bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted Integration of siRNA against Porcine Cytomegalovirus (PCMV) Enhances the Resistance of Porcine Cells to PCMV
Authors: Mao Hongzhen , Li Jinyang , Gao Mengyu , Liu Xinmei , Zhang Haohan , Zhuang Yijia , He Tianyi , Zuo Wei , Bai Lang , Bao Ji
Published: April 2024

In the world’s first pig-to-human cardiac cytomegalovirus (PCMV), xenotransplant and elevated levels of porcine key factors contributing to patient mortality were considered. This has renewed attention on PCMV, a virus widely prevalent in pigs. Currently, there are no effective drugs or vaccines targeting PCMV, and its high detection difficulty poses challenges for prevention and control research. In this study, antiviral small hairpin RNA (shRNA) was selected and inserted into the Rosa26 and miR-17-92 loci of pigs via a CRISPR/Cas9-mediated knock-in strategy. Further in vitro viral challenge experiments demonstrated that these genetically edited pig cells could effectively limit PCMV replication. Through this process, we constructed a PCMV-infected cell model, validated partial viral interference sites, enhanced gene knock-in efficiency, performed gene editing at two different gene loci, and ultimately demonstrated that RNA interference (RNAi) technology combined with CRISPR/Cas9 has the potential to generate pig cells with enhanced antiviral infection capabilities. This opens up possibilities for the future production of pig populations with antiviral functionalities.
Cell-Free Culture Supernatant of Lactobacillus acidophilus AG01 and Bifidobacterium animalis subsp. lactis AG02 Reduces the Pathogenicity of NetB-Positive Clostridium perfringens in a Chicken Intestinal Epithelial Cell Line
Authors: Kadekar Darshana , Udrea Andreea Cornelia , Bak Steffen Yde , Christensen Niels , Gibbs Kirsty , Shen Chong , Bernardeau Marion
Published: April 2024

The worldwide reduction in the use of antibiotics in animal feed is fueling the need for alternatives for the prevention and control of poultry intestinal diseases such as necrotic enteritis (NE), which is caused by Clostridium perfringens. This is the first report on the use of an intestinal epithelial chicken cell line (CHIC-8E11) to study the pathogenic traits of C. perfringens and to investigate the mode of action of cell-free supernatants (CFS) from probiotic Lactobacillus acidophilus AG01 and Bifidobacterium animalis subsp. lactis AG02 in reducing the pathogenicity of C. perfringens. The cell adhesion, permeability and cytotoxicity were assessed under challenge with four C. perfringens strains isolated from broiler NE episodes of differing geographical origin (CP1–UK; CP10–Sweden; 25037–CP01 and CP22–USA). All the C. perfringens strains could adhere to the CHIC-8E11 cells, with varying affinity (0.05–0.48% adhesion across the strains). The CFS from one out of two strains (CP22) increased the cell permeability (+4.5-fold vs. the control, p < 0.01), as measured by the fluorescein isothiocyanate-dextran (FD4) content, with NetB toxin implicated in this effect. The CFS from all the strains was cytotoxic against the CHIC-8E11 cells in a dose- and strain-dependent manner (cytotoxicity 23–62% across the strains when dosed at 50 µL/mL, as assessed by the MTT cell viability assay). Pre-treatment of the cells with CFS from B. animalis subsp. lactis AG02 but not L. acidophilus AG01 reduced the cell adhesion of three out of four C. perfringens strains (by 77–85% vs. the control, p < 0.001) and reduced the negative effect of two NetB-positive strains on the cell permeability. The CFS of both probiotics alleviated the cytotoxicity of all the C. perfringens strains, which was dependent on the dose. The results confirm the suitability of the CHIC-8E11 cell line for the study of host–pathogen cell interactions in the context of NE caused by C. perfringens and reveal a beneficial mode of action of B. animalis subsp. lactis AG02 in reducing C. perfringens cell adhesion and, together with L. acidophilus AG01, in reducing C. perfringens cytotoxicity.
Investigation of Effects of Novel Bifidobacterium longum ssp. longum on Gastrointestinal Microbiota and Blood Serum Parameters in a Conventional Mouse Model
Authors: Rätsep Merle , Kilk Kalle , Zilmer Mihkel , Kuusik Sirje , Kuus Liina , Vallas Mirjam , Gerulis Oksana , Štšepetova Jelena , Orav Aivar , Songisepp Epp
Published: April 2024

Representatives of the genus Bifidobacterium are widely used as probiotics to modulate the gut microbiome and alleviate various health conditions. The action mechanisms of probiotics rely on their direct effect on the gut microbiota and the local and systemic effect of its metabolites. The main purpose of this animal experiment was to assess the biosafety of the Bifidobacterium longum strain BIOCC1719. Additional aims were to characterise the influence of the strain on the intestinal microbiota and the effect on several health parameters of the host during 15- and 30-day oral administration of the strain to mice. The strain altered the gut microbial community, thereby altering luminal short-chain fatty acid metabolism, resulting in a shift in the proportions of acetic, butyric, and propionic acids in the faeces and serum of the test group mice. Targeted metabolic profiling of serum revealed the possible ability of the strain to positively affect the hosts’ amino acids and bile acids metabolism, as the cholic acid, deoxycholic acid, aspartate, and glutamate concentration were significantly higher in the test group. The tendency to increase anti-inflammatory polyamines (spermidine, putrescine) and neuroprotective 3-indolepropionic acid metabolism and to lower uremic toxins (P-cresol-SO4, indoxyl-SO4) was registered. Thus, B. longum BIOCC1719 may exert health-promoting effects on the host through modulation of the gut microbiome and the host metabolome via inducing the production of health-promoting bioactive compounds. The health effects of the strain need to be confirmed in clinical trials with human volunteers.
Indirect Freeze Crystallization—An Emerging Technology for Valuable Resource Recovery from Wastewater
Authors: More Kagiso , Maree Johannes , Mahlangu Mlungisi
Published: April 2024

