bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell Wall Microdomains Analysis in the Quadrifids of Utricularia dichotoma
Authors: Płachno Bartosz J. , Kapusta Małgorzata , Feldo Marcin , Świątek Piotr
Published: January 2025

Carnivorous plants have fascinated botanists and ecologists with their various unusual adaptations in organ structure, physiology, and complex interactions with other organisms since the time of Charles Darwin. Species of the genus Utricularia (bladderworts, family Lentibulariaceae) are carnivorous plants that prey mainly on invertebrates using traps (bladders) of leaf origin. In the traps, there are glandular trichomes called quadrifids, which produce digestive enzymes and absorb the products of prey digestion. These quadrifids are unique due to their highly complex glandular cell structure; hence, they are an excellent model for studying the cell wall and its specialization. The main aim of the study was to investigate the presence and distribution of homogalacturonans (HGs) and hemicelluloses in the cell walls of trichome cells and especially in cell wall ingrowths in the quadrifid cells. The following antibodies were used against the wall components: anti-HGs (homogalacturonans) —JIM5 (low methylesterified HGs), JIM7 (highly esterified HGs), LM19 (low methylesterified HGs), CCRC-M38 (a fully de-esterified HG), LM5 (galactan); anti-hemicelluloses—LM25 (galactoxyloglucan; XXLLG, XXLG, XXXG modules of xyloglucans), LM15 (xyloglucan), CCRC-M138 (xylan), LM11 (heteroxylan); and anti-mannans: LM20 (heteromannan) and LM22 (heteromannan). The localization of the examined compounds was determined using immunohistochemistry techniques and immunogold labeling. In quadrifid cells, we found differences in the presence of the epitope detected by the LM5 antibody in the cell walls. In addition, cell wall ingrowths represented distinct microdomains of the cell wall in terms of the occurrence of wall components (they were methylesterified and demethylesterified homogalacturonan-poor). Hemicelluloses (galactoxyloglucan and xyloglucan) and arabinogalactans co-occur in cell wall ingrowths. Also, a part of the cell wall of the pedestal cell, which forms a Casparian strip, represented a distinct microdomain. We did not detect epitopes recognized by LM11, LM20 and LM22 antibodies. Our research shows that several cell wall microdomains occur in the cell walls of quadrifid cells. They differ depending on the presence and distribution of low methylesterified HGs, highly esterified HGs, fully de-esterified HGs, galactan (the epitope detected by the LM5 antibody), xyloglucan, galactoxyloglucan, and xylan (the epitope detected by the CCRC-M138 antibody).
MK-8776 and Olaparib Combination Acts Synergistically in Hepatocellular Carcinoma Cells, Demonstrating Lack of Adverse Effects on Liver Tissues in Ovarian Cancer PDX Model
Authors: Bębenek Wiktoria , Gajek Arkadiusz , Marczak Agnieszka , Malý Jan , Smejkal Jiří , Statkiewicz Małgorzata , Rusetska Natalia , Bryś Magdalena , Rogalska Aneta
Published: January 2025

Hepatocellular carcinoma (HCC) cells critically depend on PARP1 and CHK1 activation for survival. Combining the PARP inhibitor (PARPi) olaparib with a CHK1 inhibitor (MK-8776, CHK1i) produced a synergistic effect, reducing cell viability and inducing marked oxidative stress and DNA damage, particularly in the HepG2 cells. This dual treatment significantly increased apoptosis markers, including γH2AX and caspase-3/7 activity. Both HCC cell lines exhibited heightened sensitivity to the combined treatment. The effect of drugs on the expression of proliferation markers in an olaparib-resistant patient-derived xenograft (PDX) model of ovarian cancer was also investigated. Ovarian tumors displayed reduced tissue growth, as reflected by a drop in proliferation marker Ki-67 levels in response to PARPi combined with CHK1i. No changes were observed in corresponding liver tissues using Ki-67 and pCHK staining, which indicates the absence of metastases and a hepatotoxic effect. Thus, our results indicate that the dual inhibition of PARP and CHK1 may prove to be a promising therapeutic approach in the treatment of primary HCC as well as OC tumors without the risk of liver metastases, especially in patients with olaparib-resistant tumor profiles.
Pathophysiology of Group 3 Pulmonary Hypertension Associated with Lung Diseases and/or Hypoxia
Authors: Nakamura Kazufumi , Akagi Satoshi , Ejiri Kentaro , Taya Satoshi , Saito Yukihiro , Kuroda Kazuhiro , Takaya Yoichi , Toh Norihisa , Nakayama Rie , Katanosaka Yuki , Yuasa Shinsuke
Published: January 2025

Pulmonary hypertension associated with lung diseases and/or hypoxia is classified as group 3 in the clinical classification of pulmonary hypertension. The efficacy of existing selective pulmonary vasodilators for group 3 pulmonary hypertension is still unknown, and it is currently associated with a poor prognosis. The mechanisms by which pulmonary hypertension occurs include hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, a decrease in pulmonary vascular beds, endothelial dysfunction, endothelial-to-mesenchymal transition, mitochondrial dysfunction, oxidative stress, hypoxia-inducible factors (HIFs), inflammation, microRNA, and genetic predisposition. Among these, hypoxic pulmonary vasoconstriction and subsequent pulmonary vascular remodeling are characteristic factors involving the pulmonary vasculature and are the focus of this review. Several factors have been reported to mediate vascular remodeling induced by hypoxic pulmonary vasoconstriction, such as HIF-1α and mechanosensors, including TRP channels. New therapies that target novel molecules, such as mechanoreceptors, to inhibit vascular remodeling are awaited.
Identification of HXK Gene Family and Expression Analysis of Salt Tolerance in Buchloe dactyloides
Authors: Qi Haole , Wang Sining , Liu Yuehan , Wang Xueping , Li Xiaoxia , Shi Fengling
Published: January 2025

