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30 pages, 3038 KiB  
Article
Starch-Assisted Eco-Friendly Synthesis of ZnO Nanoparticles: Enhanced Photocatalytic, Supercapacitive, and UV-Driven Antioxidant Properties with Low Cytotoxic Effects
by Roumaissa Djafarou, Ouarda Brahmia, Soumia Haya, Ertugrul Sahmetlioglu, Fatma Kılıç Dokan and Tarek Hidouri
Int. J. Mol. Sci. 2025, 26(2), 859; https://doi.org/10.3390/ijms26020859 (registering DOI) - 20 Jan 2025
Abstract
This study presents an efficient and environmentally sustainable synthesis of ZnO nanoparticles using a starch-mediated sol-gel approach. This method yields crystalline mesoporous ZnO NPs with a hexagonal wurtzite structure. The synthesized nanoparticles demonstrated remarkable multifunctionality across three critical applications. In photocatalysis, the ZnO [...] Read more.
This study presents an efficient and environmentally sustainable synthesis of ZnO nanoparticles using a starch-mediated sol-gel approach. This method yields crystalline mesoporous ZnO NPs with a hexagonal wurtzite structure. The synthesized nanoparticles demonstrated remarkable multifunctionality across three critical applications. In photocatalysis, the ZnO NPs exhibited exceptional efficiency, achieving complete degradation of methylene blue within 15 min at pH 11, significantly surpassing the performance of commercial ZnO. Under neutral pH conditions, the nanoparticles effectively degraded various organic dyes, including methylene blue, rhodamine B, and methyl orange, following pseudo-first-order kinetics. The methylene blue degradation process was aligned with the Langmuir–Hinshelwood model, emphasizing their advanced catalytic properties. For supercapacitor applications, the ZnO NPs attained a high specific capacitance of 550 F/g at 1 A/g, underscoring their potential as energy storage solutions. Additionally, the nanoparticles demonstrated strong UV-induced antiradical activity, with an EC50 of 32.2 μg/mL in DPPH assays. Notably, the cytotoxicity evaluation revealed an LC50 of 1648 μg/mL, indicating excellent biocompatibility. This study highlights a sustainable approach for the synthesis of multifunctional ZnO NPs that offers effective solutions for environmental remediation, energy storage, and biomedical applications. Full article
(This article belongs to the Special Issue Molecular Advances in Semiconductor Materials)
18 pages, 3245 KiB  
Article
Weizmannia coagulans BC99 Attenuates Oxidative Stress Induced by Acute Alcoholic Liver Injury via Nrf2/SKN-1 Pathway and Liver Metabolism Regulation
by Ying Wu, Cheng Li, Yinyin Gao, Jie Zhang, Yao Dong, Lina Zhao, Yuwan Li and Shaobin Gu
Antioxidants 2025, 14(1), 117; https://doi.org/10.3390/antiox14010117 - 20 Jan 2025
Abstract
Acute alcoholic liver injury (AALI) remains a significant global health concern, primarily driven by oxidative stress. This study investigated the protective mechanisms of Weizmannia coagulans BC99 against alcohol-induced oxidative stress using a dual model in rats and Caenorhabditis elegans. In rats, excessive alcohol [...] Read more.
Acute alcoholic liver injury (AALI) remains a significant global health concern, primarily driven by oxidative stress. This study investigated the protective mechanisms of Weizmannia coagulans BC99 against alcohol-induced oxidative stress using a dual model in rats and Caenorhabditis elegans. In rats, excessive alcohol was predominantly metabolized via the CYP2E1 pathway, leading to severe oxidative stress. However, intervention with BC99 suppressed CYP2E1 expression and enhanced antioxidant enzyme activities through the Nrf2/SKN-1 pathway, thereby alleviating oxidative stress. Additionally, BC99 treatment elevated glutamate and aspartate levels while reducing glycerate and glucose, which collectively increased glutathione levels and mitigated oxidative stress triggered by glucose metabolism disorders. In C. elegans, BC99 reduced excessive ROS by upregulating Nrf2/skn-1, daf-16, and their downstream antioxidant genes, consequently alleviating the biotoxicity associated with alcohol-induced oxidative damage. The protective effects of BC99 were markedly diminished in the skn-1 mutant (GR2245) and daf-16 mutant (CF1038), further confirming the pivotal roles of SKN-1 and DAF-16 pathways in BC99-mediated antioxidant protection. Taken together, these findings reveal that BC99 mitigates alcohol-induced oxidative stress by activating the Nrf2/SKN-1 pathway and regulating liver metabolites to eliminate excess ROS, thereby providing a theoretical basis for the application of probiotics in preventing acute alcoholic liver injury. Full article
(This article belongs to the Special Issue Alcohol-Induced Oxidative Stress in Health and Disease, 2nd Edition)
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Figure 1

Figure 1
<p>BC99 improved the liver injury of AALI rats. (<b>A</b>) Experiment design, (<b>B</b>) changes in body weight of rats, (<b>C</b>) plasma ALT level, (<b>D</b>) plasma AST level, (<b>E</b>) plasma LDH level, (<b>F</b>) plasma TBA level, (<b>G</b>) liver H&amp;E staining, magnification 200×, (<b>H</b>) liver H&amp;E staining, magnification 400×. The blue arrow represents disordered cell arrangement, while the red arrow represents cell necrosis. ### <span class="html-italic">p</span> &lt; 0.001 vs. the NC group. * <span class="html-italic">p</span> &lt; 0.05, *** <span class="html-italic">p</span> &lt; 0.001 vs. the AD group.</p>
Full article ">Figure 2
<p>BC99 reduced liver oxidative stress injury in AALI rats. (<b>A</b>) Liver ADH activity. (<b>B</b>) Liver ALDH activity. (<b>C</b>) Liver CYP2E1 level. (<b>D</b>) Liver SOD activity. (<b>E</b>) Liver GSH content. (<b>F</b>) Liver MDA content. ## <span class="html-italic">p</span> &lt; 0.01, ### <span class="html-italic">p</span> &lt; 0.001 vs. the NC group. ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. the AD group.</p>
Full article ">Figure 3
<p>BC99 altered liver metabolites in AALI rats. (<b>A</b>) PCA analysis. (<b>B</b>) OPLS-DA score scatter plot (NC vs. AD). (<b>C</b>) OPLS-DA score scatter plot (AD vs. AH). (<b>D</b>) Volcanic diagram of differential metabolites (NC vs. AD). (<b>E</b>) Volcanic diagram of differential metabolites (AD vs. AH). (<b>F</b>) Heat map of the top 50 differential metabolites (NC vs. AD). (<b>G</b>) Heat map of the top 50 differential metabolites (AD vs. AH).</p>
Full article ">Figure 4
<p>Main biomarkers and metabolic networks of BC99 intervening AALI (AD vs. AH). (<b>A</b>) Metabolic pathway analysis of differential metabolites. Each bubble represents a metabolic pathway. The larger the bubble, the more important the pathway. (<b>B</b>) Correlation analysis of differential metabolites, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01. (<b>C</b>) The network of key metabolic pathways. Different colors indicate metabolites that were upregulated (blue) or downregulated (red) in the AH group compared with the AD group. Solid arrow indicates single process. Dotted arrow indicates multiple processes. Bar graphs show the levels of important differential metabolites, # <span class="html-italic">p</span> &lt; 0.05 vs. the NC group. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 vs. the AD group.</p>