This paper explores the efficiency and potential of indirect freeze crystallization (IFC) as a valuable resource-recovery technology in wastewater treatment, particularly focusing on acid mine water and hazardous material wastewater-treatment plants. Wastewater treatment poses challenges to recovering valuable resources effectively, enforcing the need for sustainable and resource-efficient technologies like freeze crystallization. Through a thorough examination of IFC principles and mechanisms, this paper aims to highlight its applications, advantages, and limitations. The investigation includes a comprehensive literature review and detailed methodology from one of the IFC pilot plants, as well as a critical analysis of the environmental and economic implications of IFC. By addressing scaling challenges in reverse osmosis and proposing an environmentally friendly brine disposal method through IFC, this paper contributes to reducing the environmental footprint associated with wastewater treatment. Additionally, this paper highlights the importance of extracting valuable resources from highly saline water and emphasises the potential economic and environmental benefits of resource recovery, particularly focusing on the promising technology of IFC.
An Automated Approach to the Heterogeneity Test for Sampling Protocol Optimization
Authors: Prado Gabriela Cardoso , Chieregati Ana Carolina , Dominy Simon C.
Published: April 2024

The fundamental sampling error is one of the sampling errors defined by Pierre Gy’s Theory of Sampling and is related to the constitution heterogeneity of the mineralisation. Even if a sampling procedure is considered ideal or perfect, this error will still exist and, therefore, cannot be eliminated. A key input into Gy’s fundamental sampling error equation is intrinsic heterogeneity. The intrinsic heterogeneity of a fragmented lot can be estimated by the “calibrated” formula of Gy, which can be written as a function of the sampling constants K and α. These constants can be calibrated by the standard heterogeneity test, originally developed by Pierre Gy and Francis Pitard. This method is based on the selection of rock fragments, individually and randomly, in an equiprobabilistic way from a lot of particulate material, aiming to estimate the intrinsic heterogeneity of the lot. This test, in addition to demanding time and space, can be influenced by human biases, and is difficult to quantify or measure. Aiming to simplify the test execution and eliminate the variance generated by human biases, a prototype called the intrinsic heterogeneity tester was developed as an automated alternative for heterogeneity testing. This prototype selects fragments from a falling stream, one by one, by means of a predefined laser count. To evaluate the prototype, a study was carried out, using painted chickpeas to simulate mineralisation grades and, sequentially, processing the same lot in the intrinsic heterogeneity tester prototype several times. The statistical and mineral content analysis, and comparisons between the intrinsic heterogeneity tester and the standard heterogeneity test sampling constants and constitution heterogeneities were undertaken. As a result, the authors conclude that the intrinsic heterogeneity tester prototype can be used as an alternative to the manual selection of individual fragments and for estimating the intrinsic heterogeneity of particulate material lots to support sampling protocol optimization.
Analysis Transcriptome and Phytohormone Changes Associated with the Allelopathic Effects of Ginseng Hairy Roots Induced by Different-Polarity Ginsenoside Components
Authors: Zhou Tingting , Li Qiong , Huang Xin , Chen Changbao
Published: April 2024

The allelopathic autotoxicity of ginsenosides is an important cause of continuous cropping obstacles in ginseng planting. There is no report on the potential molecular mechanism of the correlation between polarity of ginsenoside components and their allelopathic autotoxicity. This study applied a combination of metabolomics and transcriptomics analysis techniques, combined with apparent morphology, physiological indexes, and cell vitality detection of the ginseng hairy roots, through which the molecular mechanism of correlation between polarity and allelopathic autotoxicity of ginsenosides were comprehensively studied. The hairy roots of ginseng presented more severe cell apoptosis under the stress of low-polarity ginsenoside components (ZG70). ZG70 exerted allelopathic autotoxicity by regulating the key enzyme genes of cis-zeatin (cZ) synthesis pathway, indole-3-acetic acid (IAA) synthesis pathway, and jasmonates (JAs) signaling transduction pathway. The common pathway for high-polarity ginsenoside components (ZG50) and ZG70 to induce the development of allelopathic autotoxicity was through the expression of key enzymes in the gibberellin (GA) signal transduction pathway, thereby inhibiting the growth of ginseng hairy roots. cZ, indole-3-acetamid (IAM), gibberellin A1 (GA1), and jasmonoyl-L-isoleucine (JA-ILE) were the key response factors in this process. It could be concluded that the polarity of ginsenoside components were negatively correlated with their allelopathic autotoxicity.
Design of Na3MnZr(PO4)3/Carbon Nanofiber Free-Standing Cathodes for Sodium-Ion Batteries with Enhanced Electrochemical Performances through Different Electrospinning Approaches
Authors: Conti Debora Maria , Urru Claudia , Bruni Giovanna , Galinetto Pietro , Albini Benedetta , Milanese Chiara , Pisani Silvia , Berbenni Vittorio , Capsoni Doretta
Published: April 2024

