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20 pages, 4196 KiB  
Article
Postdigital Bystanding: Youth Experiences of Sexual Violence Workshops in Schools in England, Ireland, and Canada
by Jessica Ringrose, Debbie Ging, Faye Mishna, Betsy Milne, Tanya Horeck and Kaitlynn Mendes
Behav. Sci. 2025, 15(1), 81; https://doi.org/10.3390/bs15010081 (registering DOI) - 18 Jan 2025
Abstract
In this paper, we report on creative- and arts-based sexual violence and bystander intervention workshops we developed and researched in England, Ireland, and Canada, through evaluation surveys, observations, and focus group interviews with nearly 1200 young people (aged 13–18). Whist the young people [...] Read more.
In this paper, we report on creative- and arts-based sexual violence and bystander intervention workshops we developed and researched in England, Ireland, and Canada, through evaluation surveys, observations, and focus group interviews with nearly 1200 young people (aged 13–18). Whist the young people generally reported benefitting from the intervention, in the context of increasing use of digital technologies amongst youth, we explore the context-specific challenges they faced in learning about and being supported through bystander strategies across a wide range of diverse school spaces. We use the term postdigital bystanding to explicitly explore how teen’s digital networks are often connected to the school-based ‘real life’ peer group, in ways that complicate clear distinctions between online and offline, arguing that these postdigital dynamics have not yet been adequately considered in bystanding interventions. We analyse how the intersectional community, cultural, and identity-specific factors in particular schooling environments shape responses to bystanding in postdigital environments, including how factors of sexism, defensive masculinity, elitism, racism, and a reluctance to report digital issues played out in the responses to the workshops. Finally, following young people’s suggestions, we recommend that schools need to cultivate better safety and support strategies for youth in order to make postdigital bystander interventions more responsive and therefore effective in challenging and preventing sexual violence in society. Full article
(This article belongs to the Special Issue Perspectives on Violence and Sexual Harassment)
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Figure 1
<p>‘How to be an Active Bystander—the 5Ds’ slide.</p>
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<p>Scenario 2 slide.</p>
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<p>‘How can we Challenge Sexual and Gender-Based Violence’ post-it note activity slide.</p>
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<p>Examples of young people’s ‘Distract strategies’ (Hampshire, UK).</p>
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<p>‘How can we challenge sexual and gender based violence’ post-it note activity (Hampshire, England).</p>
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<p>Post-it notes for making schools a safer place.</p>
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<p>Post-it notes for listening and taking action.</p>
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<p>Post-it notes for education and raising awareness.</p>
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18 pages, 3812 KiB  
Article
The Stability-Indicating Ultra High-Performance Liquid Chromatography with Diode Array Detector and Tandem Mass Spectrometry Method Applied for the Forced Degradation Study of Ritlecitinib: An Appraisal of Green and Blue Metrics
by Jelena Kovačić, Daniela Amidžić Klarić, Nikša Turk, Željko Krznarić, Emma Riordan and Ana Mornar
Pharmaceuticals 2025, 18(1), 124; https://doi.org/10.3390/ph18010124 - 17 Jan 2025
Abstract
Background/Objectives: Janus kinase inhibitors open new horizons for small-molecule drugs in treating inflammatory bowel disease, with ritlecitinib demonstrating significant efficacy in clinical trials for ulcerative colitis and Crohn’s disease. Ritlecitinib, a second-generation JAK3 inhibitor, is a novel therapeutic agent for alopecia areata and [...] Read more.
Background/Objectives: Janus kinase inhibitors open new horizons for small-molecule drugs in treating inflammatory bowel disease, with ritlecitinib demonstrating significant efficacy in clinical trials for ulcerative colitis and Crohn’s disease. Ritlecitinib, a second-generation JAK3 inhibitor, is a novel therapeutic agent for alopecia areata and other autoimmune conditions. Methods: A new stability-indicating UHPLC-DAD-MS/MS method was developed, validated, and applied for a forced degradation study of ritlecitinib under ICH guidelines. Results: The method demonstrated high specificity, sensitivity (LOD: 0.04 µg/mL; LOQ: 0.14 µg/mL), precision (RSD ≤ 0.15%), and accuracy (99.9–100.3%). Forced degradation studies under acidic, basic, oxidative, thermal, and photolytic conditions revealed four novel degradation products. Basic degradation followed second-order kinetics, while oxidative degradation followed zero-order kinetics. Conclusions: The validated method reliably characterized ritlecitinib’s stability and degradation products, providing essential data for optimizing formulation, determining proper storage conditions, anticipating drug–excipient interactions, and ensuring quality control. The eco-friendliness and applicability of the developed forced degradation procedure were evaluated using various green and blue metric tools. Incorporating green analytical principles underscores its potential for sustainable pharmaceutical analysis. Full article
(This article belongs to the Special Issue Advances in Drug Analysis and Drug Development)
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Figure 1

Figure 1
<p>Structure of the irreversible Janus kinase 3 and tyrosine kinase inhibitor, ritlecitinib.</p>
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<p>Representative LC chromatograms of ritlecitinib samples (100 µg/mL): (<b>a</b>) control, (<b>b</b>) basic, and (<b>c</b>) oxidative degradation.</p>
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<p>Mass spectra data of ritlecitinib. (<b>a</b>) Full scan ESI-MS spectrum, showing the protonated molecular ion [M+H]<sup>+</sup> at <span class="html-italic">m</span>/<span class="html-italic">z</span> 286. (<b>b</b>) Product ion ESI-MS/MS spectrum of the protonated molecular ion [M+H]<sup>+</sup> (<span class="html-italic">m</span>/<span class="html-italic">z</span> 286), collision energy of 20 V (insert: proposed fragmentation pattern).</p>
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<p>Positive single scan ESI-MS spectra of degradation products: (<b>a</b>) Degradation Product 1—DP1 (basic hydrolysis), (<b>b</b>) Degradation Product 2—DP2 (basic hydrolysis), (<b>c</b>) Degradation Product 3—DP3 (basic hydrolysis/oxidative stress), and (<b>d</b>) Degradation Product 4—DP4 (oxidative stress).</p>
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<p>The MoGAPI score of ritlecitinib forced degradation protocol.</p>
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<p>The ComplexGAPI score of ritlecitinib forced degradation protocol.</p>
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<p>The AGREE score of ritlecitinib forced degradation protocol.</p>
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<p>The AGREEprep score of ritlecitinib forced degradation protocol.</p>
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<p>The BAGI score of ritlecitinib forced degradation protocol.</p>
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17 pages, 973 KiB  
Article
BiVO4-Based Systems Magnetron Sputtered with Silver Nanoparticles for the Artificial Photosynthesis Reaction
by Eva Naughton, Emerson C. Kohlrausch, Jesum Alves Fernandes and James A. Sullivan
Sustain. Chem. 2025, 6(1), 4; https://doi.org/10.3390/suschem6010004 - 17 Jan 2025
Abstract
The incorporation of Ag nanoparticles onto BiVO4 (a known H2O oxidising photocatalyst) through magnetron sputtering to form a composite was studied. ICP-OES results showed that the loading of Ag on BiVO4 was below 1% in all cases. UV-Vis DRS [...] Read more.