Full article ">Figure 5
<p>BC99 enhanced the expression of antioxidant-related genes in AALI rats. (<b>A</b>) Expression of genes related to alcohol metabolism. (<b>B</b>) Expression of genes related to Nrf2 pathway. ### <span class="html-italic">p</span> &lt; 0.001 vs. the NC group. * <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 vs. the AD group.</p>
Full article ">Figure 6
<p>Spearman correlation analysis of differential metabolites. (<b>A</b>) Spearman correlation analysis between liver differential metabolites and intestinal flora. (<b>B</b>) Spearman correlation analysis of differential metabolites and phenotypes. * <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>
Full article ">Figure 7
<p>BC99 enhanced the levels of antioxidant-related genes and enzymes in N2 nematodes. (<b>A</b>) Relative fluorescence intensity of ROS in N2 nematodes. (<b>B</b>) Typical images of ROS in N2 nematodes (scale bar 20 μm). (<b>C</b>) SOD activity. (<b>D</b>) GSH content. (<b>E</b>) CAT activity. (<b>F</b>) MDA content. (<b>G</b>) Relative gene expression of antioxidant related genes. ## <span class="html-italic">p</span> &lt; 0.01, ### <span class="html-italic">p</span> &lt; 0.001 vs. the Con group. ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. the Mod group.</p>
Full article ">Figure 8
<p>BC99 significantly attenuated the antioxidant stress resistance of GR2245 and CF1038 mutants. (<b>A</b>) GR2245 mutant survival curve. (<b>B</b>) GR2245 mutant average life. (<b>C</b>) CF1038 mutant survival curve. (<b>D</b>) CF1038 mutant average life. ## <span class="html-italic">p</span> &lt; 0.01 vs. the Con group.</p>
Full article ">
39 pages, 4703 KiB  
Article
Mechanisms of the Photomechanical Response in Thin-Film Dye-Doped Glassy Polymers
by Zoya Ghorbanishiadeh, Ankita Bhuyan, Bojun Zhou, Morteza Sheibani Karkhaneh and Mark G. Kuzyk
Polymers 2025, 17(2), 254; https://doi.org/10.3390/polym17020254 - 20 Jan 2025
Abstract
This work aims to determine the mechanism of the photomechanical response of poly(Methyl methacrylate) polymer doped with the photo-isomerizable dye Disperse Red 1 using the non-isomerizable dye Disperse Orange 11 as a control to isolate photoisomerization. Samples are free-standing thin films with thickness [...] Read more.
This work aims to determine the mechanism of the photomechanical response of poly(Methyl methacrylate) polymer doped with the photo-isomerizable dye Disperse Red 1 using the non-isomerizable dye Disperse Orange 11 as a control to isolate photoisomerization. Samples are free-standing thin films with thickness that is small compared with the optical skin depth to assure uniform illumination and photomechanical response throughout their volume, which differentiates these studies from most others. Polarization-dependent measurements of the photomechanical stress response are used to deconvolute the contributions of angular hole burning, molecular reorientation and photothermal heating. While photo-isomerization of dopant molecules is commonly observed in dye-doped polymers, the shape changes of a molecule might not couple strongly to the host polymer through steric mechanical interactions, thus not contributing substantially to a macroscopic shape change. To gain insights into the effectiveness of such mechanical coupling, we directly probe the dopant molecules using dichroism measurements simultaneously while measuring the photomechanical response and find mechanical coupling to be small enough to make photothermal heating—mediated by the transfer of optical energy as heat to the polymer—the dominant mechanism. We also predict the fraction of light energy converted to mechanical energy using a model whose parameters are thermodynamic material properties that are measured with independent experiments. We find that in the thin-film geometry, these dye-doped glassy polymers are as efficient as any other material but their large Young’s modulus relative to other organic materials, such as liquid crystal elastomers, makes them suitable in applications that require mechanically strong materials. The mechanical properties and the photomechanical response of thin films are observed to be significantly different than in fibers, suggesting that the geometry of the material and surface effects might play an important role. Full article
(This article belongs to the Special Issue Advanced Stimuli-Responsive Polymer Composites)
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Figure 1

Figure 1
<p>Molecular structure of (<b>a</b>) the trans state of Disperse Red 1 (DR1), (<b>b</b>) the cis form, and (<b>c</b>) Disperse Orange 11 (DO11) [<a href="#B2-polymers-17-00254" class="html-bibr">2</a>].</p>
Full article ">Figure 2
<p>Typical photomechanical stress response as observed in a film as a function of time and a fit to the theory given by Equations (<a href="#FD2-polymers-17-00254" class="html-disp-formula">2</a>) and (<a href="#FD3-polymers-17-00254" class="html-disp-formula">3</a>).</p>
Full article ">Figure 3
<p>Measured temperature-dependent stress at constant sample length and with no light applied of DR1 and DO11 thin films (points) and a fit of the data (curves) to Equation (<a href="#FD4-polymers-17-00254" class="html-disp-formula">4</a>).</p>
Full article ">Figure 4
<p>The apparatus used for the intensity and polarization-dependent response measurement. M: Mirror, P B/S: Polarized beam-splitter, G: Glass slide, P: Polarizer, <math display="inline"><semantics> <mrow> <mi>λ</mi> <mo>/</mo> <mn>2</mn> </mrow> </semantics></math>: Half-wave plate, L: Lens, Sh: Shutter, C: Clamp, S: Sample, F: Force sensor, PM1, PM2, PM3: Power meters.</p>
Full article ">Figure 5
<p>The force measurement setup and sample, which is placed at the intersection of the three beams as diagrammed in <a href="#polymers-17-00254-f004" class="html-fig">Figure 4</a>.</p>
Full article ">Figure 6
<p>Photomechanical stress response of DR1 and DO11 thin films for horizontal and perpendicular polarization of light as a function of intensity at infinite time, when all processes have come into equilibrium.</p>
Full article ">Figure 7
<p>The ratio of the photomechanical stress due to angular hole burning and heating.</p>
Full article ">Figure 8
<p>(<b>top</b>) Absorbance parallel and perpendicular to the pump beam polarizations in DR1- and DO11-doped PMMA thin films as a function of time with increasing pump intensity. (<b>bottom</b>) A close-up of the data for one on–off cycle showing a fast process associated with angular hole burning and two slow processes, which includes molecular reorientation.</p>
Full article ">Figure 8 Cont.