The NASICON-structured Na3MnZr(PO4)3 compound is a promising high-voltage cathode material for sodium-ion batteries (SIBs). In this study, an easy and scalable electrospinning approach was used to synthesize self-standing cathodes based on Na3MnZr(PO4)3 loaded into carbon nanofibers (CNFs). Different strategies were applied to load the active material. All the employed characterization techniques (X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), thermal gravimetric analysis (TGA), and Raman spectroscopy) confirmed the successful loading. Compared to an appositely prepared tape-cast electrode, Na3MnZr(PO4)3/CNF self-standing cathodes demonstrated an enhanced specific capacity, especially at high C-rates, thanks to the porous conducive carbon nanofiber matrix. Among the strategies applied to load Na3MnZr(PO4)3 into the CNFs, the electrospinning (vertical setting) of the polymeric solution containing pre-synthesized Na3MnZr(PO4)3 powders resulted effective in obtaining the quantitative loading of the active material and a homogeneous distribution through the sheet thickness. Notably, Na3MnZr(PO4)3 aggregates connected to the CNFs, covered their surface, and were also embedded, as demonstrated by TEM and EDS. Compared to the self-standing cathodes prepared with the horizontal setting or dip–drop coating methods, the vertical binder-free electrode exhibited the highest capacity values of 78.2, 55.7, 38.8, 22.2, 16.2, 12.8, 10.3, 9.0, and 8.5 mAh/g at C-rates of 0.05C, 0.1C, 0.2C, 0.5C, 1C, 2C, 5C, 10C, and 20C, respectively, with complete capacity retention at the end of the measurements. It also exhibited a good cycling life, compared to its tape-cast counterpart: it displayed higher capacity retention at 0.2C and 1C, and, after cycling 1000 cycles at 1C, it could be further cycled at 5C, 10C, and 20C.
Effects of Red Sorghum-Derived Deoxyanthocyanidins and Their O-β-D-Glucosides on E-Cadherin Promoter Activity in PC-3 Prostate Cancer Cells
Authors: Mora Nathalie , Rosa Maxence , Touaibia Mohamed , Martin Luc J.
Published: April 2024

Although much less common than anthocyanins, 3-Deoxyanthocyanidins (3-DAs) and their glucosides can be found in cereals such as red sorghum. It is speculated that their bioavailability is higher than that of anthocyanins. Thus far, little is known regarding the therapeutic effects of 3-DAs and their O-β-D-glucosides on cancer, including prostate cancer. Thus, we evaluated their potential to decrease cell viability, to modulate the activity of transcription factors such as NFκB, CREB, and SOX, and to regulate the expression of the gene CDH1, encoding E-Cadherin. We found that 4′,7-dihydroxyflavylium chloride (P7) and the natural apigeninidin can reduce cell viability, whereas 4′,7-dihydroxyflavylium chloride (P7) and 4′-hydroxy-7-O-β-D-glucopyranosyloxyflavylium chloride (P3) increase the activities of NFkB, CREB, and SOX transcription factors, leading to the upregulation of CDH1 promoter activity in PC-3 prostate cancer cells. Thus, these compounds may contribute to the inhibition of the epithelial-to-mesenchymal transition in cancer cells and prevent the metastatic activity of more aggressive forms of androgen-resistant prostate cancer.
Phosphorus Modification of Iron: Mechanistic Insights into Ammonia Synthesis on Fe2P Catalyst
Authors: Almithn Abdulrahman
Published: April 2024

Ammonia (NH3) is a critical chemical for fertilizer production and a potential future energy carrier within a sustainable hydrogen economy. The industrial Haber–Bosch process, though effective, operates under harsh conditions due to the high thermodynamic stability of the nitrogen molecule (N2). This motivates the search for alternative catalysts that facilitate ammonia synthesis at milder temperatures and pressures. Theoretical and experimental studies suggest that circumventing the trade-off between N–N activation and subsequent NHx hydrogenation, governed by the Brønsted–Evans–Polanyi (BEP) relationship, is key to achieving this goal. Recent studies indicate metal phosphides as promising catalyst materials. In this work, a comprehensive density functional theory (DFT) study comparing the mechanisms and potential reaction pathways for ammonia synthesis on Fe(110) and Fe2P(001) is presented. The results reveal substantial differences in the adsorption strengths of NHx intermediates, with Fe2P(001) exhibiting weaker binding compared to Fe(110). For N–N bond cleavage, multiple competing pathways become viable on Fe2P(001), including routes involving the pre-hydrogenation of adsorbed N2 (e.g., through *NNH*). Analysis of DFT-derived turnover rates as a function of hydrogen pressure (H2) highlights the increased importance of these hydrogenated intermediates on Fe2P(001) compared to Fe(110) where direct N2 dissociation dominates. These findings suggest that phosphorus incorporation modifies the ammonia synthesis mechanism, offering alternative pathways that may circumvent the limitations of traditional transition metal catalysts. This work provides theoretical insights for the rational design of Fe-based catalysts and motivates further exploration of phosphide-based materials for sustainable ammonia production.
Predictive and Prognostic Biomarkers and Tumor Antigens for Targeted Therapy in Urothelial Carcinoma
Authors: Eturi Aditya , Bhasin Amman , Zarrabi Kevin K. , Tester William J.
Published: April 2024