The incorporation of Ag nanoparticles onto BiVO4 (a known H2O oxidising photocatalyst) through magnetron sputtering to form a composite was studied. ICP-OES results showed that the loading of Ag on BiVO4 was below 1% in all cases. UV-Vis DRS and CO2-TPD analyses demonstrated that upon incorporation of Ag onto BiVO4, an increase in the extent of visible light absorption and CO2 adsorption was seen. TEM imaging showed the presence of Ag particles on the surface of larger BiVO4 particles, while XRD analysis provided evidence for some doping of Ag into BiVO4 lattices. The effect of the composite formation on the activity of the materials in the artificial photosynthesis reaction was significant. BiVO4 alone produces negligible amounts of gaseous products. However, the Ag-sputtered composites produce both CO and CH4, with a higher loading of Ag leading to higher levels of product formation. This reactivity is ascribed to the generation of a heterojunction in the composite material. It is suggested that the generation of holes in BiVO4 following photon absorption is used to provide protons (from H2O oxidation), and the decay of an SPR response on the Ag NPs provides hot electrons, which together with the protons reduce CO2 to produce CH4, CO, and adsorbed hydrocarbonaceous species. Full article
22 pages, 273 KiB  
Article
Retrospective Study of Chronic Coughing in Dogs in a Referral Centre in the UK: 329 Cases (2012–2021)
by Carla Asorey Blazquez, Ico Jolly Frahija, Arran Smith, Rachel Miller, Mayank Seth, Edgar Garcia Manzanilla and Ferran Valls Sanchez
Animals 2025, 15(2), 254; https://doi.org/10.3390/ani15020254 - 17 Jan 2025
Abstract
Chronic coughing is a common complaint in small animal medicine and it has an extensive differential diagnosis with very different treatment and prognosis. Coughing is considered chronic when it lasts at least 8 weeks. This retrospective study aimed to describe the most common [...] Read more.
Chronic coughing is a common complaint in small animal medicine and it has an extensive differential diagnosis with very different treatment and prognosis. Coughing is considered chronic when it lasts at least 8 weeks. This retrospective study aimed to describe the most common causes of chronic coughing in a population of dogs that presented to a referral hospital in England between January 2012 and December 2021. In addition, we aimed to evaluate if an association with signalment, weight, coughing characteristics, and/or concomitant clinical signs could be identified. A total of 329 dogs met the inclusion criteria. The most frequent diagnoses were airway collapse (102/329, 30.7%), chronic bronchitis (80/329, 24.3%), neoplasia (62/329, 18.8%), and infectious bronchopneumonia (54/329, 16.4%). Other diagnoses were also identified in a lower number of cases. Pomeranian, Chihuahua, and Yorkshire Terrier were over-represented breeds for airway collapse. No predictive factors were identified for chronic bronchitis. Lower body weight (odds ratio [OR] 0.92, 95% confidence interval [CI]: 0.90–0.95), non-productive (OR 14.3 CI 3.44–50) paroxysmal coughing (OR 4.9, 95%, CI: 2.2–11.0), and exercise intolerance (OR 3.3, 95%, CI: 1.7–6.3) increased the odds of airway collapse. Older dogs (OR 1.025, 95%, CI: 1.014–1.036), higher body weight (OR 1.048, 95%, CI: 1.018–1.080), lethargy (OR 5.1, 95%, CI: 1.5–17.7), haemoptysis (OR 8.6, 95%, CI: 1.9–38.4), weight loss (OR 4.0, 95%, CI: 1.1–15.3), and inappetence (OR 6.5, 95%, CI: 1.9–22.1) increased the odds of neoplasia. Productive coughing (OR 3.0, 95%, CI: 1.5–6) and nasal discharge (OR 4.1, 95%, CI: 1.4–11.9) were predictive factors of infectious bronchopneumonia. Younger age (OR 0.96, 95%, CI: 1.061–1.150), higher body weight (OR 1.097, 95%, CI: 1.037–1.161), and haemoptysis (OR 11.8, 95%, CI: 1.8–78.5), increased the odds of airway foreign body. Higher body weight (OR 1.105, 95%, CI: 1.061–1.150), older age (OR 1.041, 95%, CI: 1.022–1.061), and regurgitation were predictive factors of laryngeal paralysis. Epiglottic retroversion was associated with younger age (OR 0.969, 95%, CI: 0.943–0.994), dysphagia (OR 42.5, 95%, CI: 4.7–382.7), and regurgitation (OR 11.6, 95%, CI: 1.2–113.1). All the aforementioned findings are valuable for prioritising differential diagnoses and consequently increasing the efficacy of the diagnostic plan and prioritising tests, which becomes even more important in cases where financial constraints are present. Finally, an appropriate selection of diagnostics tools helps optimise veterinary resources. Full article
(This article belongs to the Section Veterinary Clinical Studies)
18 pages, 2526 KiB  
Article
Proteomics of the Dark-Ventral-Patch Sexual Signal in Male Red Deer
by Camilla Broggini, Paula V. Huertas-Abril, Alberto Membrillo, Eva de la Peña, Nieves Abril and Juan Carranza
Animals 2025, 15(2), 252; https://doi.org/10.3390/ani15020252 - 17 Jan 2025
Abstract
Sexual signals in animals encompass a variety of forms including visual, acoustic, and chemical signals that are fundamental for intra- and interspecific communication, including sexual selection processes. Among these, odor signals play a critical role. Chemical compounds involved in sexual signaling vary in [...] Read more.
Sexual signals in animals encompass a variety of forms including visual, acoustic, and chemical signals that are fundamental for intra- and interspecific communication, including sexual selection processes. Among these, odor signals play a critical role. Chemical compounds involved in sexual signaling vary in nature, with lipids and proteins being particularly important. In the male Iberian red deer (Cervus elaphus hispanicus), the dark ventral patch has been identified as a key sexual signal during mating competition, associated with specific chemical compounds deposited during urination. Hair plays a significant role in this signaling due to its ability to retain compounds on the scales of the hair cuticle. In this study, we used a shotgun proteomic approach to investigate whether the ventral patch hair retains proteins on its surface that could reveal metabolic and cell-signaling adaptations potentially related to reproductive activity. Characterization of the origin and functionality of the proteins found in the hair of the dark ventral patch of male red deer, and their relationship to distinct metabolic pathways, provides an initial understanding of the potential role of these compounds in chemical communication in red deer intrasexual competition for mates. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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Figure 1
<p>Sampling areas. The map highlights the geographical distribution of the hunting estates included in the study and located on the Iberian Peninsula: CCH, CR, ESC, TOR, VIL and VA in Andalusia, and CV and MAY in Extremadura, Spain.</p>
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<p>The red deer ventral proteome. (<b>A</b>) Contribution (%) of each red deer individual to the total identified protein counts. Clear gray was used for female samples (n = 18) and dark gray for male samples (n = 21); (<b>B</b>) major components of the red deer ventral proteomes.</p>
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<p>Differentially abundant proteins in the male red deer ventral dark patch. (<b>A</b>) A cluster heat map of proteomics profiles in males vs. control (females). Each row in the figure represents a protein and each column represents a sample (dark green: control samples; light green: male samples). The protein expression values are displayed on a color scale, with red indicating the highest upregulated levels and blue indicating the most downregulated levels. (<b>B</b>) Principal component analysis (PCA) plot representing proteomics data from the comparative analysis of control (female) and male groups. The plot displays two distinct clusters. (<b>C</b>) STRING analysis of proteomics data: (<b>c1</b>) Network statistics reporting data concerning the number of nodes and edges, the average node degree, the average local clustering coefficient, the expected number of edges and the protein–protein interaction (PPI) enrichment <span class="html-italic">p</span>-value. (<b>c2</b>) Reactome pathways analysis, showing the three most enriched pathways in the proteome of the male red deer ventral dark patch. (<b>c3</b>) Network interaction image showing nodes and edges between the proteins identified. The minimum required interaction score was 0.4 (medium confidence). The thickness of a line indicates the strength of the interaction between the proteins it connects.</p>
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<p>Functional analysis of protein–protein interaction (PPI): K-means clustering based on STRING database. Distribution of male dark ventral patch proteins among eight clusters suggested by STRING k-means analysis (default k-means clustering method).</p>
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<p>PANTHER Gene Ontology classification of proteins exclusively present in male red deer living in HC estates based on involvement in biological processes.</p>
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<p>PANTHER classification of proteins exclusively present in male red deer living in LC estates.</p>
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54 pages, 6031 KiB  
Article
(E)-1-(3-(3-Hydroxy-4-Methoxyphenyl)-1-(3,4,5-Trimethoxyphenyl)allyl)-1H-1,2,4-Triazole and Related Compounds: Their Synthesis and Biological Evaluation as Novel Antimitotic Agents Targeting Breast Cancer
by Gloria Ana, Azizah M. Malebari, Sara Noorani, Darren Fayne, Niamh M. O’Boyle, Daniela M. Zisterer, Elisangela Flavia Pimentel, Denise Coutinho Endringer and Mary J. Meegan
Pharmaceuticals 2025, 18(1), 118; https://doi.org/10.3390/ph18010118 - 17 Jan 2025
Viewed by 164
Abstract
Background/Objectives: The synthesis of (E)-1-(1,3-diphenylallyl)-1H-1,2,4-triazoles and related compounds as anti-mitotic agents with activity in breast cancer was investigated. These compounds were designed as hybrids of the microtubule-targeting chalcones, indanones, and the aromatase inhibitor letrozole. Methods: A panel of [...] Read more.