<p>(<b>top</b>) Absorbance parallel and perpendicular to the pump beam polarizations in DR1- and DO11-doped PMMA thin films as a function of time with increasing pump intensity. (<b>bottom</b>) A close-up of the data for one on–off cycle showing a fast process associated with angular hole burning and two slow processes, which includes molecular reorientation.</p>
Full article ">Figure 9
<p>Measured order parameter of DR1- and DO11-doped PMMA thin films as a function of time. Time is a proxy for intensity as shown in the pump power plots on the bottom part of the top graph of <a href="#polymers-17-00254-f008" class="html-fig">Figure 8</a>. (<b>top</b>) Order parameter relative to the sample’s long axis and (<b>bottom</b>) order parameter relative to the pump beam’s polarization axis.</p>
Full article ">Figure 10
<p>Order parameter of DR1- and DO11-doped PMMA thin films as a function of intensity. (<b>top</b>) Order parameter relative to the sample’s long axis and (<b>bottom</b>) order parameter relative to the pump’s polarization axis for vertically (vertical lines) and horizontally polarized (horizontal lines) pump. The data markers at <math display="inline"><semantics> <mrow> <mi>I</mi> <mo>=</mo> <mn>0</mn> </mrow> </semantics></math> include the initial measurement before the start of the experiment, as well as all the order parameters measured when the pump light is blocked prior to increasing intensity (the <math display="inline"><semantics> <mrow> <mi>I</mi> <mo>=</mo> <mn>0</mn> </mrow> </semantics></math> wells of the pump power are plotted in the upper portion of <a href="#polymers-17-00254-f008" class="html-fig">Figure 8</a>).</p>
Full article ">Figure 10 Cont.
<p>Order parameter of DR1- and DO11-doped PMMA thin films as a function of intensity. (<b>top</b>) Order parameter relative to the sample’s long axis and (<b>bottom</b>) order parameter relative to the pump’s polarization axis for vertically (vertical lines) and horizontally polarized (horizontal lines) pump. The data markers at <math display="inline"><semantics> <mrow> <mi>I</mi> <mo>=</mo> <mn>0</mn> </mrow> </semantics></math> include the initial measurement before the start of the experiment, as well as all the order parameters measured when the pump light is blocked prior to increasing intensity (the <math display="inline"><semantics> <mrow> <mi>I</mi> <mo>=</mo> <mn>0</mn> </mrow> </semantics></math> wells of the pump power are plotted in the upper portion of <a href="#polymers-17-00254-f008" class="html-fig">Figure 8</a>).</p>
Full article ">Figure 11
<p>Change in the order parameter in DR1- and DO11-doped PMMA thin films relative to the order parameter of the pristine sample as a function of the pump intensity. This includes the order parameter change induced by the light and the accumulated change in the order parameter from past exposures. (<b>top</b>) Order parameter relative to the long axis of the sample and (<b>bottom</b>) order parameter relative to the pump beam’s polarization axis.</p>
Full article ">Figure 12
<p>Fractional change in the order parameter relative to the order parameter just prior to the pump being turned on as a function of pump intensity in DR1- and DO11-doped PMMA thin films. (<b>top</b>) Fractional order parameter change relative to the sample’s long axis and (<b>bottom</b>) relative to the pump axis for both vertically and horizontally polarized pump light.</p>
Full article ">Figure 13
<p>Long-term time evolution of the fractional order parameter change <span class="html-italic">when the pump is off</span> relative to the order parameter of the pristine sample as a function of the intensity of the pump prior to the initial measurement at <math display="inline"><semantics> <mrow> <mi>t</mi> <mo>=</mo> <mn>0</mn> </mrow> </semantics></math> in DR1- and DO11-doped PMMA thin films. (<b>top</b>) Fractional order parameter change relative to the sample’s long axis and (<b>bottom</b>) relative to the pump axis for both vertically and horizontally polarized pump light.</p>
Full article ">Figure 14
<p>Long-term time evolution of the fractional order parameter change as a function of the pump intensity in DR1- and DO11-doped PMMA thin films. (<b>top</b>) Fractional order parameter change relative to the sample’s long axis and (<b>bottom</b>) relative to the pump axis for both vertically and horizontally polarized pump light.</p>
Full article ">Figure 15
<p>The measured stress versus strain in DR1- and DO11-doped PMMA thin films at room temperature. The plot shows 5 separate runs for each material. The initial slope below a strain of 0.003 is due to system backlash. Young’s modulus is determined from the slope of the average of the 5 runs above a strain of 0.004.</p>
Full article ">Figure 16
<p>Amplitudes <math display="inline"><semantics> <msub> <mi>σ</mi> <mn>1</mn> </msub> </semantics></math> (<b>top</b>) and <math display="inline"><semantics> <msub> <mi>σ</mi> <mn>2</mn> </msub> </semantics></math> (<b>bottom</b>) for DR1- and DO11-Doped PMMA thin films as a function of pump intensity for both vertically and horizontally polarized pump. The negative stress of the fast process given by <math display="inline"><semantics> <msub> <mi>σ</mi> <mn>1</mn> </msub> </semantics></math> implies that the length increases under light exposure and the increase gets larger with intensity. <math display="inline"><semantics> <msub> <mi>σ</mi> <mn>2</mn> </msub> </semantics></math> is positive, implying that for the slow process the sample contracts when pumped with light.</p>
Full article ">Figure 17
<p>The vertical and horizontal lines (representing the pump polarization relative to the vertical) show the predicted heating contribution to the photomechanical response for DO11 and DR1 thin films using the theory given by Equation (<a href="#FD9-polymers-17-00254" class="html-disp-formula">9</a>). The time constants <math display="inline"><semantics> <mrow> <msub> <mi>t</mi> <mn>1</mn> </msub> <mrow> <mo>(</mo> <mi>I</mi> <mo>)</mo> </mrow> </mrow> </semantics></math> at each intensity used in the model are the measured ones in <a href="#polymers-17-00254-f0A1" class="html-fig">Figure A1</a> in <a href="#app1-polymers-17-00254" class="html-app">Appendix A</a>. The width of the bands show one standard deviation band of the magnitude of the fast component of the experimentally determined intensity dependent photomechanical constant, which is determined from a quadratic fit of the stress data shown in the top graph in <a href="#polymers-17-00254-f016" class="html-fig">Figure 16</a>.</p>
Full article ">Figure 18