Urothelial carcinoma (UC) is the fourth most prevalent cancer amongst males worldwide. While patients with non-muscle-invasive disease have a favorable prognosis, 25% of UC patients present with locally advanced disease which is associated with a 10–15% 5-year survival rate and poor overall prognosis. Muscle-invasive bladder cancer (MIBC) is associated with about 50% 5 year survival when treated by radical cystectomy or trimodality therapy; stage IV disease is associated with 10–15% 5 year survival. Current therapeutic modalities for MIBC include neoadjuvant chemotherapy, surgery and/or chemoradiation, although patients with relapsed or refractory disease have a poor prognosis. However, the rapid success of immuno-oncology in various hematologic and solid malignancies offers new targets with tremendous therapeutic potential in UC. Historically, there were no predictive biomarkers to guide the clinical management and treatment of UC, and biomarker development was an unmet need. However, recent and ongoing clinical trials have identified several promising tumor biomarkers that have the potential to serve as predictive or prognostic tools in UC. This review provides a comprehensive summary of emerging biomarkers and molecular tumor targets including programmed death ligand 1 (PD-L1), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor (FGFR), DNA damage response and repair (DDR) mutations, poly (ADP-ribose) polymerase (PARP) expression and circulating tumor DNA (ctDNA), as well as their clinical utility in UC. We also evaluate recent advancements in precision oncology in UC, while illustrating limiting factors and challenges related to the clinical application of these biomarkers in clinical practice.
Anti-Tumor Activity and Mechanism of Silibinin Based on Network Pharmacology and Experimental Verification
Authors: Li Peihai , Wang Dexu , Yang Xueliang , Liu Changyu , Li Xiaobin , Zhang Xuanming , Liu Kechun , Zhang Yun , Zhang Mengqi , Wang Changyun , Wang Rongchun
Published: April 2024

Silibinin is a flavonoid compound extracted from the seeds of Silybum marianum (L.) Gaertn. It has the functions of liver protection, blood-lipid reduction and anti-tumor effects. However, the potential molecular mechanism of silibinin against tumors is still unknown. This study aimed to assess the anti-tumor effects of silibinin in adenoid cystic carcinoma (ACC2) cells and Balb/c nude mice, and explore its potential mechanism based on network pharmacology prediction and experimental verification. A total of 347 targets interacting with silibinin were collected, and 75 targets related to the tumor growth process for silibinin were filtrated. Based on the PPI analysis, CASP3, SRC, ESR1, JAK2, PRKACA, HSPA8 and CAT showed stronger interactions with other factors and may be the key targets of silibinin for treating tumors. The predicted target proteins according to network pharmacology were verified using Western blot analysis in ACC2 cells and Balb/c nude mice. In the pharmacological experiment, silibinin was revealed to significantly inhibit viability, proliferation, migration and induce the apoptosis of ACC2 cells in vitro, as well as inhibit the growth and development of tumor tissue in vivo. Western blot analysis showed that silibinin affected the expression of proteins associated with cell proliferation, migration and apoptosis, such as MMP3, JNK, PPARα and JAK. The possible molecular mechanism involved in cancer pathways, PI3K-Akt signaling pathway and viral carcinogenesis pathway via the inhibition of CASP3, MMP3, SRC, MAPK10 and CDK6 and the activation of PPARα and JAK. Overall, our results provided insight into the pharmacological mechanisms of silibinin in the treatment of tumors. These results offer a support for the anti-tumor uses of silibinin.
Size-Dependent High-Pressure Behavior of Pure and Eu3+-Doped Y2O3 Nanoparticles: Insights from Experimental and Theoretical Investigations
Authors: Pereira André Luis de Jesus , Sans Juan Ángel , Gomis Óscar , Santamaría-Pérez David , Ray Sudeshna , Godoy Armstrong , da Silva-Sobrinho Argemiro Soares , Rodríguez-Hernández Plácida , Muñoz Alfonso , Popescu Catalin , Manjón Francisco Javier
Published: April 2024

We report a joint high-pressure experimental and theoretical study of the structural, vibrational, and photoluminescent properties of pure and Eu3+-doped cubic Y2O3 nanoparticles with two very different average particle sizes. We compare the results of synchrotron X-ray diffraction, Raman scattering, and photoluminescence measurements in nanoparticles with ab initio density-functional simulations in bulk material with the aim to understand the influence of the average particle size on the properties of pure and doped Y2O3 nanoparticles under compression. We observe that the high-pressure phase behavior of Y2O3 nanoparticles depends on the average particle size, but in a different way to that previously reported. Nanoparticles with an average particle size of ~37 nm show the same pressure-induced phase transition sequence on upstroke and downstroke as the bulk sample; however, nanoparticles with an average particle size of ~6 nm undergo an irreversible pressure-induced amorphization above 16 GPa that is completed above 24 GPa. On downstroke, 6 nm nanoparticles likely consist of an amorphous phase.
Structural and Morphological Studies of Pt in the As-Grown and Encapsulated States and Dependency on Film Thickness
Authors: Nergis Berkin , Bauer Sondes , Jin Xiaowei , Horak Lukas , Schneider Reinhard , Holy Vaclav , Seemann Klaus , Ulrich Sven , Baumbach Tilo
Published: April 2024

The morphology and crystal structure of Pt films grown by pulsed laser deposition (PLD) on yttria-stabilized zirconia (YSZ)at high temperatures Tg = 900 °C was studied for four different film thicknesses varying between 10 and 70 nm. During the subsequent growth of the capping layer, the thermal stability of the Pt was strongly influenced by the Pt film’s thickness. Furthermore, these later affected the film morphology, the crystal structure and hillocks size, and distribution during subsequent growth at Tg = 900 °C for a long duration. The modifications in the morphology as well as in the structure of the Pt film without a capping layer, named also as the as-grown and encapsulated layers in the bilayer system, were examined by a combination of microscopic and scattering methods. The increase in the thickness of the deposited Pt film brought three competitive phenomena into occurrence, such as 3D–2D morphological transition, dewetting, and hillock formation. The degree of coverage, film continuity, and the crystal quality of the Pt film were significantly improved by increasing the deposition time. An optimum Pt film thickness of 70 nm was found to be suitable for obtaining a hillock-free Pt bottom electrode which also withstood the dewetting phenomena revealed during the subsequent growth of capping layers. This achievement is crucial for the deposition of functional bottom electrodes in ferroelectric and multiferroic heterostructure systems.
Effect of Enriched Environment on Cerebellum and Social Behavior of Valproic Zebrafish
Authors: Flores-Prieto Bernardo , Caycho-Salazar Flower , Manzo Jorge , Hernández-Aguilar María Elena , Coria-Avila Alfonso Genaro , Herrera-Covarrubias Deissy , Rojas-Dúran Fausto , Aranda-Abreu Gonzalo Emiliano , Pérez-Estudillo Cesar Antonio , Toledo-Cárdenas María Rebeca
Published: April 2024