Background/Objectives: The synthesis of (E)-1-(1,3-diphenylallyl)-1H-1,2,4-triazoles and related compounds as anti-mitotic agents with activity in breast cancer was investigated. These compounds were designed as hybrids of the microtubule-targeting chalcones, indanones, and the aromatase inhibitor letrozole. Methods: A panel of 29 compounds was synthesized and examined by a preliminary screening in estrogen receptor (ER) and progesterone receptor (PR)-positive MCF-7 breast cancer cells together with cell cycle analysis and tubulin polymerization inhibition. Results: (E)-5-(3-(1H-1,2,4-triazol-1-yl)-3-(3,4,5-trimethoxyphenyl)prop-1-en-1-yl)-2-methoxyphenol 22b was identified as a potent antiproliferative compound with an IC50 value of 0.39 mM in MCF-7 breast cancer cells, 0.77 mM in triple-negative MDA-MB-231 breast cancer cells, and 0.37 mM in leukemia HL-60 cells. In addition, compound 22b demonstrated potent activity in the sub-micromolar range against the NCI 60 cancer cell line panel including prostate, melanoma, colon, leukemia, and non-small cell lung cancers. G2/M phase cell cycle arrest and the induction of apoptosis in MCF-7 cells together with inhibition of tubulin polymerization were demonstrated. Immunofluorescence studies confirmed that compound 22b targeted tubulin in MCF-7 cells, while computational docking studies predicted binding conformations for 22b in the colchicine binding site of tubulin. Compound 22b also selectively inhibited aromatase. Conclusions: Based on the results obtained, these novel compounds are suitable candidates for further investigation as antiproliferative microtubule-targeting agents for breast cancer. Full article
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Graphical abstract

Graphical abstract
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<p>Drugs for the treatment of breast cancer: SERMs (tamoxifen <b>1a</b>, 4-hydroxytamoxifen <b>1b</b>, endoxifen <b>1c</b>, norendoxifen <b>1d</b>), SERD fulvestrant <b>2</b>, PROTAC elacestrant <b>3</b>, ARV-471 <b>4</b>, aromatase inhibitors (exemestane <b>5</b>, letrozole <b>6</b>, and anastrozole <b>7</b>).</p>
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<p>Targeted therapies for breast cancer: CDK4/6 inhibitors palbociclib <b>8</b>, ribociclib <b>9</b>, and abemacicilib <b>10</b>, mTOR inhibitor everolimus <b>11</b>; PI3K inhibitor alpelisib <b>12</b>, AKT inhibitor capivasertib <b>13</b>; PARP inhibitors olaparib <b>14</b>, and talazoparib <b>15</b>.</p>
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<p>Antiproliferative chalcones and related compounds that target the colchicine binding site of tubulin: α-methylchalcones <b>16a–e</b>, O-arylchalcone <b>16f</b>, millepachine <b>17</b>, bischalcone <b>18</b>, combretastatins CA-4 <b>19a</b> and CA-1 <b>19b</b>, and phenstatin <b>19c</b>.</p>
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<p>Target structures <b>A</b> (chalcone-based) and <b>B</b> (indane-based) for synthesis.</p>
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<p>Preliminary cell viability data for Series 1: (<b>A</b>) compounds <b>22a–22g</b> and chalcone <b>20b</b> and Series 2: (<b>B</b>) compounds <b>23a–e</b> and chalcone <b>20b</b> in MCF-7 breast cancer cells. Cell proliferation of MCF-7 cells was determined with an alamarBlue assay (seeding density 2.5 × 10<sup>4</sup> cells/mL per well for 96-well plates). Compound concentrations of either 1 or 0.1 μM for 72 h were used to treat the cells (in triplicate) with control wells containing vehicle ethanol (1% <span class="html-italic">v</span>/<span class="html-italic">v</span>). The mean value ± SEM for three independent experiments is shown. The positive controls used are CA-4 and phenstatin (1.0 μM and 0.1 μM). Statistical analysis was performed using One-way ANOVA with the Sidak multiple comparison test (***, <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Preliminary cell viability data for (<b>A</b>) triazoles <b>26a–e</b> and related indanone <b>24a</b> and (<b>B</b>) imidazoles <b>27a–f</b>, <b>27h</b>, <b>27i</b> and related compounds <b>30</b> and <b>33b</b> in MCF-7 breast cancer cells. Cell proliferation of MCF-7 cells was determined with an alamarBlue assay (seeding density 2.5 × 10<sup>4</sup> cells/mL per well for 96-well plates). Compound concentrations of either 1 or 0.1 μM for 72 h were used to treat the cells (in triplicate) with control wells containing vehicle ethanol (1% <span class="html-italic">v</span>/<span class="html-italic">v</span>). The mean value ± SEM for three independent experiments is shown. The positive controls used were CA-4 and phenstatin (1.0 μM and 0.1 μM). Statistical test was performed using One-way ANOVA with Sidak multiple comparison test (***, <span class="html-italic">p</span> &lt; 0.001).</p>
Full article ">Figure 6 Cont.
<p>Preliminary cell viability data for (<b>A</b>) triazoles <b>26a–e</b> and related indanone <b>24a</b> and (<b>B</b>) imidazoles <b>27a–f</b>, <b>27h</b>, <b>27i</b> and related compounds <b>30</b> and <b>33b</b> in MCF-7 breast cancer cells. Cell proliferation of MCF-7 cells was determined with an alamarBlue assay (seeding density 2.5 × 10<sup>4</sup> cells/mL per well for 96-well plates). Compound concentrations of either 1 or 0.1 μM for 72 h were used to treat the cells (in triplicate) with control wells containing vehicle ethanol (1% <span class="html-italic">v</span>/<span class="html-italic">v</span>). The mean value ± SEM for three independent experiments is shown. The positive controls used were CA-4 and phenstatin (1.0 μM and 0.1 μM). Statistical test was performed using One-way ANOVA with Sidak multiple comparison test (***, <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Preliminary cell viability data for (<b>A</b>) triazoles <b>22b–d</b>, <b>22f</b>, <b>22g</b> and imidazole <b>23d</b> and (<b>B</b>) triazoles <b>26a–e</b> and imidazoles <b>27a</b>, <b>27b</b>, <b>27e</b>, <b>27f</b>, <b>27h</b> and <b>27i</b> in HL-60 cells. Cell proliferation of HL-60 cells was determined with an alamarBlue assay (seeding density 2.5 × 10<sup>4</sup> cells/mL per well for 96-well plates). Compound concentrations of either 1 or 0.1 μM for 72 h were used to treat the cells (in triplicate) with control wells containing vehicle ethanol (1% <span class="html-italic">v</span>/<span class="html-italic">v</span>). The mean value ± SEM for three independent experiments is shown. The positive control was CA-4 (1.0 μM and 0.1 μM).</p>
Full article ">Figure 7 Cont.