<p>The vertical and horizontal lines (representing the pump polarization relative to the vertical) show the predicted heating contribution to the photomechanical response for DO11 and DR1 thin films using <math display="inline"><semantics> <msub> <mi>t</mi> <mn>1</mn> </msub> </semantics></math> for the time constant as a function of intensity using the semi-empirical theory given by Equation (<a href="#FD12-polymers-17-00254" class="html-disp-formula">12</a>). The one-standard-deviation bands show the experimentally determined intensity-dependent photomechanical constant using a fit of the stress data to a quadratic function in the intensity, as shown in the top graph in <a href="#polymers-17-00254-f016" class="html-fig">Figure 16</a>.</p>
Full article ">Figure 19
<p>The vertical and horizontal lines (representing the pump polarization relative to the vertical) show the predicted heating contribution to the photomechanical response for DO11 and DR1 thin film using <math display="inline"><semantics> <mrow> <msub> <mi>t</mi> <mn>2</mn> </msub> <mrow> <mo>(</mo> <mi>I</mi> <mo>)</mo> </mrow> </mrow> </semantics></math> as the time constant in the model given by Equation (<a href="#FD9-polymers-17-00254" class="html-disp-formula">9</a>). The bands show the experimentally determined intensity-dependent photomechanical constant determined by the fit of the stress data to a quadratic function in the intensity, as shown in the bottom graph of <a href="#polymers-17-00254-f016" class="html-fig">Figure 16</a>.</p>
Full article ">Figure 20
<p>The vertical and horizontal lines (representing the pump polarization relative to the vertical) show the predicted heating contribution to the photomechanical response for DO11 and DR1 thin film using <math display="inline"><semantics> <mrow> <msub> <mi>t</mi> <mn>2</mn> </msub> <mrow> <mo>(</mo> <mi>I</mi> <mo>)</mo> </mrow> </mrow> </semantics></math> as the time constant in the semi-empirical model given by Equation (<a href="#FD12-polymers-17-00254" class="html-disp-formula">12</a>). The one-standard-deviation error bands show the experimentally determined intensity-dependent photomechanical constant determined from the fit of the stress data to a quadratic function in the intensity, as shown in the bottom graph of <a href="#polymers-17-00254-f016" class="html-fig">Figure 16</a>.</p>
Full article ">Figure A1
<p>The fast time constant <math display="inline"><semantics> <msub> <mi>t</mi> <mn>1</mn> </msub> </semantics></math> of the photomechanical response for DR1- and DO11-doped PMMA thin films as a function of intensity. The inset shows the average time constant over the whole intensity range for each material. (<b>top</b>) Vertically and (<b>bottom</b>) horizontally polarized pump.</p>
Full article ">Figure A2
<p>The slow time constant <math display="inline"><semantics> <msub> <mi>t</mi> <mn>2</mn> </msub> </semantics></math> of the photomechanical response for DR1- and DO11-doped PMMA thin films as a function of intensity. The inset shows the average time constant over the whole intensity range for each material. (<b>top</b>) Vertically and (<b>bottom</b>) horizontally polarized pump.</p>
Full article ">Figure A2 Cont.
<p>The slow time constant <math display="inline"><semantics> <msub> <mi>t</mi> <mn>2</mn> </msub> </semantics></math> of the photomechanical response for DR1- and DO11-doped PMMA thin films as a function of intensity. The inset shows the average time constant over the whole intensity range for each material. (<b>top</b>) Vertically and (<b>bottom</b>) horizontally polarized pump.</p>
Full article ">Figure A3
<p>The fast relaxation time constant <math display="inline"><semantics> <msub> <mi>t</mi> <mn>3</mn> </msub> </semantics></math> for DR1- and DO11-doped PMMA thin films as a function of intensity. The inset shows the average time constant over the whole intensity range for each material. (<b>top</b>) Vertically and (<b>bottom</b>) horizontally polarized pump.</p>
Full article ">Figure A4
<p>The slow relaxation time constant <math display="inline"><semantics> <msub> <mi>t</mi> <mn>4</mn> </msub> </semantics></math> for DR1- and DO11-doped PMMA thin films as a function of intensity. The inset shows the average time constant over the whole intensity range for each material. (<b>top</b>) Vertically and (<b>bottom</b>) horizontally polarized pump.</p>
Full article ">
13 pages, 1820 KiB  
Article
Adenovirus-Neutralizing and Infection-Promoting Activities Measured in Serum of Human Brain Cancer Patients Treated with Oncolytic Adenovirus Ad5-∆24.RGD
by Ida H. van der Meulen-Muileman, Joana Amado-Azevedo, Martine L. M. Lamfers, Anne Kleijn, Sander Idema, David P. Noske, Clemens M. F. Dirven and Victor W. van Beusechem
Int. J. Mol. Sci. 2025, 26(2), 854; https://doi.org/10.3390/ijms26020854 (registering DOI) - 20 Jan 2025
Abstract
Oncolytic adenoviruses derived from human serotype 5 (Ad5) are being developed to treat cancer. Treatment efficacy could be affected by pre-existing or induced neutralizing antibodies (NAbs), in particular in repeat administration strategies. Several oncolytic adenoviruses that are currently in clinical development have modified [...] Read more.
Oncolytic adenoviruses derived from human serotype 5 (Ad5) are being developed to treat cancer. Treatment efficacy could be affected by pre-existing or induced neutralizing antibodies (NAbs), in particular in repeat administration strategies. Several oncolytic adenoviruses that are currently in clinical development have modified fiber proteins to increase their infectivity. One example is Ad5-∆24.RGD, which carries a cyclic RGD peptide insert in the fiber protein to allow cell entry via integrins. The effect of anti-Ad5 NAbs on anticancer efficacy could be different for oncolytic adenoviruses with RGD-modified fibers than for unmodified Ad5-based viruses. Here, we determine pre-existing and elicited NAb titers in the serum of patients with glioblastoma who were treated by delivering Ad5-∆24.RGD to the tumor and to the surrounding tumor-infiltrated brain. We show that intracranial infusion of Ad5-∆24.RGD induced mainly neutralization of adenovirus native tropism. Infection of cells with RGD-modified virus was significantly less affected. In cerebrospinal fluid, neutralizing activity against RGD-mediated infection remained very low. Thus, the RGD-mediated alternative cell entry route allowed to bypass pre-existing and induced anti-Ad5 neutralization. Interestingly, in the course of these experiments, we discovered that the serum of most humans promotes the uptake of RGD-modified adenovirus in human cells. The until now unidentified infection-stimulating factor seems distinct from serum proteins known to promote Ad5 infection. Together, our work supports the utility of RGD-modified oncolytic adenoviruses for the treatment of cancer in humans. Since these viruses hardly induced neutralization, they seem particularly suitable for repeat administration treatments. Full article