Buchloe dactyloides is one of the typical ecological grass species, characterized by its strong salt tolerance. Hexokinase (HXK) plays a crucial role in plant growth, development, and resistance to abiotic stresses. To understand the function of HXKs in the salt tolerance of B. dactyloides, this study identified and analyzed the HXK gene family members using the whole-genome data of B. dactyloides. Additionally, transcriptomic methods were employed to investigate the expression levels and stress response patterns of the HXK family genes under salt stress. The results showed that 25 HXK genes were identified in the B. dactyloides HXK gene family, which were classified into three subfamilies based on the phylogenetic tree. Members within the same subfamily exhibited similar gene structures and conserved motifs. The promoter regions of BdHXKs contained numerous cis-regulatory elements associated with plant hormone responses, plant growth and development, and resistance to abiotic stresses. Quantitative real-time PCR analysis provided preliminary evidence that the BdHXK5, BdHXK7, and BdHXK23 genes might play important roles in the salt tolerance regulation of B. dactyloides. These findings offer a theoretical foundation for further elucidating the functions and molecular regulatory mechanisms of BdHXKs under salt stress. This study has provided a theoretical basis for the breeding of new varieties of ecological restoration grasses with stronger salt tolerance and better growth and development. This is of great significance for the improvement and ecological restoration of saline–alkali land.
Insulin Receptor Substrate-2 Regulates the Secretion of Growth Factors in Response to Amino Acid Deprivation
Authors: Takahashi Ayaka , Furuta Haruka , Nishi Hiroki , Kamei Hiroyasu , Takahashi Shin-Ichiro , Hakuno Fumihiko
Published: January 2025

Insulin receptor substrates (IRSs) are well-known mediators of the insulin and insulin-like growth factor (IGF)-I signaling pathways. We previously reported that the protein levels of IRS-2, a molecular species of IRS, were upregulated in the livers of rats fed a protein-restricted diet. This study aimed to elucidate the physiological role of IRS-2, whose level increases in response to protein restriction in cultured hepatocyte models. Hepatocyte-derived cell lines subjected to amino acid deprivation showed increased IRS2 mRNA and IRS-2 protein levels due to increased IRS2 transcription and translation, respectively. Amino acid deprivation markedly increased vascular endothelial growth factor-D (VEGF-D) secretion. Remarkably, the amino acid deprivation-induced VEGF-D secretion was suppressed by IRS-2 knockdown and enhanced by IRS-2 overexpression. These results suggest that IRS-2 is an intercellular signaling molecule that extracellularly transmits information on amino acid deprivation stress by regulating the secretion of growth factors such as VEGF-D. Moreover, this function of IRS-2 is distinct from its currently accepted function as a mediator of the insulin/IGF-I signaling pathways. This study demonstrates that IRS-2 can modulate protein secretion in an insulin-independent manner and greatly expands our understanding of the role of IRS-2, which is upregulated in response to amino acid deprivation.
An Evaluation of the Safety of Intravenous Injections of the Natural Extracellular Hemoglobin M101 in Dogs and Monkeys
Authors: Leize-Zal Elisabeth , Demini Leïla , Barrou Benoît , Zal Franck
Published: January 2025

Hemoglobin-based oxygen carriers have been developed to compensate the needs of blood for transfusions. Most of them were based on intracellular hemoglobin extracted from bovine or human blood, but unfortunately, this type of hemoglobin did not pass through the last steps of clinical trials. In this context, HEMARINA discovered a natural extracellular hemoglobin, possessing several advantages avoiding intracellular hemoglobin-related side effects. Many preclinical studies assessed the safety of M101 used in intravenous (IV) injection in rodents. To explore the safety of IV injections of M101 in large mammals, six dogs received each a single injection of liquid M101 according to a dose escalation with a 48 h follow-up. Then, two monkeys received multiple IV injections of the same dose of M101 every hour for seven hours. This study showed that single and multiple IV injections in dogs and monkeys did not cause clinical or histological lesions, nor did they induce immunological reactions. This makes M101 the best candidate to date for human use in emergency situations requiring blood and, in several diseases, causing hypoxia problems.
Genome-Wide Analysis of bZIP Transcription Factors and Expression Patterns in Response to Salt and Drought Stress in Vaccinium corymbosum
Authors: Feng Xinghua , Wang Chuchu , Jia Sijin , Wang Jiaying , Zhou Lianxia , Song Yan , Guo Qingxun , Zhang Chunyu
Published: January 2025