<p>Preliminary cell viability data for (<b>A</b>) triazoles <b>22b–d</b>, <b>22f</b>, <b>22g</b> and imidazole <b>23d</b> and (<b>B</b>) triazoles <b>26a–e</b> and imidazoles <b>27a</b>, <b>27b</b>, <b>27e</b>, <b>27f</b>, <b>27h</b> and <b>27i</b> in HL-60 cells. Cell proliferation of HL-60 cells was determined with an alamarBlue assay (seeding density 2.5 × 10<sup>4</sup> cells/mL per well for 96-well plates). Compound concentrations of either 1 or 0.1 μM for 72 h were used to treat the cells (in triplicate) with control wells containing vehicle ethanol (1% <span class="html-italic">v</span>/<span class="html-italic">v</span>). The mean value ± SEM for three independent experiments is shown. The positive control was CA-4 (1.0 μM and 0.1 μM).</p>
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<p>Heatmap for compound <b>22b</b> across cell lines in the NCI-60 cell screen. Heatmap for the antiproliferative activity of compound <b>22b</b> (NCI 788807), across the cell lines in the NCI-60 screen, using three different values: (growth-inhibitory effect, GI<sub>50</sub>; drug concentration at which the response is reduced by half, IC<sub>50</sub>; cytostatic effect, TGI; cytotoxic effect, LC<sub>50</sub>; concentration in molar). Color key for GI<sub>50</sub> and IC<sub>50</sub>: green is more sensitive, and red is less sensitive.</p>
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<p>Effect of compounds <b>22a</b> (<b>A</b>) and <b>22b</b> (<b>B</b>) on the cell viability of non-tumorigenic MCF-10A human mammary epithelial cells at 24, 48, and 72 h. Cells were treated with the compounds <b>22a</b> and <b>22b</b> at concentrations of 10 μM, 1 μM, 0.5 μM, and 0.4 μM for 24, 48, or 72 h. (<b>C</b>) shows a comparison of the cell viability of MCF-10A cells and MCF-7 cells when treated with compound <b>22b</b> for 72 h at concentrations of 10 μM, 1 μM, and 0.5 μM. Cell viability was expressed as a percentage of vehicle control (ethanol 1% (<span class="html-italic">v</span>/<span class="html-italic">v</span>)) and was determined by an alamarBlue assay (average ± SEM of three independent experiments). Two-way ANOVA (Bonferroni post-test) was used to test for statistical significance (*, <span class="html-italic">p</span> &lt; 0.05; **, <span class="html-italic">p</span> &lt; 0.01; ***, <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Compound (<b>A</b>) <b>22b</b>, (<b>B</b>) phenstatin <b>19c</b> induced apoptosis in a time-dependent manner in MCF-7 cells. Cells were treated with either vehicle control [0.1% ethanol (<span class="html-italic">v</span>/<span class="html-italic">v</span>)] or compound <b>22b</b> or phenstatin <b>19c</b> (1 μM) for 24, 48, and 72 h). The data shown for the control vehicle and phenstatin are as we previously reported [<a href="#B65-pharmaceuticals-18-00118" class="html-bibr">65</a>]. Cells were fixed and stained with PI, followed by analysis using flow cytometry. Cell cycle analysis was performed on histograms of gated counts per DNA area (FL2-A). The number of cells with &lt;2 N (sub-G<sub>1</sub>), 2 N (G<sub>0</sub>G<sub>1</sub>), and 4 N (G<sub>2</sub>/M) DNA content was determined with CellQuest software, BD CellQuest Pro. Values are represented as the mean ± SEM for three separate experiments. Two-way ANOVA (Bonferroni post-test) was used to test for statistical significance (*, <span class="html-italic">p</span> &lt; 0.05; **, <span class="html-italic">p</span> &lt; 0.01; ***, <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Compound <b>22b</b> induced apoptosis in (<b>A</b>) MCF-7 breast cancer cells and (<b>B</b>) MDA-MB-231 breast cancer cells. MCF-7 breast cancer cells (<b>A</b>) and MDA-MB-23 breast cancer cells (<b>B</b>) were treated with <b>22b</b> (0.1, 0.5, and 1.0 μM) or phenstatin (<b>19c</b>) (0.1 μM and 0.5 μM) or control vehicle (0.1% ethanol (<span class="html-italic">v</span>/<span class="html-italic">v</span>)). The data shown for the control vehicle and phenstatin are as we previously reported [<a href="#B65-pharmaceuticals-18-00118" class="html-bibr">65</a>]. The apoptotic cell content was determined by staining with Annexin V-FITC and PI. In each panel, the lower right quadrant shows Annexin-positive cells in the early apoptotic stage and the upper right shows both Annexin/PI-positive cells in late apoptosis/necrosis. The lower left quadrant shows cells that are negative for both PI and Annexin V-FITC, and the upper left shows PI cells that are necrotic.</p>
Full article ">Figure 11 Cont.
<p>Compound <b>22b</b> induced apoptosis in (<b>A</b>) MCF-7 breast cancer cells and (<b>B</b>) MDA-MB-231 breast cancer cells. MCF-7 breast cancer cells (<b>A</b>) and MDA-MB-23 breast cancer cells (<b>B</b>) were treated with <b>22b</b> (0.1, 0.5, and 1.0 μM) or phenstatin (<b>19c</b>) (0.1 μM and 0.5 μM) or control vehicle (0.1% ethanol (<span class="html-italic">v</span>/<span class="html-italic">v</span>)). The data shown for the control vehicle and phenstatin are as we previously reported [<a href="#B65-pharmaceuticals-18-00118" class="html-bibr">65</a>]. The apoptotic cell content was determined by staining with Annexin V-FITC and PI. In each panel, the lower right quadrant shows Annexin-positive cells in the early apoptotic stage and the upper right shows both Annexin/PI-positive cells in late apoptosis/necrosis. The lower left quadrant shows cells that are negative for both PI and Annexin V-FITC, and the upper left shows PI cells that are necrotic.</p>
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<p>Compound <b>22b</b> depolymerizes the microtubule network of MCF-7 breast cancer cells. MCF-7 breast cancer cells were treated with (<b>A</b>) vehicle control [1% ethanol (<span class="html-italic">v</span>/<span class="html-italic">v</span>)], (<b>B</b>) paclitaxel (1 μM), (<b>C</b>) phenstatin (<b>19c</b>) (1 μM), or (<b>D</b>) compound <b>22b</b> (10 μM) for 16 h. Cells were preserved in ice-cold methanol and then stained with mouse monoclonal anti-α-tubulin–FITC–antibody (clone DM1A) (green), Alexa Fluor 488 dye, and counterstained with DAPI (blue). The micrograph images were obtained with Leica SP8 confocal microscopy utilizing Leica application suite X software. Representative confocal images of three separate experiments are shown. The scale bar indicates 25 μm.</p>
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<p>Inhibition of tubulin polymerization in vitro by compound <b>22b</b>. Tubulin polymerization assay for triazole compound <b>22b</b> at 10 μM and 30 μM concentration, together with control compounds paclitaxel (polymeriser) (10 μM) and phenstatin (depolymeriser) <b>19c</b> (10 μM). DMSO (1% <span class="html-italic">v</span>/<span class="html-italic">v</span>) was used in the vehicle control. Purified bovine tubulin and guanosine-5′-triphosphate (GTP) were initially mixed at 4 °C in a 96-well plate; the polymerization reaction was then initiated by warming the solution from 4 to 37 °C. The progress of the tubulin polymerization reaction at 37 °C was monitored at 340 nm in a Spectramax 340PC spectrophotometer at 30 s intervals for 60 min. Fold inhibition of tubulin polymerization can be calculated from the Vmax value for each reaction. The data shown for the control vehicle and phenstatin are as we previously reported [<a href="#B65-pharmaceuticals-18-00118" class="html-bibr">65</a>].</p>