(This article belongs to the Section Molecular Oncology)
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Figure 1

Figure 1
<p>Adenovirus neutralizing antibody titers in the serum of patients with recurrent glioblastoma undergoing treatment by intracranial infusion of oncolytic adenovirus Ad5-∆24.RGD. Titers are derived from the serum dilution titration experiments shown in <a href="#app1-ijms-26-00854" class="html-app">Figures S1 and S2</a>. The assay detection limit (4) is shown in all panels (dashed line). Samples with undetectable NAb titer are shown at arbitrary positions below the detection limit. (<b>A</b>) Pre-treatment titers of antibodies that neutralize AdLuc and AdLucRGD. (<b>B</b>) Comparison of titers before and at 2 and 4 weeks after Ad5-∆24.RGD infusion, for antibodies that neutralize AdLuc. (<b>C</b>) Comparison of titers before and at 2 and 4 weeks after Ad5-∆24.RGD infusion, for antibodies that neutralize AdLucRGD. (<b>D</b>) Titers of antibodies that neutralize AdLuc and AdLucRGD, 4 weeks after Ad5-∆24.RGD infusion. Individual data points for all 19 patients are shown in all panels, with medians in panels A and D indicated with red lines. Statistical tests used are paired two-way <span class="html-italic">t</span>-test in (<b>A</b>,<b>D</b>) and One-Way ANOVA on matched data, with Tukey’s multiple comparisons test in (<b>B</b>,<b>C</b>). ns, not significant; *, <span class="html-italic">p</span> &lt; 0.05; **, <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Reduced adenovirus NAb titers in cerebrospinal fluid. Titers of antibodies that neutralize AdLuc and AdLucRGD were determined in the CSF of eight glioblastoma patients who had been treated 4 weeks before with oncolytic adenovirus Ad5-∆24.RGD. Measured titers are compared with matching serum samples from the same patients collected on the same day. The graph shows the individual data (dots) with medians (red lines). The assay detection limit (4) is indicated by the dashed line. Statistical differences were tested using One-Way ANOVA on matched data, with Tukey’s multiple comparisons test. <span class="html-italic">p</span>-values for compared groups are shown.</p>
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<p>Identification of blood samples that promote adenovirus vector-mediated transduction. (<b>A</b>) Serum dilution titration experiment with AdLucRGD on samples from patient #8. (<b>B</b>) Peak transduction was reached with AdLuc (upper panel) or AdLucRGD (lower panel) for all patient serum samples relative to controls without human serum. (<b>C</b>) Peak transduction with AdLucRGD that is reached in the presence of plasma from 14 healthy donors relative to controls without human plasma (mean ± SD). In panel C, samples are ranked according to increasing transduction efficiency. In all panels, the reference line at 200% transduction that was used as an arbitrary threshold to score positive samples is shown (dashed line).</p>
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<p>Comparison of RGD-modified adenovirus infection-promoting activities in human blood products. Blood samples from glioblastoma patients who were treated with oncolytic adenovirus were used to isolate serum or plasma. Part of these samples were heat-inactivated before use. The dilution series of these samples were tested for the transduction efficiency of AdLucRGD on A549 cells. Data shown are the peak transductions reached for all samples at any dilution, relative to controls without human serum (dots) and means per group (lines). Matched samples from eight patients were used. Plasma samples were available from only four of these patients. Therefore, the unbalanced datasets were compared by a Restricted Maximum Likelihood (REML) Mixed-effects model on matched data. Only the significant difference identified by Tukey’s multiple comparisons test is shown.</p>
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<p>Separation of RGD-modified adenovirus neutralizing and infection-promoting activities in human serum by size exclusion and IgG depletion. Sera from patient #7 collected 3 (<b>A</b>,<b>C</b>,<b>E</b>) and 4 (<b>B</b>,<b>D</b>,<b>E</b>) days after oncolytic adenovirus infusion were separated over a Sepharose 6B column. (<b>A</b>,<b>B</b>) Individual fractions were tested for their influence on A549 cell transduction by AdLucRGD. Collected fractions were tested at 5-fold dilution, in comparison to AdLucRGD without serum (100%) and AdLucRGD with unfractionated 5-fold diluted serum (input). Data are the means + SD from a single experiment performed in triplicate. (<b>C</b>,<b>D</b>) Full AdLucRGD transduction neutralization analysis of selected pooled low, medium and high-MW fractions in comparison to unfractionated serum (input). Fractions were selected on the basis of the elution profiles observed in panels A and B. Data are the means ± SD from a single experiment performed in triplicate. (<b>E</b>) Transduction neutralization analysis of pooled medium MW fractions (i.e., day-3 fractions 14 and 15; day-4 fractions 15 and 16) before and after IgG depletion, tested at 8-fold dilution (i.e., peak transduction observed in panels (<b>C</b>,<b>D</b>)). Data are the means + SD of two experiments performed in quintuplicate.</p>
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22 pages, 5103 KiB  
Article
Brussels Chicory Enhances Exhaustive Aerobic Exercise Performance and Post-Exercise Recovery, Possibly Through Promotion of Lactate Oxidation: A Pilot Randomized, Single-Blind, Placebo-Controlled, Two-Way Crossover Study
by Yihui Mao, Junhao Huang, Shuangshuang Li, Guanyu Chen, Yushi Du, Mengxi Kang, Shasha Zhu, Wenyu Zhang, Qiuhui Xu, Yihan Wang, Wenhua Ling, Xijuan Luo and Dongliang Wang
Nutrients 2025, 17(2), 365; https://doi.org/10.3390/nu17020365 - 20 Jan 2025
Abstract
Background: Brussels chicory affluent in phenolic acids could inhibit atherosclerosis; however, its effects on exercise performance and post-exercise recovery are unknown. We hypothesized that Brussels chicory could enhance exhaustive aerobic exercise performance and post-exercise recovery by promoting lactate oxidation. Methods: This is a [...] Read more.
