdinando , Muto Mario
Published: November 2024

Background: This study aims to investigate the degree of penetration, permanence of occlusion, and vascular changes induced by a newly modified mixture of n-butyl cyanoacrylate (Glubran 2®), ethanol, and Lipidol® (GEL) in the endovascular treatment of experimental aneurysms induced in swine. Methods: Bilateral pouch aneurysms were created in the wall of the internal carotid artery in eighteen pigs. The sixteen aneurysms were treated with a new mixture of GEL with different component proportions. Angiograms were obtained at the time of treatment and at 1, 4, and 16 weeks after treatment. According to the scheduled experimental design, subjects were sacrificed at the time of treatment and 7, 30, and 90 days after the embolization of experimentally induced aneurysms. The internal carotid artery and aneurysms were removed en bloc and sampled for histopathologic study. Results: The mixture induced complete and stable occlusion without recanalization in all experimentally induced aneurysms throughout the study period. Histopathological studies showed focal angionecrosis and acute inflammatory reactions from 7 dpi, followed by chronic inflammation and vessel wall thickening. Conclusions: The GEL mixture may be useful in future clinical applications for the embolization of arteriovenous malformations, the control of acute bleeding, and the isolation of aneurysms due to its very short polymerization time and minimal adhesion to the microcatheter.