The etiology of autism spectrum disorder (ASD) has been linked to both genetic and epigenetic factors. Among the epigenetic factors, exposure to valproic acid (VPA), an antiepileptic and mood-modulating drug, has been shown to induce characteristic traits of ASD when exposed to during embryogenesis. Conversely, in animal models, enriched environment (EE) has demonstrated positive behavioral and neural effects, suggesting its potential as a complementary treatment to pharmacological approaches in central nervous system disorders. In this study, we utilized zebrafish to model ASD characteristics induced by VPA and hypothesized that sensory stimulation through EE could ameliorate the behavioral and neuroanatomical features associated with ASD. To test this hypothesis, we assessed social behavior, cerebellar volume, and Purkinje cell populations via histology and immunohistochemistry after exposing the fish to EE. The results revealed that zebrafish exposed to VPA exhibited social deficits, reduced cerebellar cortex volume, and a decrease in c-Fos-positive cells in the Purkinje layer. In contrast, VPA-exposed fish treated with EE showed increased socialization, augmented cerebellar cortex volume, and an elevation in c-Fos-positive Purkinje cells. These findings suggest that alterations induced by VPA may be ameliorated through EE treatment, highlighting the potential therapeutic impact of sensory stimulation in conditions related to ASD.
Weight Loss Trajectories and Short-Term Prediction in an Online Weight Management Program
Authors: Zhou Bingjie , Roberts Susan B. , Das Sai Krupa , Naumova Elena N.
Published: April 2024

The extent to which early weight loss in behavioral weight control interventions predicts long-term success remains unclear. In this study, we developed an algorithm aimed at classifying weight change trajectories and examined its ability to predict long-term weight loss based on weight early change. We utilized data from 667 de-identified individuals who participated in a commercial weight loss program (Instinct Health Science), comprising 69,363 weight records. Sequential polynomial regression models were employed to classify participants into distinct weight trajectory patterns based on key model parameters. Next, we applied multinomial logistic models to evaluate if early weight loss in the first 14 days and prolonged duration of participation were significantly associated with long-term weight loss patterns. The mean percentage of weight loss was 7.9 ± 5.1% over 133 ± 69 days. Our analysis revealed four main weight loss trajectory patterns: a steady decrease over time (30.6%), a decrease to a plateau with subsequent decline (15.8%), a decrease to a plateau with subsequent increase (46.9%), and no substantial decrease (6.7%). Early weight change rate and total participating duration emerged as significant factors in differentiating long-term weight loss patterns. These findings contribute to support the provision of tailored advice in the early phase of behavioral interventions for weight loss.
Effects of Gluten on Gut Microbiota in Patients with Gastrointestinal Disorders, Migraine, and Dermatitis
Authors: San Mauro Martín Ismael , López Oliva Sara , Garicano Vilar Elena , Sánchez Niño Guerthy Melissa , Penadés Bruno F. , Terrén Lora Ana , Sanz Rojo Sara , Collado Yurrita Luis
Published: April 2024

As gluten may trigger gastrointestinal disorders (GIDs), its presence or absence in the diet can change the diversity and proportion of gut microbiota. The effects of gluten after six weeks of a double-blind, placebo-controlled intervention with a gluten-free diet (GFD) were studied in participants with GIDs suffering from migraines and atopic dermatitis (n = 46). Clinical biomarkers, digestive symptoms, stool, the Migraine Disability Assessment questionnaire, and zonulin levels were analyzed. Next-generation sequencing was used to amplify the 16S rRNA gene of bacteria and the internal transcribed spacer (ITS) regions of fungi. The GFD increased Chao1 fungal diversity after the intervention, while the fungal composition showed no changes. Bacterial diversity and composition remained stable, but a positive association between bacterial and fungal Chao1 diversity and a negative association between Dothideomycetes and Akkermansia were observed. GIDs decreased in both groups and migraines improved in the placebo group. Our findings may aid the development of GID treatment strategies.
Effects of Wheat Biscuits Enriched with Plant Proteins Incorporated into an Energy-Restricted Dietary Plan on Postprandial Metabolic Responses of Women with Overweight/Obesity
Authors: Kanata Maria-Christina , Yanni Amalia E. , Koliaki Chrysi , Pateras Irene , Anastasiou Ioanna A. , Kokkinos Alexander , Karathanos Vaios T.
Published: April 2024