The basic leucine zipper (bZIP) transcription factors play essential roles in multiple stress responses and have been identified and functionally characterized in many plant species. However, the bZIP family members in blueberry are unclear. In this study, we identified 102 VcbZIP genes in Vaccinium corymbosum. VcbZIPs were divided into 10 groups based on phylogenetic analysis, and each group shared similar motifs, domains, and gene structures. Predictions of cis-regulatory elements in the upstream sequences of VcbZIP genes indicated that VcbZIP proteins are likely involved in phytohormone signaling pathways and abiotic stress responses. Analyses of RNA deep sequencing data showed that 18, 13, and 7 VcbZIP genes were differentially expressed in response to salt, drought, and ABA stress, respectively, for the blueberry cultivar Northland. Ten VcbZIP genes responded to both salt and drought stress, indicating that salt and drought have unique and overlapping signals. Of these genes, VcbZIP1–3 are responsive to salt, drought, and abscisic acid treatments, and their encoded proteins may integrate salt, drought, and ABA signaling. Furthermore, VcbZIP1–3 from group A and VcbZIP83–84 and VcbZIP75 from group S exhibited high or low expression under salt or drought stress and might be important regulators for improving drought or salt tolerance. Pearson correlation analyses revealed that VcbZIP transcription factors may regulate stress-responsive genes to improve drought or salt tolerance in a functionally redundant manner. Our study provides a useful reference for functional analyses of VcbZIP genes and for improving salt and drought stress tolerance in blueberry.
Alcohol Consumption and Autoimmune Diseases
Authors: Terracina Sergio , Caronti Brunella , Lucarelli Marco , Francati Silvia , Piccioni Maria Grazia , Tarani Luigi , Ceccanti Mauro , Caserta Micaela , Verdone Loredana , Venditti Sabrina , Fiore Marco , Ferraguti Giampiero
Published: January 2025

Alcohol is the second-most misused substance after tobacco. It has been identified as a causal factor in more than 200 diseases and 5.3% of all deaths and is associated with significant behavioral, social, and economic difficulties. As alcohol consumption may modulate the immune system’s regulatory mechanisms to avoid attacking the body’s tissues, it has been proven to play a dichotomic role in autoimmune diseases (ADs) based on the quantity of consumption. In this review, we report updated evidence on the role of alcohol in ADs, with a focus on alcohol addiction and the human biological immune system and the relationship between them, with alcohol as a risk or protective factor. Then, in this narrative review, we report the main evidence on the most studied ADs where alcohol represents a key modulator, including autoimmune thyroiditis, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, diabetes, allergic rhinitis, and primary biliary cholangitis. Alcohol at low–moderate dosages seems mostly to have a protective role in these diseases, while at higher dosages, the collateral risks surpass possible benefits. The specific mechanisms by which low-to-moderate alcohol intake relieves AD symptoms are not yet fully understood; however, emerging studies suggest that alcohol may have a systemic immunomodulatory effect, potentially altering the balance of anti-inflammatory innate and adaptive immune cells, as well as cytokines (via the NF-κB or NLRP3 pathways). It might influence the composition of the gut microbiome (increasing amounts of beneficial gut microbes) and the production of their fatty acid metabolites, such as short-chain fatty acids (SCFAs) and polyunsaturated fatty acids (PUFAs), as well as elevated concentrations of acetate, high-density lipoprotein (HDL), and nitric oxide (NO). Unfortunately, a definite acceptable daily intake (ADI) of ethanol is complicated to establish because of the many mechanisms associated with alcohol consumption such that despite the interesting content of these findings, there is a limit to their applicability and risks should be weighed in cases of alcoholic drinking recommendations. The aim of future studies should be to modulate those beneficial pathways involved in the alcohol-protective role of ADs with various strategies to avoid the risks associated with alcohol intake.
Establishment of iPSC-Derived MSCs Expressing hsa-miR-4662a-5p for Enhanced Immune Modulation in Graft-Versus-Host Disease (GVHD)
Authors: Lee Susie , Kim Eung-Won , Lee Hae-Ri , Lim Sun-Ung , Jung Chan Kwon , Kang Young-Ju , Jung Gyung-Ah , Oh Il-Hoan
Published: January 2025

The immune-modulatory effects of mesenchymal stromal cells (MSCs) are widely used to treat inflammatory disorders, with indoleamine 2,4-dioxygenase-1 (IDO-1) playing a pivotal role in suppressing stimulated T-cell proliferation. Taking that three-dimensional (3D) cultures enhance MSCs’ anti-inflammatory properties compared with two-dimensional (2D) cultures, the differentially expressed miRNAs were examined. Thus, we identified hsa-miR-4662a-5p (miR-4662a) as a key inducer of IDO-1 via its suppression of bridging integrator-1 (BIN-1), a negative regulator of the IDO-1 gene. The IDO-1-inducing potential of miR-4662a was conserved across primary MSCs from various donors and sources but exhibited variability. Notably, iPSC-derived MSCs (iMSCs) demonstrated superior IDO-1 induction and immune-modulatory efficacy compared with their donor-matched primary MSCs. Accordingly, iMSCs expressing miR-4662a (4662a/iMSC) exhibited stronger suppressive effects on T-cell proliferation and more potent suppressive effects on graft-versus-host disease (GVHD), improving survival rates and reducing tissue damage in the liver and gut. Our results point to the therapeutic potential of standardized, off-the-shelf 4662a/iMSC as a robust immune-modulating cell therapy for GVHD.
One-Step Fabrication of Water-Dispersible Calcium Phosphate Nanoparticles with Immobilized Lactoferrin for Intraoral Disinfection
Authors: Nakamura Maki , Oyane Ayako , Inose Tomoya , Kanemoto Yukimi , Miyaji Hirofumi
Published: January 2025