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<p>Docking of compounds <b>22b</b> in the colchicine binding site of tubulin. Overlay of the X-ray structure of tubulin co-crystallized with DAMA-colchicine (PDB entry 1SA0, [<a href="#B116-pharmaceuticals-18-00118" class="html-bibr">116</a>]) on the best-ranked docked poses of <span class="html-italic">(S)-</span><b>22b</b> and <span class="html-italic">(R)-</span><b>22b</b>. Ligands are rendered as tubes and amino acids as lines. Tubulin amino acids and DAMA-colchicine are colored by atom type; the novel compounds are colored green. The atoms are colored by element type, carbon = grey, hydrogen = white, oxygen = red, nitrogen = blue, sulfur = yellow. Key amino acid residues are labeled, and multiple residues are hidden to enable a clearer view.</p>
Full article ">Scheme 1
<p>Synthesis of (<span class="html-italic">E</span>)-1-(3-aryl)-1-(3,4,5-trimethoxyphenyl)allyl)-1<span class="html-italic">H</span>-1,2,4-triazoles <b>22a–g</b> (Series 1) and (<span class="html-italic">E</span>)-1-(3-(aryl)-1-(3,4,5-trimethoxyphenyl)allyl)-1<span class="html-italic">H</span>-imidazoles <b>23a–e</b> (Series 2): reagents and conditions (<b>a</b>): KOH, methanol, 20 °C (27–87%) (<b>b</b>): NaBH<sub>4</sub>, MeOH/THF, 1 h, 20 °C (85–100%); (<b>c</b>) <span class="html-italic">p</span>-TSA, 1,2,4-triazole, toluene, microwave, 4 h (30–76%); (<b>d</b>) CDI, dry ACN, reflux, 1 h (26–45%).</p>
Full article ">Scheme 2
<p>Synthesis of 1-(3-aryl-4,5,6-trimethoxy-2,3-dihydro-1<span class="html-italic">H</span>-inden-1-yl)-1<span class="html-italic">H</span>-1,2,4-triazoles <b>26a–e</b> (Series 3) and 1-(3-aryl-4,5,6-trimethoxy-2,3-dihydro-1<span class="html-italic">H</span>-inden-1-yl)-1<span class="html-italic">H</span>-imidazoles <b>27a–i</b> (Series 4). Scheme reagents and conditions: (<b>a</b>) TFA, 120 °C, 10 min microwave (44–96%); (<b>b</b>) NaBH<sub>4</sub>, MeOH/THF (1:1), 0–20 °C (43–100%); (<b>c</b>) <span class="html-italic">p</span>-TSA, 1,2,4-triazole, toluene, microwave, 4 h (30–54%); (<b>d</b>) CDI, dry acetonitrile, reflux, 3 h (4–70%).</p>
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<p>Synthesis of 1-((1<span class="html-italic">E</span>,4<span class="html-italic">E</span>)-1,5-bis(3,4,5-trimethoxyphenyl)penta-1,4-dien-3-yl)-1<span class="html-italic">H</span>-imidazole <b>30</b>. Reagents and conditions: (<b>a</b>): Acetone, EtOH, NaOH (10%, aqueous), 30 min, 20 °C (68%); (<b>b</b>): NaBH<sub>4</sub>, MeOH/THF, 1 h, 20 °C (92%); (<b>c</b>) CDI, dry ACN, 3 h, reflux (27%).</p>
Full article ">Scheme 4
<p>Synthesis of (<span class="html-italic">E</span>)-3-(anthracen-9-yl)-1-(4-iodophenyl)allyl)-1<span class="html-italic">H</span>-imidazole (<b>33a</b>) and (<span class="html-italic">E</span>)-3-(anthracen-9-yl)-1-(4-pyridyl))allyl)-1<span class="html-italic">H</span>-imidazole (<b>33b</b>): reagents and conditions: (<b>a</b>): KOH, methanol, 20 °C (49–82%) (<b>b</b>): NaBH<sub>4</sub>, MeOH/THF, 1 h, 20 °C (78–98%); (<b>c</b>) CDI, dry ACN, reflux, 1 h (5–58%).</p>
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16 pages, 2021 KiB  
Article
Anthoteibinenes F–Q: New Sesquiterpenes from the Irish Deep-Sea Coral Anthothela grandiflora
by Stine S. H. Olsen, Sam Afoullouss, Ezequiel Cruz Rosa, Ryan M. Young, Mark Johnson, A. Louise Allcock and Bill. J. Baker
Mar. Drugs 2025, 23(1), 44; https://doi.org/10.3390/md23010044 - 17 Jan 2025
Viewed by 108
Abstract
New technology has opened opportunities for research and exploration of deep-water ecosystems, highlighting deep-sea coral reefs as a rich source of novel bioactive natural products. During our ongoing investigation of the chemodiversity of the Irish deep sea and the soft coral Anthothela grandiflora, [...] Read more.
New technology has opened opportunities for research and exploration of deep-water ecosystems, highlighting deep-sea coral reefs as a rich source of novel bioactive natural products. During our ongoing investigation of the chemodiversity of the Irish deep sea and the soft coral Anthothela grandiflora, we report 12 unreported cadinene-like functionalized sesquiterpenes, anthoteibinenes F–Q. The metabolites were isolated using both bioassay- and 1H NMR-guided approaches. One-/two-dimensional NMR spectroscopy and high-resolution mass spectrometry were used for structure elucidation, while a combination of NOESY NMR experiments, GIAO NMR calculations coupled with DP4+ probabilities measures, and ECD comparisons were incorporated to propose relative and absolute configurations of the anthoteibinenes. The metabolites were screened against the Respiratory Syncytial Virus (RSV), ESKAPE pathogens, five Candida albicans strains, and one strain of C. auris. Full article
(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments III)
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<p>Anthoteibinenes F–Q, sesquiterpenes from the Irish deep-sea coral <span class="html-italic">Anthothela grandiflora</span>.</p>
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<p>Key COSY (bold bonds) and HMBC (arrows) correlations establishing the planar structure of anthoteibinene F (<b>1</b>).</p>
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<p>Wire frame plot of anthoteibinene M (<b>8</b>).</p>
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<p>Stereochemical analysis of anthoteibinene F (<b>1</b>). (<b>A</b>) NOESY spectrum of <b>1</b>, with key NOE correlations highlighted. (<b>B</b>) Conformers of <b>1</b> found using OPLS4 highlighting two main conformer types. (<b>C</b>) DP4+ probability of two possible diastereomers of <b>1</b>. (<b>D</b>) Experimental ECD (black) spectrum vs. calculated spectra for 2<span class="html-italic">R</span>,6<span class="html-italic">S</span>,7<span class="html-italic">R</span> (red/upper broken trace) and 2<span class="html-italic">S</span>,6<span class="html-italic">R</span>,7<span class="html-italic">S</span> (blue/lower broken trace).</p>
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<p><b>(Top</b>) DP4+ probability of 7<span class="html-italic">R</span>,10<span class="html-italic">R</span> vs. 7<span class="html-italic">R</span>,10<span class="html-italic">S</span> of <b>3</b> and <b>10</b>. (<b>Bottom</b>) Experimental ECD (black) and predicted ECD (7<span class="html-italic">R</span>,10<span class="html-italic">R</span>, blue) and (7<span class="html-italic">R</span>,10<span class="html-italic">S</span>, red) spectra of <b>3</b> and <b>10</b>.</p>
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<p>(<b>Top</b>) NOESY correlations establishing relative configuration of <b>7</b> and <b>9</b>, respectively, displayed on low-energy conformers. (<b>Bottom</b>) Experimental ECD (black) spectrum vs. calculated spectra for respective enantiomers (red/blue broken trace).</p>
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16 pages, 697 KiB  
Review
Novel Micro-Ribonucleic Acid Biomarkers for Early Detection of Type 2 Diabetes Mellitus and Associated Complications—A Literature Review
by Sara Ahmed, Haroon Adnan, Maryam A. Khawaja and Alexandra E. Butler
Int. J. Mol. Sci. 2025, 26(2), 753; https://doi.org/10.3390/ijms26020753 - 17 Jan 2025
Viewed by 177
Abstract
Type 2 diabetes mellitus (T2DM) is one of the most widespread chronic diseases globally, with its prevalence expected to rise significantly in the years ahead. Previous studies on risk stratification for T2DM identify certain biomarkers, including glycated hemoglobin (HbA1c), oral glucose tolerance testing [...] Read more.