This study investigates the effect of daily consumption of wheat biscuits enriched with plant proteins in postprandial metabolic responses of women with overweight/obesity who follow an energy-restricted diet. Thirty apparently healthy women participated in a 12-week randomized controlled trial and were assigned either to a control (CB) or an intervention (PB) group. Participants consumed daily either a conventional (CB) or an isocaloric wheat biscuit enriched with plant proteins (PB) containing high amounts of amino acids with appetite-regulating properties, i.e., BCAAs and L-arg. At baseline and the end of the intervention, a mixed meal tolerance test was performed. The responses of glucose, insulin, ghrelin, GLP-1, and glicentin were evaluated over 180 min. After 12 weeks, both groups experienced significant decreases in body weight, fat mass, and waist circumference. In the PB group, a trend towards higher weight loss was observed, accompanied by lower carbohydrate, fat, and energy intakes (p < 0.05 compared to baseline and CB group), while decreases in fasting insulin and the HOMA-IR index were also observed (p < 0.05 compared to baseline). In both groups, similar postprandial glucose, ghrelin, and GLP-1 responses were detected, while iAUC for insulin was lower (p < 0.05). Interestingly, the iAUC of glicentin was greater in the PB group (p < 0.05 compared to baseline). Subjective appetite ratings were beneficially affected in both groups (p < 0.05). Consumption of wheat biscuits enriched in plant proteins contributed to greater weight loss, lower energy intake, and insulin resistance and had a positive impact on postprandial glicentin response, a peptide that can potentially predict long-term weight loss and decreased food intake.
Association between Oral Health and Depressive Symptoms in Chinese Older Adults: The Mediating Role of Dietary Diversity
Authors: Lou Jiaxu , Wang Jian , Fu Yingjie , Huang Derong , Liu Mei , Zhao Ruonan , Deng Jiahui
Published: April 2024

Diet is a modifiable factor in healthy population aging. Additionally, oral health and diet are important factors affecting depressive symptoms. To assess the mediating role of dietary diversity (DD) in oral health and depressive symptoms in older adults, we selected 8442 participants aged ≥ 65 years from the 2018 Chinese Longitudinal Health Longevity Survey (CLHLS) for a cross-sectional study. Depressive symptoms were determined based on scores on the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10). Dietary diversity scores (DDS) were established based on the frequency of intake of food groups. Oral health was measured by denture use and toothbrushing frequency. Stepwise multiple linear regression and PROCESS macros were used for mediated effects analysis and testing. The sample had a positive detection rate of 44.1% for depressive symptoms, 40.8% for denture use, and 41.9% for once-a-day toothbrushing. Denture use (ρ = −0.077, p < 0.01) and toothbrushing frequency (ρ = −0.115, p < 0.01) were negative predictors of depressive symptoms in older adults. DD significantly mediated the association between denture use (indirect effect −0.047; 95%CI: −0.068–0.028; p < 0.001), toothbrushing frequency (indirect effect −0.041; 95%CI: −0.054–0.030; p < 0.001), and depressive symptoms. Denture use and toothbrushing frequency not only directly reduce the risk of depressive symptoms in older adults, but also indirectly affect depressive symptoms through DD.
Antimicrobial Activity of Methylene Blue Associated with Photodynamic Therapy: In Vitro Study in Multi-Species Oral Biofilm
Authors: Bueno-Silva Bruno , Parma-Garcia Javier , Frigo Lucio , Suárez Lina J. , Macedo Tatiane Tiemi , Uyeda Fábio Hideaki , Melo Marcelo Augusto Ruiz da Cunha , Sacco Roberto , Mourão Carlos Fernando , Feres Magda , Shibli Jamil Awad , Figueiredo Luciene Cristina
Published: April 2024

The control of infectious diseases caused by biofilms is a continuing challenge for researchers due to the complexity of their microbial structures and therapeutic implications. Photodynamic therapy as an adjunctive anti-infective treatment has been described as a possible valid approach but has not been tested in polymicrobial biofilm models. This study evaluated the effect of photodynamic therapy in vitro with methylene blue (MB) 0.01% and red LEDs (λ = 660 nm, power density ≈ 330 mW/cm2, 2 mm distance from culture) on the metabolic activity and composition of a multispecies subgingival biofilm. Test Groups LED and MB + LED showed a more significant reduction in metabolic activity than the non-LED application group (~50 and 55%, respectively). Groups LED and MB equally affected (more than 80%) the total bacterial count in biofilms. No differences were noted in the bacterial biofilm composition between the groups. In vitro LED alone or the MB + LED combination reduced the metabolic activity of bacteria in polymicrobial biofilms and the total subgingival biofilm count.
Spatial Distribution of Dermanyssus gallinae Infestations in Greece and Their Association with Ambient Temperature, Humidity, and Altitude
Authors: Sioutas Georgios , Gelasakis Athanasios I. , Papadopoulos Elias
Published: April 2024

Dermanyssus gallinae, the poultry red mite (PRM), is the most prevalent and harmful ectoparasite of laying hens globally. Although prevalence and risk factor studies can help veterinarians make decisions regarding farm treatments, relevant data are scarce. The present study investigated the prevalence and infestation severity of PRM in poultry farms across Greece and examined potential risk factors. AviVet traps were used to sample 84 farms (51 backyard, 33 industrial) over three years. Farm altitude, temperature, humidity, region, and production systems were assessed as potential risk factors with chi-square tests, initially for all the studied farms and then exclusively for backyard farms. The overall prevalence was 75.0% and was higher in backyard farms (80.4%) compared with industrial ones (66.7%), varying regionally from 66.7 to 90.9%. Altitude and temperature were not significant risk factors, but farms with humidity <60% had a lower infestation risk. Infestation severity did not significantly differ by risk factors. The poultry red mite is highly prevalent across Greek poultry production systems and regions. In the future, global warming, reduced acaricide options, and a ban on cage systems will all threaten a wider spatio-temporal distribution of the PRM, justifying the urgent need for effective monitoring and control methods to protect hen production and welfare and workers’ health.
Seroprevalence and Risk Factors Associated with Phleboviruses and Crimean–Congo Hemorrhagic Fever Virus among Blood Donors in Central Tunisia
Authors: Ayari Rym , Chaouch Houda , Findlay-Wilson Stephen , Hachfi Wissem , Ben Lasfar Nadia , Bellazreg Foued , Dowall Stuart , Hannachi Neila , Letaief Amel
Published: April 2024