Lactoferrin is a highly safe antibacterial protein found in the human body and in foods. Calcium phosphate (CaP) nanoparticles with immobilized lactoferrin could therefore be useful as intraoral disinfectants for the prevention and treatment of dental infections because CaP is a mineral component of human teeth. In this study, we fabricated CaP nanoparticles with co-immobilized lactoferrin and heparin using a simple one-step coprecipitation process. Heparin, a negatively charged polysaccharide, was used as both an immobilizing agent for lactoferrin and a particle-dispersing agent. The immobilization efficiency for lactoferrin in the CaP nanoparticles depended on the concentrations of both the lactoferrin and heparin in the reaction solution and was over 90% under optimal conditions. The nanoparticles had a hydrodynamic diameter of about 150–200 nm and could be well dispersed in water, owing to their relatively large negative zeta potential derived from heparin. They were found to exhibit antibacterial activity against Actinomyces naeslundii, which is involved in the initial formation of dental plaque that consequently leads to dental caries and periodontal disease. These results indicate the potential of the proposed nanoparticles as intraoral disinfectants.
Application of Synthetic Microbial Communities of Kalidium schrenkianum in Enhancing Wheat Salt Stress Tolerance
Authors: Zhu Jing , Jia Qiong , Tang Qi-Yong , Osman Ghenijan , Gu Mei-Ying , Wang Ning , Zhang Zhi-Dong
Published: January 2025

Soil salinization poses a significant challenge to global agriculture, particularly in arid and semi-arid regions like Xinjiang. Kalidium schrenkianum, a halophytic plant adapted to saline-alkaline conditions, harbors endophytic microorganisms with potential plant growth-promoting properties. In this study, 177 endophytic bacterial strains were isolated from K. schrenkianum, and 11 key strains were identified through functional screening based on salt tolerance, nutrient solubilization, and growth-promoting traits. Synthetic microbial communities (SMCs) were then constructed using these strains and optimized to enhance wheat growth under salt stress. The SMCs significantly improved seed germination, root length, and seedling vigor in both spring and winter wheat in hydroponic and pot experiments. Furthermore, the SMCs enhanced the activities of antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and levels of malondialdehyde (MDA) and proline (PRO). They also reduced oxidative stress and improved chlorophyll content in wheat seedlings. These results demonstrate the potential of microbial consortia derived from extreme environments as eco-friendly biofertilizers for improving crop performance in saline soils, offering a sustainable alternative to chemical fertilizers and contributing to agricultural resilience and productivity.
Detection of Circulating Tumor DNA in Liquid Biopsy: Current Techniques and Potential Applications in Melanoma
Authors: Martínez-Vila Clara , Teixido Cristina , Aya Francisco , Martín Roberto , González-Navarro Europa Azucena , Alos Llucia , Castrejon Natalia , Arance Ana
Published: January 2025

The treatment landscape for advanced melanoma has transformed significantly with the advent of BRAF and MEK inhibitors (BRAF/MEKi) targeting BRAFV600 mutations, as well as immune checkpoint inhibitors (ICI) like anti-PD-1 monotherapy or its combinations with anti-CTLA-4 or anti-LAG-3. Despite that, many patients still do not benefit from these treatments at all or develop resistance mechanisms. Therefore, prognostic and predictive biomarkers are needed to identify patients who should switch or escalate their treatment strategies or initiate an intensive follow-up. In melanoma, liquid biopsy has shown promising results, with a potential role in predicting relapse in resected high-risk patients or in disease monitoring during the treatment of advanced disease. Several components in peripheral blood have been analyzed, such as circulating tumor cells (CTCs), cell-free DNA (cfDNA), and circulant tumoral DNA (ctDNA), which have turned out to be particularly promising. To analyze ctDNA in blood, different techniques have proven to be useful, including digital droplet polymerase chain reaction (ddPCR) to detect specific mutations and, more recently, next-generation sequencing (NGS) techniques, which allow analyzing a broader repertoire of the mutation landscape of each patient. In this review, our goal is to update the current understanding of liquid biopsy, focusing on the use of ctDNA as a biological material in the daily clinical management of melanoma patients, in particular those with advanced disease treated with ICI.
Adipose-Derived Stromal Cells Exposed to RGD Motifs Enter an Angiogenic Stage Regulating Endothelial Cells
Authors: Brembilla Nicolo-Constantino , El-Harane Sanae , Durual Stéphane , Krause Karl-Heinz , Preynat-Seauve Olivier
Published: January 2025

Adipose-derived stromal cells (ASCs) possess significant regenerative potential, playing a key role in tissue repair and angiogenesis. During wound healing, ASC interacts with the extracellular matrix by recognizing arginylglycylaspartic acid (RGD) motifs, which are crucial for mediating these functions. This study investigates how RGD exposure influences ASC behavior, with a focus on angiogenesis. To mimic the wound-healing environment, ASC were cultured in a porcine gelatin sponge, an RGD-exposing matrix. Transcriptomics revealed that ASC cultured in gelatin exhibited an upregulated expression of genes associated with inflammation, angiogenesis, and tissue repair compared to ASC in suspension. Pro-inflammatory and pro-angiogenic factors, including IL-1, IL-6, IL-8, and VEGF, were significantly elevated. Functional assays further demonstrated that ASC-conditioned media enhanced endothelial cell migration, tubulogenesis, and reduced endothelial permeability, all critical processes in angiogenesis. Notably, ASC-conditioned media also promoted vasculogenesis in human vascular organoids. The inhibition of ASC-RGD interactions using the cyclic peptide cilengitide reversed these effects, underscoring the essential role of RGD-integrin interactions in ASC-mediated angiogenesis. These findings suggest that gelatin sponges enhance ASC’s regenerative and angiogenic properties via RGD-dependent mechanisms, offering promising therapeutic potential for tissue repair and vascular regeneration. Understanding how RGD modulates ASC behavior provides valuable insights into advancing cell-based regenerative therapies.
Haematological Manifestations of SARS-CoV-2: Insights into Erythropoiesis, Hepcidin Regulation, and Cytokine Storm
Authors: Parham Elahi , Ahmad Makky , Falasca Marco
Published: January 2025