Background: Brussels chicory affluent in phenolic acids could inhibit atherosclerosis; however, its effects on exercise performance and post-exercise recovery are unknown. We hypothesized that Brussels chicory could enhance exhaustive aerobic exercise performance and post-exercise recovery by promoting lactate oxidation. Methods: This is a single-blind, randomized, placebo-controlled two-way cross-over trial involving 32 untrained college students (men 18) who consumed either Brussels chicory juice (100 g of Brussels chicory containing ~130 mg phenolic acids and 180 mL fresh milk) or placebo (180 mL fresh milk) for 7 days with a 2-week washout period. On the 7th day, participants received a short-term, progressive workload, high-intensity, exhaustive aerobic exercise with the Bruce protocol. Time to exhaustion and blood lactate were evaluated after exercise. C2C12 myotubes were treated with Brussels chicory phenolic acids (0.625–10 μM) to evaluate these effects on lactate metabolism and lactate dehydrogenase A (LDHA) and B (LDHB), two enzymes responsible for lactate biosynthesis and oxidation, respectively. Results: Brussels chicory consumption increased time to exhaustion by 8.3% and 12.2% for men and women participants, respectively. This administration also promoted post-exercise recovery, evidenced by a reduction in blood lactate (14.5% for men and 10.6% for women). In C2C12 myotubes, Brussels chicory protocatechuic acid and caffeic acid did not affect LHDA-mediated lactate production, whereas these compounds dose-dependently promoted LDHB-mediated lactate oxidation through an enrichment of mitochondria LDHB. Conclusions: Dietary supplementation with Brussels chicory may enhance short-term, progressive workload, high-intensity, exhaustive aerobic exercise performance and post-exercise recovery in humans, possibly by accelerating LDHB-mediated lactate oxidation. Full article
(This article belongs to the Special Issue Sports Nutrition: Current and Novel Insights—2nd Edition)
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<p>CONSORT (Consolidated Standards of Reporting Trials) flow diagram indicating the design of the trial.</p>
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<p>Effect of Brussels chicory on exercise performance. Content of the free phenolic acids in Brussels chicory (<span class="html-italic">n</span> = 3) (<b>A</b>), serum concentrations of protocatechuic acid and caffeic acid 0 min after exhaustive aerobic exercise (<b>B</b>), effect of dietary supplementation with Brussels chicory on time to exhaustion (<b>C</b>) and VO<sub>2</sub>max (<b>D</b>) in exhaustive aerobic exercise, blood bicarbonate (<b>E</b>) and pH (<b>F</b>) levels 0 min after exhaustive aerobic exercise. Data are mean ± SD. (<b>B</b>–<b>F</b>), <span class="html-italic">n</span> = 32. One-way repeated measures ANOVA, * <span class="html-italic">p</span> &lt; 0.05, significantly different from placebo. Abbreviation: VO<sub>2</sub>max, maximal oxygen consumption; PCA, protocatechuic acid; GA, gallic acid; PHBA, p-hydroxybenzoic acid; CRA, chlorogenic acid; CTA, caftaric acid; CFA, caffeic acid; ANOVA, analysis of variance.</p>
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<p>Effect of Brussels chicory on post-exercise recovery. The concentrations and areas under the curve (AUC) of blood lactate (<b>A</b>), blood glucose (<b>B</b>), heart rate (<b>C</b>), SBP (<b>D</b>), and DBP (<b>E</b>) 0, 5, 15, and 60 min after exhaustive aerobic exercise. Data are mean ± SD (<span class="html-italic">n</span> = 32). <span class="html-italic">p</span> &lt; 0.05 when compared by two-way repeated measures ANOVA followed by the Bonferroni correction for post-hoc comparisons. Differences in AUC between the Brussels chicory and the placebo groups were analyzed using a one-way repeated measures ANOVA. * <span class="html-italic">p</span> &lt; 0.05, significantly different from placebo in men. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, significantly different from placebo in women, NS, nonsignificant. Abbreviation: AUC, area under the curve; SBP, systolic blood pressure; DBP, diastolic blood pressure; ANOVA, analysis of variance.</p>
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<p>Effect of Brussels chicory phenolic acids on the levels of intracellular and conditioned medium lactate in myotubes. C2C12 myotubes were exposed to 10 μM of seven Brussels chicory phenolic acids, including PCA, GA, PHBA, CRA, CTA, and CFA, either individually or as a mix, for 24 h. After a 6 h incubation with 20 mM lactate, intracellular and conditioned medium lactate concentrations were measured (<b>A</b>,<b>B</b>). To further explore the effects, C2C12 myotubes were treated with PCA and CFA at multiple concentrations, as well as with a 10 μM mix for 24 h (<b>C</b>,<b>D</b>) or were exposed to a 10 μM of PCA and CFA at different time intervals (<b>E</b>,<b>F</b>). Data are mean ± SEM (<span class="html-italic">n</span> = 6), Student’s <span class="html-italic">t</span> test. (<b>A</b>–<b>D</b>), * <span class="html-italic">p</span> &lt; 0.05 vs. control. (<b>E</b>,<b>F</b>), * <span class="html-italic">p</span> &lt; 0.05 vs. control at 12, 24, and 36 h, respectively. NS, nonsignificant. Abbreviation: PCA, protocatechuic acid; GA, gallic acid; PHBA, p-hydroxybenzoic acid; CRA, chlorogenic acid; CTA, caftaric acid; CFA, caffeic acid; Mix, containing equal molar concentrations of all tested Brussels chicory phenolic acids.</p>
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<p>Brussels chicory’s phenolic acids promote lactate oxidation via targeting LDHB in myotubes. C2C12 myotubes were pre-treated with 10 μM PCA, CFA, or a mix for 24 h, then incubated with lactate for another 6 h in the presence or absence of AXKO-0046 (an inhibitor of lactate oxidation) or oxamate (an inhibitor of lactate production). Intracellular and conditioned medium lactate levels were measured in C2C12 myotubes treated with AXKO-0046 (<b>A</b>,<b>B</b>) and oxamate (<b>C</b>,<b>D</b>). C2C12 myotubes with LDHB knockdown were treated with PCA, CFA, or the mix for 24 h, followed by a 6 h incubation with lactate. Intracellular and conditioned medium lactate levels were then measured (<b>E</b>,<b>F</b>). C2C12 myotubes pre-treated with PCA, CFA, and the mix were incubated with [<sup>14</sup>C] lactate for 6 h to measure oxidation to CO<sub>2</sub>, which was trapped and quantified by liquid scintillation (<b>G</b>). Mitochondrial function was assessed using the Seahorse XFe96 analyzer, measuring OCR (<b>H</b>) and ECAR (<b>I</b>). Data are mean ± SEM (<span class="html-italic">n</span> = 6), Student’s <span class="html-italic">t</span> test, * <span class="html-italic">p</span> &lt; 0.05 vs. control for PCA, CFA, or the mix. (<b>H</b>,<b>I</b>) Data are mean ± SEM (<span class="html-italic">n</span> = 6), two-way repeated measure ANOVA. NS, nonsignificant. Abbreviation: LDHB, lactate dehydrogenase B; PCA, protocatechuic acid; CFA, caffeic acid; Mix, containing equal molar concentrations of all six Brussels chicory phenolic acids; OCR, oxygen consumption rate; ECAR, extracellular acidification rate.</p>
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<p>Mitochondria LDHB mediates the effect of Brussels chicory’s phenolic acids on lactate oxidation in the myotubes. qRT-PCR (<b>A</b>) and western blot (<b>B</b>,<b>C</b>) analyses were conducted to assess the key enzymes involved in lactate oxidation and production in C2C12 myotubes treated with PCA, CFA, or a mix for 24 h. The distribution of LDHB between mitochondria and the cytosol was examined in C2C12 myotubes (<b>D</b>). The activities of LDHB in mitochondria was measured (<b>E</b>). C2C12 myotubes with CD147 knockdown were treated with PCA, CFA, or a mix for 24 h, followed by an additional 6 h incubation with lactate. The levels of intracellular and conditioned medium lactate were then measured (<b>F</b>,<b>G</b>). Data are mean ± SEM (<span class="html-italic">n</span> = 6), Students’ <span class="html-italic">t</span> test. D and G, * <span class="html-italic">p</span> &lt; 0.05 vs. control. NS, nonsignificant. Abbreviation: LDHB, lactate dehydrogenase B; PCA, protocatechuic acid; CFA, caffeic acid; Mix, containing equal molar concentration of all six Brussels chicory’s phenolic acids; CD147, cluster of differentiation 147; Cyto, cytosol; Mito, mitochondria.</p>
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21 pages, 667 KiB  
Article
The Impact of the Digital Economy on Urban Ecosystem Resilience in the Yellow River Basin
by Yu Wang and Yupu Li
Sustainability 2025, 17(2), 790; https://doi.org/10.3390/su17020790 (registering DOI) - 20 Jan 2025
Abstract
The digital economy is key to ecological security in the Yellow River Basin and to harmonious coexistence between humans and nature. This study uses data from 80 cities in the Yellow River Basin from 2010 to 2022 to examine how the digital economy [...] Read more.