The aim of this study was to determine the prevalence of six viruses, from two families of the order Bunyavirales, in the general population of central Tunisia. Sera collected from 377 asymptomatic blood donors were serologically assayed for Rift Valley fever virus (RVFV), Crimean–Congo hemorrhagic fever virus (CCHFV), and four sandfly-borne phleboviruses: Toscana virus (TOSV), sandfly fever Naples virus (SFNV), sandfly fever Sicilian virus (SFSV), and sandfly fever Cyprus virus (SFCV). Of the 377 subjects enrolled in this study, 17.3% were IgG positive for at least one of the viruses tested. The most frequently detected antibodies were against TOSV (13.3%), followed by SFCV (2.9%), RVFV (1.9%), SFSV (1.3%), and SFNV (1.1%). Only one sample was IgG positive for CCHFV. Dual reactivity was observed in nine cases: SFSV + SFCV in three cases (0.8%) and TOSV + SFNV, TOSV + SFCV, and TOSV + RVFV in two cases (0.5%) each. 15.9% of donors were IgG positive against sandfly-borne phleboviruses. Among the 65 donors IgG positive for phleboviruses, 50.8% were from rural areas compared to 12.3% from urban areas (p < 0.001); 92.3% had animals in their living quarters (p = 0.009); and 70.8% lived in the vicinity of stagnant water (p = 0.062). Seroprevalence was significantly higher among donors living with chronic diseases (p = 0.039). Furthermore, the seroprevalence of phleboviruses was higher in Kairouan, the central governorate, than in the two coastal governorates: Monastir and Sousse, with 33.4%, 24.2%, and 14.9%, respectively. The presence of antibodies in the general population needs further investigation to better assess the extent of these viruses. Only TOSV was known to have an extensive circulation in Tunisia and in North Africa. Continued surveillance and interventions are necessary to detect the emergence of all arboviruses and to prevent further transmission.
The Role of α-Enolase on the Production of Interleukin (IL)-32 in Con A-Mediated Inflammation and Rheumatoid Arthritis (RA)
Authors: Jo Hyejung , Shin Seulgi , Agura Tomoyo , Jeong Seoyoun , Ahn Hyovin , Lee Junmyung , Kim Yejin , Kang Jae Seung
Published: April 2024

Interleukin (IL)-32 is produced by T lymphocytes, natural killer cells, monocytes, and epithelial cells. IL-32 induces the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, IL-1β, IL-6, and IL-8, and IL-32 expression is highly increased in rheumatoid arthritis (RA) patients. Enolase-1 (ENO1) is a glycolytic enzyme and the stimulation of ENO1 induces high levels of pro-inflammatory cytokines in concanavalin A (Con A)-activated peripheral blood mononuclear cells (PBMCs) and macrophages in RA patients. In addition, there are many reports that anti-ENO1 antibody is correlated with the disease progression of RA. It implies that ENO1 could regulate IL-32 production during inflammation related to the pathogenesis of RA. Therefore, we investigated the role of ENO1 in IL-32 production using Con A-activated PBMCs and RA PBMCs. IL-32 expression is increased by ENO1 stimulation using real-time PCR and ELISA. In addition, we confirmed that IL-32 production was decreased in Con A-activated PBMCs and RA PBMCs pre-treated with NF-κB or p38 MAPK pathway inhibitors. Taken together, these results suggest that ENO1 plays an important role in inflammation through the induction of IL-32 production by the activation of the NF-κB and p38 MAPK pathways.
Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective
Authors: Danielpour David
Published: April 2024

The TGF-β family is a group of 25 kDa secretory cytokines, in mammals consisting of three dimeric isoforms (TGF-βs 1, 2, and 3), each encoded on a separate gene with unique regulatory elements. Each isoform plays unique, diverse, and pivotal roles in cell growth, survival, immune response, and differentiation. However, many researchers in the TGF-β field often mistakenly assume a uniform functionality among all three isoforms. Although TGF-βs are essential for normal development and many cellular and physiological processes, their dysregulated expression contributes significantly to various diseases. Notably, they drive conditions like fibrosis and tumor metastasis/progression. To counter these pathologies, extensive efforts have been directed towards targeting TGF-βs, resulting in the development of a range of TGF-β inhibitors. Despite some clinical success, these agents have yet to reach their full potential in the treatment of cancers. A significant challenge rests in effectively targeting TGF-βs’ pathological functions while preserving their physiological roles. Many existing approaches collectively target all three isoforms, failing to target just the specific deregulated ones. Additionally, most strategies tackle the entire TGF-β signaling pathway instead of focusing on disease-specific components or preferentially targeting tumors. This review gives a unique historical overview of the TGF-β field often missed in other reviews and provides a current landscape of TGF-β research, emphasizing isoform-specific functions and disease implications. The review then delves into ongoing therapeutic strategies in cancer, stressing the need for more tools that target specific isoforms and disease-related pathway components, advocating mechanism-based and refined approaches to enhance the effectiveness of TGF-β-targeted cancer therapies.
An Effective Method to Prepare Curcumin-Loaded Soy Protein Isolate Nanoparticles Co-Stabilized by Carrageenan and Fucoidan
Authors: Chen Yaxin , Cai Shuyun , He Niaoniao , Huang Xiaomei , Hong Zhuan , He Jianlin , Chen Hui , Zhang Yiping
Published: April 2024