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a respiratory disease that can range in presentation from mild symptoms to severe conditions such as pneumonia and acute respiratory distress syndrome. SARS-CoV-2, a single-stranded RNA virus, spreads through aerosols and respiratory droplets. It enters human cells by binding to the angiotensin-converting enzyme 2 receptor, leading to various complications, including significant alterations in red blood cells and potential disruptions in haemoglobin function and oxygen transport. During infection, the interaction between hypoxia, inflammation, and haematopoiesis affects erythropoiesis at multiple levels. Hypoxia and inflammation, resulting from lung complications and a reduced red blood cell count, influence the regulation of hepcidin, a key regulator of iron levels in the blood. Elevated hepcidin levels are associated with hypoxia and the suppression of erythroferrone, a hormone that normally inhibits hepcidin production. Despite high levels of inflammation, patients in intensive care units often exhibit elevated ferritin levels, which, rather than indicating low hepcidin, suggest disrupted iron metabolism and the development of severe anaemia. Iron is kept in stores, likely due to paradoxically high hepcidin levels, which explains the elevated ferritin measurements. An increase in immature blood cells and a decrease in CD71+ erythroid cells are observed. The elevated levels of CD71+ erythroid cells highlight their dual role in modulating hyper-inflammation and immune response during disease progression. This review examines the pathway by which SARS-CoV-2 affects red blood cell production and the haematopoietic system and how it triggers cytokine storms through interleukins, immature blood cells, and CD71+ erythroid cells. Understanding these processes provides novel pathways for managing haematological manifestations and immune responses in patients with COVID-19.
Calcium Enhances the Effectiveness of Melatonin in Improving Nutritional Properties of Soybean Sprouts and Germination Under Salt and Cadmium Stress
Authors: Adhikari Arjun , Sapkota Mahesh , Savidya Raddella Nishani , Tosin Ajayi Tolulope , Adam Muchanji , Alam Mohammad Naushad , Kwon Eun-Hae , Kang Sang-Mo , Shaffique Shifa , Lee In-Jung
Published: January 2025

Salinity and cadmium exposure to agrarian land lowers crop yield and imposes toxicity in the food chain, ultimately affecting sustainable agriculture. Melatonin (Mel) and calcium (Ca) have been reported as potent regulators of plant growth and stress resistance. Based on this scenario, this study investigated the sole and combined effects of Mel and Ca on improving the antioxidant properties, mineral content, germination of sprout, and stress tolerance of soybean seedlings under salt and cadmium (Cd) stress. Optimal doses of 20 µM Mel and 1 mM Ca were identified to enhance sprout quality and seed germination. Treatments with Mel > 20 µM inhibited germination, while the combination of Mel (20 µM) and Ca (1 mM) significantly improved germination, mineral content (Ca, P, K), and antioxidant properties, including DPPH(2,2-Diphenyl-1-picrylhydrazyl) activity, polyphenols, flavonoids, and superoxide dismutase (SOD) activity. However, melatonin > 50 µM could completely cease the sprouting, whereas a Ca concentration of up to 10 mM was observed to be normal in sprouting. Additionally, this combination reduced malondialdehyde (MDA) levels and enhanced the proline, indicating decreased oxidative stress in soybean seedlings under stress conditions. Among various treatments tested, the Mel-Ca combination was most effective in enhancing sprout biomass, antioxidant activity, and seed viability under Salt+Cd stress. These findings underscore the synergistic role of Ca in optimizing melatonin pretreatment for stress mitigation in soybean seeds and also address the precaution for a possible negative impact of melatonin effects.
Improvement of Mutant Galactose-1-Phosphate Uridylyltransferase (GALT) Activity by FDA-Approved Pharmacochaperones: A Preliminary Study
Authors: Scafuri Bernardina , Piscosquito Stefania , Giliberti Giulia , Facchiano Angelo , Miner Jaden , Balakrishnan Bijina , Lai Kent , Marabotti Anna
Published: January 2025

Classic galactosemia is a rare disease with long-term consequences that seriously affect the quality of life of patients. To date, various therapeutic approaches are being developed, but treatments that target the molecular defects in the mutant galactose-1-phosphate uridylyltransferase (GALT) gene are lacking. We conducted a computational search for putative pharmacochaperones by applying a drug repurposing strategy, and we found that one compound, already active as a pharmacochaperone in another pathology, doubled the enzymatic activity of the purified mutant enzyme in an in vitro test. Furthermore, an extensive computational search in a database of known active molecules found another compound able in its turn to improve in vitro enzymatic activity. Both compounds are predicted to interact with a cavity at the enzyme interface previously supposed to be an allosteric site for the GALT enzyme. In vitro tests confirmed also the reduced accumulation of galactose-1-phosphate (G1P) in fibroblasts of patients. Although these results must be considered preliminary, our findings pave the way for future research lines focused on the search for promising pharmacochaperones that can directly rescue the activity of the enzyme.
Aluminum-Nitride-Based Semiconductors: Growth Processes, Ferroelectric Properties, and Performance Enhancements
Authors: Wang Luyi , Cheng Jinhong , Qu Ke , Zhu Qingfeng , Tian Bobo , Yang Zhenzhong
Published: January 2025