Type 2 diabetes mellitus (T2DM) is one of the most widespread chronic diseases globally, with its prevalence expected to rise significantly in the years ahead. Previous studies on risk stratification for T2DM identify certain biomarkers, including glycated hemoglobin (HbA1c), oral glucose tolerance testing (OGTT), fructosamine, and glycated albumin, as key indicators for predicting the onset and progression of T2DM. However, these traditional markers have been shown to lack sensitivity and specificity and their results are difficult to analyze due to non-standardized interpretation criteria, posing significant challenges to an accurate and definitive diagnosis. The strict measures of these traditional markers may not catch gradual increases in blood sugar levels during the early stages of diabetes evolution, as these might still fall within acceptable glycemic parameters. Recent advancements in research have suggested novel micro ribonucleic acid (miRNA) as circulatory molecules that can facilitate the early detection of prediabetic conditions in high-risk groups and potentially enable prevention of the progression to T2DM. This capability makes them a very powerful tool for potentially improving population health, enhancing outcomes for many patients, and reducing the overall burden of T2DM. These promising biomarkers are small, noncoding RNA involved in the regulation of many cellular functions that have a hand in the metabolic activities of cells, making them a very useful and relevant biomarker to explore for the diagnosis and risk stratification of T2DM. This review analyzes the current literature, outlining the occurrence of miRNAs in prediabetic and diabetic individuals and their implications in predicting dysglycemic disorders. Full article
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<p>MicroRNA expression in diabetic complications. Created using BioRender.com [<a href="#B122-ijms-26-00753" class="html-bibr">122</a>].</p>
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14 pages, 4800 KiB  
Article
The Potential of Sitka Spruce Bark as an Alternative to Peat Casing for Mushroom (Agaricus bisporus) Production
by Gabrielle Young, Helen Grogan, Eoghan Corbett, Brian W. McGuinness, Michael T. Gaffney, Saoirse Tracy, Olaf Schmidt and Lael Walsh
Horticulturae 2025, 11(1), 100; https://doi.org/10.3390/horticulturae11010100 - 17 Jan 2025
Viewed by 216
Abstract
White button mushrooms are an important crop globally, and due to the role of peat in current cultivation practices, the industry is under increasing pressure to find suitable alternatives. Peat functions as “casing”, a surface layer that, amongst other functions, provides available water [...] Read more.
White button mushrooms are an important crop globally, and due to the role of peat in current cultivation practices, the industry is under increasing pressure to find suitable alternatives. Peat functions as “casing”, a surface layer that, amongst other functions, provides available water to the fungal mycelium and is considered essential for mushroom growth. This research aimed to determine the potential of bark as an alternative casing material and its suitability for commercial mushroom production. Two experiments were conducted, comparing two types of commercially available peat casing with bark-based casings. The bark casing in Experiment A was found to be statistically similar to the peat casing in terms of yield and quality. The two bark casings in Experiment B failed to produce a 1st flush of mushrooms, and total yields were significantly lower compared to the peat casings, highlighting the fact that the consistency of the bark material across both experiments was variable. There were several issues associated with the bark casing, which included water stress and cropping delays, all of which would be unacceptable from a commercial perspective. Further research is required to refine bark-based casing, focusing on a better consistency of the bark feedstock and reduction of contamination risk. This work contributes to ongoing research and development to address the dependency of mushroom production on peat. Full article
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<p>Flow chart summarising key details and approximate timeline of the mushroom cropping process, ±2 days.</p>
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<p>Boxplot displaying the yield of mushrooms per tonne of compost over three flushes for each casing treatment as recorded in Experiment (<b>A</b>) (left) and Experiment (<b>B</b>) (right). Median and interquartile ranges displayed. Treatments are bulk casing (bP), fine peat casing (fP) and bark-based casing alternatives (B5 and B10).</p>
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<p>Stacked bar chart displaying the cumulative total yield of mushrooms per tonne of compost over three flushes for each casing treatment as recorded in Experiment (<b>A</b>) (left) and Experiment (<b>B</b>) (right). Treatments are bulk casing (bP), fine peat casing (fP) and bark-based casing alternatives (B5 and B10).</p>
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<p>Line plots displaying the mean average moisture content of casing treatments throughout the experimental period, as recorded in (<b>A</b>) (top) and (<b>B</b>) (bottom). Treatments were commercial bulk peat casing (bP), fine peat casing (fP) and bark-based casing alternatives (B5 and B10).</p>
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<p>Box plot displaying the L (lightness) value of mushrooms grown in Experiment A on each casing material in each growth flush, with median and interquartile ranges displayed. Treatments are commercial bulk peat casing (bP), fine peat casing (fP) and bark-based casing (B5).</p>
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<p>Observed presence of wild fungi. (<b>a</b>) Fruiting bodies, possibly <span class="html-italic">Parasola</span>, on B5 casing treatment. (<b>b</b>) Photographs of the fruiting bodies during the 1st flush of Experiment A. Light microscope image of spores isolated from contaminating fungi.</p>
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<p>Photographs showing the two different types of bark utilised in this study. These images are representative of the general appearance and particle size in Experiment A (<b>a</b>) and Experiment B (<b>b</b>).</p>
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13 pages, 593 KiB  
Article
Agronomic Performance of European Pear Cultivars in Different Training Systems in the Highland Region of Southern Brazil
by Alex Felix Dias, Sabrina Baldissera, Alberto Ramos Luz, Augusto Schütz Ferreira, Bruno Dalazen Machado, Bruno Pirolli, Renaldo Borges de Andrade Júnior, Joel de Castro Ribeiro, Daiana Petry Rufato, Aike Anneliese Kretzschmar, Amauri Bogo and Leo Rufato
Agriculture 2025, 15(2), 194; https://doi.org/10.3390/agriculture15020194 - 16 Jan 2025
Viewed by 274
Abstract
This study aimed to evaluate the vegetative, productive, and fruit quality parameters of the European pear cultivars ‘Rocha’ and ‘Santa Maria’ under the training systems of Tall Spindle, with branches bent at an angle of 45° (Tall Spindle—45°) and 90° (Tall Spindle—90°) to [...] Read more.
This study aimed to evaluate the vegetative, productive, and fruit quality parameters of the European pear cultivars ‘Rocha’ and ‘Santa Maria’ under the training systems of Tall Spindle, with branches bent at an angle of 45° (Tall Spindle—45°) and 90° (Tall Spindle—90°) to the leader, and Bi-axis. The evaluation was conducted over the 2016/2017 to 2022/2023 growing seasons in the highland region of southern Brazil. Both Tall Spindle systems significantly improved the yield and productive efficiency compared to the Bi-axis system, with ‘Santa Maria’ showing superior performance under Tall Spindle—90°. While ‘Rocha’ exhibited no significant differences between Tall Spindle systems, it benefited from better vigor control and reduced biennial bearing when trained under the Bi-axis system. Fruit quality parameters were consistent across training systems, indicating Tall Spindle—90° as an optimal choice for productivity and stability in ‘Santa Maria’. These results emphasize the adaptability and efficiency of training systems for pear orchard management. Full article
(This article belongs to the Section Crop Production)
38 pages, 6229 KiB  
Article
Wind–Wave Misalignment in Irish Waters and Its Impact on Floating Offshore Wind Turbines
by Thomas Shanahan and Breiffni Fitzgerald
Energies 2025, 18(2), 372; https://doi.org/10.3390/en18020372 - 16 Jan 2025
Viewed by 272
Abstract
This study examined the impact of wind–wave misalignment on floating offshore wind turbines (FOWTs) in Irish waters, analysing average weather and extreme events, including hurricane conditions. Using the ERA5 reanalysis dataset validated against Irish Marine Data Buoy Observation Network measurements, the results showed [...] Read more.