The digital economy is key to ecological security in the Yellow River Basin and to harmonious coexistence between humans and nature. This study uses data from 80 cities in the Yellow River Basin from 2010 to 2022 to examine how the digital economy affects urban ecological resilience. It uses three models to do this. The conclusion that the development of digital economy in the Yellow River Basin can significantly promote the enhancement of urban ecological environment resilience still holds after the robustness tests of phased regression, variable substitution and the introduction of instrumental variables. There is regional heterogeneity in the impact of digital economy on urban ecosystem resilience, showing the unbalanced spatial characteristics that the middle reaches are the highest, the upper reaches are the second highest, and the lower reaches are the lowest. The digital economy was shown to influence ecological resilience through a “double fixed-effects model” and a mediation effect model, via two intermediary pathways: “digital economy development → industrial structure upgrading → ecological resilience enhancement” and “digital economy development → resource allocation improvement → ecological resilience enhancement”. The digital economy was shown to transform and upgrade industrial structures and optimize capital and labor allocation, strengthening the ecological resilience of cities in the Yellow River Basin. Full article
(This article belongs to the Special Issue Ecology, Environment, and Watershed Management)
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<p>Mechanism of action of digital economy affecting urban ecosystem resilience in the Yellow River Basin.</p>
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27 pages, 1240 KiB  
Article
Impact of Ethical Leadership on Autonomy and Self-Efficacy in Virtual Work Environments: The Disintegrating Effect of an Egoistic Climate
by Carlos Santiago-Torner, José-Antonio Corral-Marfil, Yirsa Jiménez-Pérez and Elisenda Tarrats-Pons
Behav. Sci. 2025, 15(1), 95; https://doi.org/10.3390/bs15010095 (registering DOI) - 20 Jan 2025
Viewed by 73
Abstract
Ethical management is key to ensuring organizational sustainability, through resources such as autonomy or self-efficacy. However, economic and social uncertainty occasionally leads to adaptive responses that prioritize profit as the primary interest, blurring the integrating role of ethical leadership. There are a number [...] Read more.
Ethical management is key to ensuring organizational sustainability, through resources such as autonomy or self-efficacy. However, economic and social uncertainty occasionally leads to adaptive responses that prioritize profit as the primary interest, blurring the integrating role of ethical leadership. There are a number of studies that support this reality in a virtual work environment. This sector-specific and cross-sectional research explores how ethical leadership influences self-efficacy among teleworkers, through active commitment to job autonomy, and how an egoistic climate hinders this influence. The analysis is quantitative and correlational, and the sample includes 448 teleworkers. A model of conditional indirect effects, including both a mediation process and a moderation process, is used. The results support that ethical leadership enhances followers’ self-efficacy through a redistribution of responsibilities, which increases the perception of autonomy. However, when ethical leadership coincides with a climate that has opposing interests, such as an egoistic climate, ethical leadership is unable to counteract it, and its effect on self-efficacy gradually diminishes. The benefits of this management style are widely known, but it is crucial to understand under what circumstances it loses efficacy. This research presents a new theoretical model that contributes to the existing literature on ethical leadership. Lastly, organizations that embrace ethical leadership can avoid the emergence of ethical climates disconnected from collective benefit, such as those characterized by selfishness, which hinder prosocial motivation. In this context, ethical leadership fosters the development of high-quality interpersonal relationships with followers, which are considered essential for creating an environment conducive to group learning. Consequently, change management in organizations necessitates the adoption of an ethical system that enhances self-efficacy through moral principles, rather than relying solely on individualistic aspects. Full article
(This article belongs to the Special Issue Leadership in the New Era of Technology)
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<p>Research model.</p>
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<p>Includes the value of the regression coefficients calculated for each of the variables studied. Regression analysis. Non-standardized coefficients. * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Moderation of the egoistic ethical climate (low, medium, and high perception) on the relationship between ethical leadership and self-efficacy. The greater the perception of an egoistic ethical climate, the lesser the influence of ethical leadership on follower self-efficacy.</p>
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<p>Conditional effect of ethical leadership on job self-efficacy, depending on the different values of the moderating variable (egoistic ethical climate).</p>
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12 pages, 2479 KiB  
Article
VsMATE1-Mediated Citrate Efflux Is Involved in Al Resistance in Common Vetch (Vicia sativa L.)
by Wenhui Yan, Jia Shi, Ling He, Zigang Hou, Zhenfei Guo and Haifeng Zhu
Plants 2025, 14(2), 290; https://doi.org/10.3390/plants14020290 - 20 Jan 2025
Viewed by 71
Abstract
Planting aluminum-tolerant legume green manure is a cost-effective and sustainable method to increase soil fertility as well as decrease Al toxicity in acidic soils. By analyzing the relative root elongation of seven legume green manure species, common vetch (Vicia sativa L.) was [...] Read more.