Aluminum nitride (AlN)-based ferroelectric films offer significant advantages, including compatibility with CMOS back-end processes, potential for sustainable miniaturization, and intrinsic stability in the ferroelectric phase. As promising emerging materials, they have attracted considerable attention for their broad application potential in nonvolatile ferroelectric memories. However, several key scientific and technological challenges remain, including the preparation of single-crystal materials, epitaxial growth, and doping, which hinder their progress in critical ferroelectric devices. To accelerate their development, further research is needed to elucidate the underlying physical mechanisms, such as growth dynamics and ferroelectric properties. This paper provides a comprehensive review of the preparation methods of AlN-based ferroelectric films, covering AlN, Al1−xScxN, Al1−xBxN, YxAl1−xN, and ScxAlyGa1−x−yN. We systematically analyze the similarities, differences, advantages, and limitations of various growth techniques. Furthermore, the ferroelectric properties of AlN and its doped variants are summarized and compared. Strategies for enhancing the ferroelectric performance of AlN-based films are discussed, with a focus on coercive field regulation under stress, suppression of leakage current, fatigue mechanism, and long-term stability. Then, a brief overview of the wide range of applications of AlN-based thin films in electronic and photonic devices is presented. Finally, the challenges associated with the commercialization of AlN-based ferroelectrics are presented, and critical issues for future research are outlined. By synthesizing insights on growth methods, ferroelectric properties, enhancement strategies, and applications, this review aims to facilitate the advancement and practical application of AlN-based ferroelectric materials and devices.
Ontogeny of Fetal Cardiometabolic Pathways: The Potential Role of Cortisol and Thyroid Hormones in Driving the Transition from Preterm to Near-Term Heart Development in Sheep
Authors: Amanollahi Reza , Holman Stacey L. , Bertossa Melanie R. , Meakin Ashley S. , Thornburg Kent L. , McMillen I. Caroline , Wiese Michael D. , Lock Mitchell C. , Morrison Janna L.
Published: January 2025

Understanding hormonal and molecular changes during the transition from preterm to near-term gestation is essential for investigating how pregnancy complications impact fetal heart development and contribute to long-term cardiovascular risks for offspring. This study examines these cardiac changes in fetal sheep, focusing on the changes between 116 days (preterm) and 140 days (near term) of gestation (dG, term = 150) using Western blotting, LC-MS/MS, and histological techniques. We observed a strong correlation between cortisol and T3 (Triiodothyronine) in heart tissue in near-term fetuses, highlighting the role of glucocorticoid signalling in fetal heart maturation. Protein expression patterns in the heart revealed a decrease in multiple glucocorticoid receptor isoforms (GRα-A, GR-P, GR-A, GRα-D2, and GRα-D3), alongside a decrease in IGF-1R (a marker of cardiac proliferative capacity) and p-FOXO1(Thr24) but an increase in PCNA (a marker of DNA replication), indicating a shift towards cardiomyocyte maturation from preterm to near term. The increased expression of proteins regulating mitochondrial biogenesis and OXPHOS complex 4 reflects the known transition from glycolysis to oxidative phosphorylation, essential for meeting the energy demands of the postnatal heart. We also found altered glucose transporter expression, with increased pIRS-1(ser789) and GLUT-4 but decreased GLUT-1 expression, suggesting improved insulin responsiveness as the heart approaches term. Notably, the reduced protein abundance of SIRT-1 and SERCA2, along with increased phosphorylation of cardiac Troponin I(Ser23/24), indicates adaptations for more energy-efficient contraction in the near-term heart. In conclusion, these findings show the complex interplay of hormonal, metabolic, and growth changes that regulate fetal heart development, providing new insights into heart development that are crucial for understanding pathological conditions at birth and throughout life.
A Case of Diabetic Ischemic Ulcer with Toe Deformity Successfully Treated with Revascularization and Surgical Offloading
Authors: Nagasaki Kazuhito , Kikuchi Kyota , Tomita Masuomi , Hisamichi Katsuya , Izumi Yuko
Published: January 2025

Background: Diabetic ischemic ulcers with toe deformities are challenging to manage due to combined ischemia, infection, and mechanical stress. This case report highlights the successful treatment of a complex diabetic ischemic ulcer using a multidisciplinary approach that included revascularization and surgical offloading. Case Presentation: A 70-year-old male with type 2 diabetes mellitus presented with non-healing ulcers on the right third toe. The ulcers, located at the dorsal PIP joint and plantar MTP joint, were attributed to ischemia, infection, and progressive toe deformity. Angiography revealed significant arterial stenosis, which was treated with percutaneous transluminal angioplasty (PTA) to restore in-line flow and improve skin perfusion pressure. Surgical offloading included PIP resection arthroplasty and metatarsal shortening osteotomy. Postoperative management ensured complete ulcer healing, and no recurrence was observed during the three-year follow-up. Discussion: This case underscores the importance of combining revascularization to improve perfusion and surgical offloading to alleviate mechanical stress. Key factors for success included the restoration of in-line flow, achieving sufficient skin perfusion pressure, and reducing plantar pressure. Multidisciplinary collaboration among vascular surgeons, orthopedists, and wound care specialists played a critical role in achieving excellent long-term outcomes. Conclusions: Revascularization followed by surgical offloading provided effective treatment for a diabetic ischemic ulcer with toe deformity. This multidisciplinary approach demonstrates the necessity of individualized strategies to manage complex diabetic foot cases and prevent recurrence.
Future Directions in Diabetic Retinopathy Treatment: Stem Cell Therapy, Nanotechnology, and PPARα Modulation
Authors: Kąpa Maria , Koryciarz Iga , Kustosik Natalia , Jurowski Piotr , Pniakowska Zofia
Published: January 2025