This study examined the impact of wind–wave misalignment on floating offshore wind turbines (FOWTs) in Irish waters, analysing average weather and extreme events, including hurricane conditions. Using the ERA5 reanalysis dataset validated against Irish Marine Data Buoy Observation Network measurements, the results showed a satisfactory accuracy with an average wind speed error of 0.54 m/s and a strong correlation coefficient of 0.92. Wind–wave misalignment was found to be inversely correlated with wind speed (correlation coefficient: 0.41), with minimum misalignment occurring approximately seven hours after a change in wind direction. The study revealed that misalignment could exceed 30 during hurricanes, contradicting standard assumptions of alignment under extreme conditions. The investigation highlighted that in western coastal areas, average misalignment could reach 57.95, while sheltered Irish Sea regions experienced lower values, such as 23.06. Numerical simulations confirmed that these misalignment events amplified side-to-side turbine deflections significantly. This research underscores the need to incorporate misalignment effects into industry testing standards and suggests that current methodologies may underestimate fatigue loads by up to 50%. This work emphasizes improved design and testing protocols for FOWTs in complex marine environments and highlights the suitability of ERA5 for climate analysis in Ireland. Full article
(This article belongs to the Special Issue Wind Turbine and Wind Farm Flows)
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<p>Increase in Ireland’s potential wind resources with the use of floating wind turbines [<a href="#B3-energies-18-00372" class="html-bibr">3</a>].</p>
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<p>Heat maps created using the Copernicus toolbox. (<b>a</b>) Average annual wave height. (<b>b</b>) Average annual wind speed.</p>
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<p>Red asterisks indicate locations of 129 ERA5 data points located around the Irish Coast.</p>
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<p>Wind turbulence data across Ireland.</p>
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<p>(<b>Left</b>) Map indicating the location of weather buoys around Ireland. (<b>Right</b>) A third-generation Irish weather buoy weighing over 6 tonnes [<a href="#B38-energies-18-00372" class="html-bibr">38</a>].</p>
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<p>Correlation plots for data at buoy M2.</p>
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<p>(<b>Left</b>) Misalignment around Ireland examining bias. (<b>Right</b>) Instantaneous magnitude of misalignment.</p>
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<p>An Examination of mean wind speed across Ireland.</p>
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<p>(<b>Left</b>) Rounded absolute misalignment. (<b>Right</b>) Geographical areas sectored by misalignment.</p>
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<p>Examining the relationship between misalignment and wind speed.</p>
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<p>Misalignment with regard to sign convention.</p>
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<p>(<b>Left</b>) Examination of wave direction, displaying the location of the Rockall Trough. (<b>Right</b>) Standard deviation of directional wave data.</p>
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<p>A display of steadily increasing wave period from east to west across Irish waters.</p>
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<p>Average wind direction around Ireland.</p>
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<p>Comparison of misalignment distribution of all areas.</p>
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<p>Comparison of wave height distribution of Areas F (<b>Left</b>) and G (<b>Right</b>).</p>
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<p>Histograms of wind speed around Ireland maintaining steady distribution and shape.</p>
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<p>Misalignment in storm/hurricane conditions in Irish waters.</p>
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<p>(<b>a</b>) Asterisk in the image denotes the location of the data point selected for the examination of misalignment and approaching weather systems. (<b>b</b>) Graph showing the results of time-shifting the mean wave direction with regards to misalignment.</p>
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<p>The effect of time shifting wave direction on misalignment for a point in the Irish Sea.</p>
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<p>Illustrations of the NREL 5-MW wind turbine on the OC3-Hywind spar [<a href="#B49-energies-18-00372" class="html-bibr">49</a>].</p>
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<p>Comparing areas of greatest and least misalignment across Ireland: (<b>a</b>) fore–aft deflection, (<b>b</b>) side-to-side deflection.</p>
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<p>Asterisks indicate the most likely locations to result in turbine tower resonance issues.</p>
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<p>Comparison of aligned and misaligned wave loading conditions, by the metrics of fore–aft deflection (<b>a</b>) and side-to-side deflection (<b>b</b>) in “Storm 1” conditions.</p>
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<p>Comparison of aligned and misaligned wave loading conditions, by the metrics of fore–aft deflection (<b>a</b>) and side-to-side deflection (<b>b</b>) in “Storm 2” conditions.</p>
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28 pages, 602 KiB  
Article
Alaria esculenta, Ulva lactuca, and Palmaria palmata as Potential Functional Food Ingredients for the Management of Metabolic Syndrome
by Emer Shannon and Maria Hayes
Foods 2025, 14(2), 284; https://doi.org/10.3390/foods14020284 - 16 Jan 2025
Viewed by 216
Abstract
Hypertension, type 2 diabetes (T2D), and obesity raise an individual’s risk of suffering from diseases associated with metabolic syndrome (MS). In humans, enzymes that play a role in the prevention and development of MS include angiotensin converting enzyme (ACE-1) associated with hypertension, α-amylase [...] Read more.
Hypertension, type 2 diabetes (T2D), and obesity raise an individual’s risk of suffering from diseases associated with metabolic syndrome (MS). In humans, enzymes that play a role in the prevention and development of MS include angiotensin converting enzyme (ACE-1) associated with hypertension, α-amylase associated with T2D, and lipase linked to the development of obesity. Seaweeds are a rich source of bioactives consisting of proteins/peptides, polysaccharides, and lipids. This study examined the potential of seaweed-derived bioactives from Alaria esculenta, Ulva lactuca, and Palmaria palmata as inhibitors of ACE-1, α-amylase, and lipase. In vitro enzyme inhibitory assays were used to quantify the bioactivity of the seaweed extracts and compare their half-maximal inhibitory (IC50) values to recognised positive control enzyme inhibitory drugs captopril© (an ACE-1 inhibitor), acarbose (an α-amylase inhibitor), and orlistat (a lipase inhibitor). Three seaweed extracts displayed enzyme inhibitory activities equal to, or more effective than, the reference positive control drugs. These were P. palmata peptides (ACE-1 IC50 94.29 ± 3.07 µg/mL, vs. captopril© 91.83 ± 2.68 µg/mL); A. esculenta polyphenol extract (α-amylase IC50 147.04 ± 9.72 µg/mL vs. acarbose 185.67 ± 12.48 µg/mL, and lipase IC50 106.21 ± 6.53 µg/mL vs. orlistat 139.74 ± 9.33 µg/mL); and U. lactuca polysaccharide extract (α-amylase IC50 168.06 ± 10.53 µg/mL vs. acarbose 185.67 ± 12.48 µg/mL). Proximate analysis also revealed that all three seaweeds were a good source of protein, fibre, and polyunsaturated essential fatty acids (PUFAs). These findings highlight the potential of these seaweeds in the management of diseases associated with MS and as foods. Full article
10 pages, 814 KiB  
Study Protocol
Enlightening Nursing Care: A Protocol for a Multicenter Observational Study Measuring Nursing Work in Hospital Settings
by Annamaria Bagnasco, Marco Di Nitto, Ilaria Marcomini, Rosaria Alvaro, Loreto Lancia, Duilio Fiorenzo Manara, Laura Rasero, Gennaro Rocco, Valeria Caponnetto, Manuele Cesare, Yari Longobucco, Francesco Zaghini, Paolo Iovino, Alessandra Burgio, Paolo Landa, Milko Zanini, Maurizio Zega, Giancarlo Cicolini, Walter Sermeus, Jonathan Drennan, John M. Welton, Beatrice Mazzoleni and Loredana Sassoadd Show full author list remove Hide full author list
Healthcare 2025, 13(2), 167; https://doi.org/10.3390/healthcare13020167 - 16 Jan 2025
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Abstract
Background: Rising costs and demands for improved quality of care present complex challenges for existing healthcare systems. The strain on healthcare resources is exacerbated by the increasing complexity of patient conditions. The Diagnosis-Related Group (DRG) system classifies inpatients according to clinical and [...] Read more.