In this study, a novel and simple strategy is proposed based on 3D network formed by easily blending polysaccharide carrageenan (Car) and fucoidan (Fuc) without a crosslinker. The Fuc/Car dual coating effectively assists the self-assembly of soy protein-isolated (SPI)/curcumin (Cur, C) composite microcapsules (SPI/C) and achieves an excellent curcumin encapsulation efficiency (EE) up to 95.28% with a 4.16% loading capacity (LC) under optimal conditions. The resulting nanocomposites achieved a satisfying redispersibility in aqueous solution and enhanced the water solubility with a lower size dispersity index (PDI) of 0.12 and a larger zeta potential of −29.67 mV. The Fuc/Car double-layer network not only dramatically improved its thermal stability and photostability, but also provided controlled release and enhanced antioxidant activity in in vitro conditions. The underlying mechanism of the self-assembly of the curcumin-loaded nanoparticles was also addressed. The results proved the feasibility of the encapsulation of unstable hydrophobic bioactive substances (curcumin) with the dual anionic polysaccharide Fuc/Car co-stabilized SPI nanoparticles. This study paves the way for an alternative way of developing novel curcumin delivery systems and will have broad prospects in the pharmaceutical industries.
Modulating the Nature of Ionizable Lipids and Number of Layers in Hyaluronan-Decorated Lipid Nanoparticles for In Vitro Delivery of RNAi
Authors: Passos Gibson Victor , Tahiri Houda , Gilbert Claudia , Yang Chun , Phan Quoc Thang , Banquy Xavier , Hardy Pierre
Published: April 2024

Lipid nanoparticles (LNPs) have established their position as nonviral vectors for gene therapy. Tremendous efforts have been made to modulate the properties of LNPs to unleash their full clinical potential. Among the strategies being pursued, the layer-by-layer (LbL) technique has gained considerable attention in the biomedical field. Illuminated by our previous work, here we investigate if the LbL approach could be used to modify the LNP cores formulated with three different ionizable lipids: DODMA, MC3, and DODAP. Additionally, we wondered if more than three layers could be loaded onto LNPs without disrupting their gene transfection ability. Taking advantage of physicochemical analysis, as well as uptake and gene silencing studies, we demonstrate the feasibility of modifying the surface of LNPs with the LbL assembly. Precisely, we successfully modified three different LNPs using the layer-by-layer strategy which abrogated luciferase activity in vitro. Additionally, we constructed a 5×-layered HA-LNP containing the MC3 ionizable lipid which outperformed the 3×-layered counterpart in transfecting miRNA-181-5p to the pediatric GBM cell line, as a proof-of-concept in vitro experiment. The method used herein has been proven reproducible, of easy modification to adapt to different ionizable lipid-containing LNPs, and holds great potential for the translation of RNA-based therapeutic strategies.
Development of a Micropropagation Protocol for the Ex Situ Conservation of Nuttall’s Scrub Oak (Quercus dumosa)
Authors: Ree Joseph Francis , Powell Christy , Folgado Raquel , Pence Valerie C. , Walters Christina , Maschinski Joyce
Published: April 2024

Worldwide, oak species are threatened with extinction due to habitat loss, pathogens, and changing fire regimes. Ex situ conservation through tissue culture may protect the remaining genetic diversity of Quercus dumosa, or the coastal sage scrub oak, from further loss. We designed three basal salt formulations based on the mineral composition of shoot tips and first leaves from mature Q. dumosa and explored carbohydrate source, stress-mitigating compounds, and plant growth regulator concentrations to develop a method of cultivating many Q. dumosa culture lines in vitro. All three novel basal salt formulations led to decreased necrosis compared with commercial basal salt formulas WPM, MS, and DKW. Substitution of 30 g L−1 sucrose with glucose and adding 250 mg L−1 ascorbic acid, 5.2 mg L−1 SNP sodium nitroprusside, and 103 mg L−1 y-aminobutyric acid improved culture health overall. In an experiment involving 115 culture lines, 0.66 mg L−1 6-benzylaminopurine produced the highest average shoots per explant, but 0.33 mg L−1 produced the greatest proportion of shoots 2 cm or greater. Incubation for 24 h in 20 mg L−1 indole-3-butyric acid led to the most rooting. These methods show promise for the ex situ conservation of many genotypes of endangered Q. dumosa.
Development of a TaqMan Real-Time PCR for Early and Accurate Detection of Anthracnose Pathogen Colletotrichum siamense in Pachira glabra
Authors: Gu Jiaqi , Wang Haihua , Huang Xiaoyan , Liao Limei , Xie Huan , Peng Xixu
Published: April 2024

Anthracnose, caused by Colletotrichum siamense, is a destructive disease of Pachira glabra in southern China. Early and proper monitoring and quantification of C. siamense is of importance for disease control. A calmodulin (CAL) gene-based TaqMan real-time PCR assay was developed for efficient detection and quantification of C. siamense, which reliably detected as low as 5 pg of genomic DNA and 12.8 fg (5800 copies) of target DNA. This method could specifically recognize all tested C. siamense isolates, while no amplification was observed in other closely related Colletotrichum species. The assay could still detect C. siamense in plant mixes, of which only 0.01% of the tissue was infected. A dynamic change in the amount of C. siamense population was observed during infection, suggesting that this real-time PCR assay can be used to monitor the fungal growth progression in the whole disease process. Moreover, the method enabled the detection of C. siamense in naturally infected and symptomless leaves of P. glabra trees in fields. Taken together, this specific TaqMan real-time PCR provides a rapid and accurate method for detection and quantification of C. siamense colonization in P. glabra, and will be useful for prediction of the disease to reduce the epidemic risk.