This narrative review focuses on innovative treatment approaches to diabetic retinopathy to meet the urgent demand for advancements in managing both the early and late stages of the disease. Recent studies highlight the potential of adipose stem cells and their secreted factors in mitigating the retinal complications of diabetes, with promising results in improving visual acuity and reducing inflammation and angiogenesis in diabetic retinopathy. However, caution is warranted regarding the safety and long-term therapeutic effects of adipose stem cells transplantation. Bone marrow mesenchymal stem cells can also mitigate retinal damage in diabetic retinopathy. Studies demonstrate that bone marrow mesenchymal stem cells-derived exosomes can suppress the Wnt/β-catenin pathway, reducing oxidative stress, inflammation, and angiogenesis in the diabetic retina, offering promise for future diabetic retinopathy treatments. Nanotechnology has the ability to precisely target the retina and minimize systemic side effects. Nanoparticles and nanocarriers offer improved bioavailability, sustained release of therapeutics, and potential for synergistic effects. They can be a new way of effective treatment and prevention of diabetic retinopathy. Activation and modulation of PPARα as a means for diabetic retinopathy treatment has been widely investigated in recent years and demonstrated promising effects in clinical trials. PPARα activation turned out to be a promising therapeutic method for treating dyslipidemia, inflammation, and insulin sensitivity. The combination of PPARα modulators with small molecules offers an interesting perspective for retinal diseases’ therapy.
Characterization of Fitness Profiles in Youth Soccer Players in Response to Playing Roles Through Principal Component Analysis
Authors: Becerra Patiño Boryi A. , Montenegro Bonilla Aura D. , Paucar-Uribe Juan D. , Rada-Perdigón Diego A. , Olivares-Arancibia Jorge , Yáñez-Sepúlveda Rodrigo , López-Gil José Francisco , Pino-Ortega José
Published: January 2025

Background/Objectives: Physical fitness in youth soccer impacts individual and team performance through the specific demands that must be met on the field. Therefore, this study aimed to characterize and identify youth soccer players with regard to the roles they play on the field. Material and Methods: A cross-sectional study was designed to characterize and identify the physical fitness levels of youth soccer players using previously validated measurement tests. A total of 36 players were evaluated (15 defenders and 24 attackers) using various physical fitness tests: Squat Jump (SJ), Countermovement Jump (CMJ), Single-leg Countermovement Jumps (SLCMJs), COD-Timer 5-0-5, Speed (5, 10, 15, and 20 m), Yo-Yo Intermittent Recovery Test Level I (YYIR1), and Running-Based Anaerobic Sprint Test (RAST). The data were confirmed using the Shapiro–Wilk test. Effect sizes were obtained using the Rank-Biserial coefficient, and, to identify the profiles of attackers and defenders, principal component analysis (PCA) was employed. Results: For the strength variables, attackers obtained better results than defenders in the variable flight time in the SJ (p = 0.03; R-b = −0.33) and contact time (%) in the SLCMJ test (p = 0.04; R-b = −0.33). Meanwhile, defenders achieved better results than attackers in the SLCMJ test for the variable flight time (%) (p = 0.01; R-b = 0.33) and breaking angle (A°) in the Nordic Hamstring (p = 0.01; R-b = 0.33). The results showed differences according to the players’ roles. Three principal components were identified for both attackers and defenders. The PC1 for attackers considered variables of strength, asymmetry, change of direction, and power. PC2 only considered strength and power variables. PC3 considered variables of strength, speed, endurance, and power. For defenders, PC1 considered strength, asymmetry, and power. PC2 analyzed variables of strength, asymmetry, change of direction and power. Finally, PC3 only grouped speed variables. Conclusions: Although youth soccer positions involve offensive and defensive roles, this study reveals differences in certain physical fitness variables. Therefore, it is necessary to tailor training tasks according to the specificity of the playing position, in line with the systems of play used and the predominance of the role that players occupy, whether in defense or attack.
Effects of Combined Vibration Ergometry and Botulinum Toxin on Gait Improvement in Asymmetric Lower Limb Spasticity: A Pilot Study
Authors: Hefter Harald , Rosenthal Dietmar , Samadzadeh Sara
Published: January 2025