Background: Rising costs and demands for improved quality of care present complex challenges for existing healthcare systems. The strain on healthcare resources is exacerbated by the increasing complexity of patient conditions. The Diagnosis-Related Group (DRG) system classifies inpatients according to clinical and treatment criteria, controls healthcare expenditures, and ensures the sustainability of procedures. The cost of nursing care is included in the DRG system in the same way as other fixed costs of hospital care, but the amount of nursing care provided for the same DRG can vary widely. This study, which is based on this protocol, will aim to assess the variability of nursing costs within and across DRGs and to measure how much variability in nursing care is explained by DRGs by comparing nursing care delivery in acute care hospitals with the DRG reimbursement system in Italy. It is necessary to develop a specific protocol to ensure systematic and consistent data collection at the national level. Methods: A multicenter retrospective cross-sectional study will be conducted. A random sample of five public Italian hospitals will be enrolled. Patients included in medical or surgical DRGs, hospitalized and discharged in 2022 will be included. Data will be collected retrospectively from two sources: hospital discharge records and nursing records. Inferential statistics will be used to assess the variability of nursing time and costs across hospitals and DRGs. Nursing costs will be determined by several factors, including time spent on nursing activities and the hourly wages of nursing staff. The time needed to complete each activity will be estimated by a convenience sample of nurses from the hospitals included in this study. The annual salary of nurses will be used to calculate the nursing cost per minute, multipled by the amount of time spent per each nursing activity. The cost per patient per day of hospitalization will be calculated. Conclusions: The results of this study will shed light on the variation in nursing care across different DRGs. This understanding will guide recommendations for optimizing healthcare resource allocation and enhancing the efficiency of the DRG system in Italy. Full article
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<p>Study phases.</p>
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21 pages, 1912 KiB  
Article
Unravelling the Digestibility and Structure–Function Relationship of Lentil Protein Through Germination and Molecular Weight Fractionation
by Armin Mirzapour-Kouhdasht, Samaneh Shaghaghian, Marjan Majdinasab, Jen-Yi Huang and Marco Garcia-Vaquero
Foods 2025, 14(2), 272; https://doi.org/10.3390/foods14020272 - 16 Jan 2025
Viewed by 354
Abstract
This study explores for the first time the impact of a 6-day germination process on the structure (FTIR), antioxidant activity, nutritional/safety attributes (ACE-I inhibitory activity, digestibility, and cytotoxicity), and functional properties of fractions of variable molecular weight (W > 5 kDa; 3 kDa [...] Read more.
This study explores for the first time the impact of a 6-day germination process on the structure (FTIR), antioxidant activity, nutritional/safety attributes (ACE-I inhibitory activity, digestibility, and cytotoxicity), and functional properties of fractions of variable molecular weight (W > 5 kDa; 3 kDa < MW < 5 kDa; and MW < 3 kDa) isolated from proteins extracted from lentils. FTIR results indicated a substantial increase in β-sheet contents during germination. The digestibility of proteins increased from day 0 (16.32–17.04%) to day 6 of germination (24.92–26.05%) with variable levels of digestibility depending on their MW. ACE-I inhibitory activity improved during germination in all fractions, reaching IC50 values of 0.95, 0.83, and 0.69 mg/mL after 6 days of germination. All antioxidant activities analyzed notably increased, particularly in low-MW fractions (MW < 3 kDa). The functional properties of low-MW fractions were also the most promising, displaying the highest water and fat binding capacities and emulsifying and foaming capacities but lower foaming and emulsifying stability compared to high-MW fractions. Cytotoxicity tests on L929 cells revealed the slight adverse effects of low-MW fractions during germination. This study provides insights into the enhanced nutritional and functional attributes of lentil proteins following germination, emphasizing their potential application in functional foods. Full article
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Graphical abstract

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<p>The evolution of lentil seeds during the germination process over a 6-day period.</p>
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<p>A schematic flow diagram illustrating the experimental design followed during this study.</p>
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<p>FTIR spectra of protein isolates generated from lentil seeds during germination (days 0–6). Results were recorded three times for each sample.</p>
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<p>Cytotoxicity of different MW fractions achieved from protein isolates from lentils during process of germination (days 0–6) using L929 cell lines. Different uppercase letters indicate statistically significant differences (<span class="html-italic">p</span> &lt; 0.05) in cytotoxicity between fractions of different MW within same germination day. Lowercase letters indicate statistically significant (<span class="html-italic">p</span> &lt; 0.05) differences in cytotoxicity between different germination days at same MW. Data are shown as average of three replicates.</p>
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<p>Antioxidant activities: (<b>a</b>) DPPH (%), (<b>b</b>) Fe chelating (%), (<b>c</b>) hydroxyl radical (%), and (<b>d</b>) FRAP (A) activities of different MW fractions achieved from protein isolates from lentils during process of germination (days 0–6). Different uppercase letters indicate statistically significant differences (<span class="html-italic">p</span> &lt; 0.05) in antioxidant activity between fractions of different MW within same germination day. Lowercase letters indicate statistically significant (<span class="html-italic">p</span> &lt; 0.05) differences in antioxidant activity between different germination days at same MW. Data are shown as average of two replicates.</p>
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18 pages, 240 KiB  
Article
Cognitive Stimulation Therapy (CST): Exploring Perspectives of Trained Practitioners on the Barriers and Facilitators to the Implementation of CST for People Living with Dementia
by Michelle E. Kelly, Saoirse Byrne, Roisin Lacey, Antoine Lemercier and Caoimhe Hannigan
Disabilities 2025, 5(1), 5; https://doi.org/10.3390/disabilities5010005 - 15 Jan 2025
Viewed by 485
Abstract
Dementia is recognised as a disability under the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD). People with disabilities like dementia have the right to access specialised health and social care services, including interventions that support independence and community participation. [...] Read more.
Dementia is recognised as a disability under the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD). People with disabilities like dementia have the right to access specialised health and social care services, including interventions that support independence and community participation. Cognitive Stimulation Therapy (CST) is an evidence-based psychosocial intervention that improves cognition, communication, confidence, and quality of life for people living with dementia, but an implementation gap means that CST is often not available. This study examines whether trained CST practitioners implemented CST, their perceptions of the acceptability and efficacy of CST, whether the perceived acceptability and efficacy of CST predicted implementation, and practitioners’ opinions on the barriers and facilitators to CST implementation. A mixed-methods approach was used, with 62 participants (91.9% female). Although 95% of participants were trained to deliver CST, 45.2% did not facilitate CST groups. Statistical analysis showed that perceived efficacy significantly predicted both the likelihood of running CST groups (p = 0.006) and the number of groups delivered (p = 0.01). Thematic analysis of qualitative data identified the three key themes of ‘resources’, ‘awareness and education’, and ‘acceptability of CST’. Overall, the results show that while CST is acceptable and deemed highly effective, resources and staffing often impede implementation. The results are discussed in the context of prioritising the rights of people with disabilities and recommendations are made on improving access to evidence-based support. Full article
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