Objective: Botulinum neurotoxin type A (BoNT/A) injections and the new vibration ergometry training (VET) are studied for their combined effect on improving functional mobility in patients with asymmetric lower limb spasticity. Method: Gait was analyzed using the Infotronic® system, which measures ground reaction forces and foot contact patterns by means of special force-sensitive shoes strapped over feet or street shoes. Gait was measured several times, depending on the protocol patients underwent. Seven patients with asymmetric lower limb spasticity were analyzed according to the control protocol (CG-group): after a baseline walk of 20 m (NV-W1) patients received their routine BoNT/A injection and had to walk the same distance a second time (NV-W2). Approximately 3–5 weeks later, they had to walk a third time (NV-W3). A further seven patients (VG-group) were analyzed according to the vibration protocol: after a baseline walk (V-W1), patients underwent a first vibration training (VET1), walked a second time (V-W2), received their routine BoNT/A injection, and walked a third time (V-W3). About four weeks later, they had to walk again (V-W4), received another vibration training (VET3), and walked a fifth time (V-W5). At least six months after the analysis according to the vibration protocol, these patients were also analyzed according to the control protocol. Eleven gait parameters were compared between the CG- and VG-group, and within the VG-group. Result: Patients in the VG-group experienced a significant improvement in gait four weeks after BoNT/A injection, unlike the patients in the CG-group. VG-patients also showed improved gait after two VET sessions. However, there was no further functional improvement of gait when BoNT/A injections and VET sessions were combined. Conclusions: BoNT/A injections enhance functional mobility in patients with mild asymmetric leg spasticity. VET also induces an immediate gait improvement and offers a further treatment approach for leg spasticity. Whether combining BoNT treatment and vibration training offers superior outcomes compared to either treatment alone requires further investigation.
Multi-Stage Screening Purification: A New and Effective Method for Cleaning Diatom Samples from Marine Sediments
Authors: Deng Kong , Meng Mianmo , Lu Yangbo , Ji Wenming , Tang Guanxiong , Cai Guanqiang , Cui Qinyu , Lu Yongchao , Yang Feng , Zhang Dingjie , Liu Zhanhong
Published: January 2025

Diatoms are critical indicators in marine paleoecology and contemporary ecosystem studies, yet the accuracy of diatom analysis depends on effective purification methods. Current screening and purification techniques often yield low accuracy. This study introduces a multi-stage screening purification method that integrates both physical and chemical techniques to enhance the extraction of diatom remains from marine sediments, thereby improving the reliability of subsequent analysis. Using surface sediment samples from the Pacific Ocean, we compared the effectiveness of three purification methods: heavy liquid suspension purification, single-layer screening purification, and the newly developed multi-stage screening purification method. The study aimed to evaluate the impact of each method on diatom abundance, valve size distribution, and the accuracy of taxonomic identification. The results revealed that the multi-stage method significantly improved the accuracy of diatom abundance calculation. With this method, diatom abundance was 21.9 times higher than that obtained using the heavy liquid suspension method and 6.5 times higher than that obtained using the single-stage method. This method also proved to be cost-effective, easy to use, and produced samples with low impurity levels, which enhanced microscopic observation, identification, and the reliability of taxonomic statistics. Key factors influencing diatom abundance included sieve pore size, heavy liquid concentration, and valve size and density, while the type of acid and oxidant had minimal effect. Additionally, the multi-stage screening method facilitated the classification of diatoms into various size categories, providing a comprehensive view of diatom size distribution, including nano-sized diatoms (diameter < 20 μm) that are often overlooked in traditional studies. These findings demonstrate that the multi-stage screening purification method is an effective tool for improving the analysis of diatom remains in sediments, potentially refining the accuracy of diatom-based environmental investigations and paleoceanographic reconstructions.
Apis mellifera as a Model Species to Evaluate Toxicological Effects of Fungicides Used in Vineyard Agroecosystems
Authors: Campani Tommaso , Manieri Ginevra , Caliani Ilaria , Di Noi Agata , Casini Silvia
Published: January 2025

Agroecosystems provide habitats, food, and water for many pollinators and insects, but they are also heavily exposed to threats from the widespread use of pesticides and fertilizers. Managed honeybees and wild bees encounter pesticides in vineyards by collecting morning dew from vine leaves and accessing sugars from grapes, particularly during dry periods. This study assessed the toxicological effects of the commercial fungicide formulations Fantic FNCWG® and Ramedit combi®, both individually and in combination, on honeybees. Using a multi-biomarker approach, we evaluated neurotoxicity, metabolic disturbances, phase II detoxification processes, and immune system function. Our findings revealed that commercial fungicide mixtures with multiple active ingredients affect bees differently than single active compounds. Biomarker responses highlighted how these complex mixtures disrupt various enzymatic pathways; including immune function; altering critical enzyme kinetics involved in detoxification and potentially impairing essential bee functions. This study emphasizes the need for more comprehensive research into the sublethal effects of commercial pesticides, particularly those used in vineyards, which are understudied compared to pesticides used in orchards.
Beyond the Screen: How YouTube Influencers Shape Equity Investment Decisions
Authors: Pandey Lata Kumari , Singh Ranjit , Baker H. Kent , Laskar Habibur Rahman
Published: January 2025

This study examines how YouTube influencers can help shape equity decisions. We used a structured questionnaire with 26 questions to collect data using a purposive sample and the KMO and Bartlett tests to test the adequacy of the sample. Additionally, we used the Cronbach Alpha test to check the reliability of the questionnaire and principal component analysis to identify the factors related to YouTube influencers and their influence on equity investors. Our findings reveal a relationship between YouTube channel influencers and the financial decisions of equity investors. These factors influence credibility, influencer engagement, influencer trustworthiness, influencer investment fit, influencer’s YouTube channel promotion, and influencer-driven equity insights. This study could help investors make better decisions after learning pertinent information regarding equities. Investors can improve their investment strategies by identifying trustworthy and valuable influencer content by having a better understanding of these elements. This study provides novel insights into how digital content creators can shape equity investment decisions. However, a limitation of our study is that our findings do not show causality, only correlations between YouTube influencers and equity investments.