Planting aluminum-tolerant legume green manure is a cost-effective and sustainable method to increase soil fertility as well as decrease Al toxicity in acidic soils. By analyzing the relative root elongation of seven legume green manure species, common vetch (Vicia sativa L.) was identified as an Al-resistant species. Furthermore, cultivars 418 (cv. Sujian No.3) and 426 (cv. Lanjian No.3) were identified as Al-resistant and -sensitive cultivars, respectively, among 12 common vetch germplasms. The root growth of 418 was less inhibited by Al toxicity in both the germination stage and seedling stage than that of 426. Under Al toxicity, 418 accumulated less Al in both roots and shoots. Citrate is more abundant in the roots of common vetch compared to oxalate or malate. The internal citrate contents showed no significant difference between 418 and 426 under either control or Al treatment. However, the citrate efflux increased in response to Al in 418 but not in 426 and was higher in 418 under Al stress than in 426. Consistently, VsMATE1 expression increased faster and to a greater extent in 418 than 426 in response to Al stress. These results indicated that a VsMATE1-mediated citrate efflux might play an important role in Al resistance in common vetch. It is suggested that VsMATE1 is a valuable candidate gene for aluminum resistance breeding. Full article
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<p>Correlation between relative root elongation and Al concentration in <span class="html-italic">Vicia villosa</span> (<b>a</b>), <span class="html-italic">Vica sativa</span> (<b>b</b>), <span class="html-italic">Melitotus albus</span> (<b>c</b>), <span class="html-italic">Trifolium pretense</span> (<b>d</b>), <span class="html-italic">Trifolium repens</span> (<b>e</b>), <span class="html-italic">Medicago sativa</span> (<b>f</b>), and <span class="html-italic">Astragalus sinicus</span> (<b>g</b>). Seedlings were treated with a 0.5 mM CaCl<sub>2</sub> solution (pH 4.5) containing different concentrations of AlCl<sub>3</sub> for 24 h. Root length was measured, and the relative root elongation was calculated. The correlation between Al concentration and relative root elongation was obtained via linear regression analysis, and semi-inhibitory concentrations were calculated.</p>
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<p>Analysis of Al tolerance in common vetch collections. The germinated seeds were treated with 0.5 mM CaCl<sub>2</sub> solution (pH 4.5) containing 0 or 25 µM AlCl<sub>3</sub> for 24 h. Root length was measured, and the relative root elongation was calculated. Data are means ± SD (n = 10). Columns with different letters indicate significant differences at <span class="html-italic">p</span> &lt; 0.05 (one-way ANOVA followed by Tukey’s post hoc test).</p>
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<p>Effect of Al toxicity on relative root elongation and Al accumulation in roots of Al-resistant cultivar (418) and Al-sensitive cultivar (426) at germination stage. Five-day-old seedlings were treated with 0.5 mM CaCl<sub>2</sub> solution (pH 4.5) containing 0, 5, 10, or 15 µM AlCl<sub>3</sub> for 24 h. (<b>a</b>) Root length was measured, and the relative root elongation was calculated. Data are means ± SD (n = 10). n.s. and * represent no and significant differences at <span class="html-italic">p</span> &lt; 0.05 (two-way ANOVA followed by Tukey’s post hoc test; multiple comparisons were made between 418 and 426). (<b>b</b>) Roots were stained by hematoxylin and photographed. Bar = 1 mm. (<b>c</b>) Aluminum in root surface was extracted by soaking roots (0–2 cm) in 1 N nitric acid for more than 2 days, and Al content was analyzed by ICP-OES. Data are means ± SD (n = 3). n.s. and * represent no and significant differences at <span class="html-italic">p</span> &lt; 0.05 (two-way ANOVA followed by Tukey’s post hoc test; multiple comparison was made between 418 and 426).</p>
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<p>Effect of aluminum on root elongation and Al content in root of Al-tolerant cultivar (418) and Al-sensitive cultivar (426) in seedling stage. Two-week-old seedlings were treated with 1/2 Hoagland solution (pH 5.0) containing 0, 500, or 750 µM AlCl<sub>3</sub> for 12 days. (<b>a</b>) Root length was measured, and the relative root elongation was calculated. Data are means ± SD (n = 15). (<b>b</b>,<b>c</b>) Al content in roots and shoots were analyzed. Data are means ± SD (n = 3). n.s. and * represents no and significant differences at <span class="html-italic">p</span> &lt; 0.05 (two-way ANOVA followed by Tukey’s post hoc test; multiple comparisons were made between 418 and 426).</p>
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<p>Effect of aluminum on internal root organic acid and secreted citrate content on Al-resistant cultivar (418) and Al-sensitive cultivar (426). Two-week-old seedlings were treated with 0.5 mM CaCl<sub>2</sub> solution (pH 4.5) containing 0 or 15 µM AlCl<sub>3</sub> for 24 h. (<b>a</b>) Oxalate, (<b>b</b>) malate, and (<b>c</b>) citrate contents in roots; (<b>d</b>) secreted oxalate; and (<b>e</b>) citrate content in cultivation solution were measured using HPLC. Data are means ± SD (n = 4). Columns with different letters indicate significant differences at <span class="html-italic">p</span> &lt; 0.05 (two-way ANOVA followed by Tukey’s post hoc test; multiple comparisons were made between columns).</p>
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<p>Citrate efflux from roots of Al-resistant cultivar (418) and Al-sensitive cultivar (426) in response to Al toxicity. Five-day-old seedlings were treated with 0.5 mM CaCl<sub>2</sub> solution (pH 4.5) containing 0 or 15 µM AlCl<sub>3</sub> for 12 h. Secreted citrate contents in cultivation solution were measured with an enzyme assay as described previously [<a href="#B25-plants-14-00290" class="html-bibr">25</a>]. Data are means ± SD (n = 4). Columns with different letters indicate significant differences at <span class="html-italic">p</span> &lt; 0.05 (two-way ANOVA followed by Tukey’s post hoc test; multiple comparisons were made between columns).</p>
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<p>Relative expression of VsMATE1 in Al-resistant cultivar (418) and Al-sensitive cultivar (426). Five-day-old seedlings were treated with 0.5 mM CaCl<sub>2</sub> solution (pH 4.5) containing 0 or 15 µM AlCl<sub>3</sub> for 24 h. (<b>a</b>) Relative expression of <span class="html-italic">VsMATE1</span> in roots was analyzed by qRT-PCR. (<b>b</b>) The relative expression level under Al stress was divided by the relative expression level in the control group to get the fold change of <span class="html-italic">VsMATE1</span> expression. Data are means ± SD (n = 3). Columns with different letters indicate significant difference at <span class="html-italic">p</span> &lt; 0.05 (two-way ANOVA followed by Tukey’s post hoc test; multiple comparisons were made between columns). n.s. and * represents no and significant differences at <span class="html-italic">p</span> &lt; 0.05 (two-way ANOVA followed by Tukey’s post hoc test; multiple comparisons were made between 418 and 426).</p>
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20 pages, 4662 KiB  
Article
Metabolics-Based Study on the Therapeutic Mechanism Behind the Effect of Shenhuang Plaster Applied to the Shenque Acupoint on Gastrointestinal Motility in POI Mice
by Yanan Shi, Chenglei Wu, Ting Liu, Rongyun Wang, Bin Ding and Qiuhua Sun
Metabolites 2025, 15(1), 65; https://doi.org/10.3390/metabo15010065 - 20 Jan 2025
Viewed by 137
Abstract
Background: Postoperative ileus (POI) is a common postoperative clinical complication that significantly affects postoperative rehabilitation and quality of life in patients and can even produce secondary complications, leading to serious consequences. External treatment using Shenhuang Plaster (SHP) (Shenque acupoint administration) has definite effects [...] Read more.
Background: Postoperative ileus (POI) is a common postoperative clinical complication that significantly affects postoperative rehabilitation and quality of life in patients and can even produce secondary complications, leading to serious consequences. External treatment using Shenhuang Plaster (SHP) (Shenque acupoint administration) has definite effects and unique advantages in the prevention and treatment of POI, but its mechanism is not completely clear. In this study, we investigated the therapeutic mechanism behind the effect of Shenhuang Plaster applied to the Shenque acupoint on gastrointestinal motility in POI mice based on metabolomics. Materials and Methods: C57BL/6 mice were divided into three groups: blank control (Ctrl), model (POI), and intervention (POI + SHP) groups. SHP treatment was started 3 days before modeling. We employed several behavioral tests and gastrointestinal transit function measurements and performed qRT-PCR analysis, 16S rRNA gene sequencing, and metabolomics analysis on serum metabolites. Results: We found that SHP could reduce the mRNA expression of inflammatory mediators in the smooth muscle tissue of the small intestine, regulate the structure and function of the intestinal microbiota, and modulate serum phenylalanine, carnitine, and glutamic acid levels. Conclusions: POI mice had obvious intestinal flora disorders and metabolic disorders of amino acids and their derivatives, and there was a significant correlation between differential flora and differential metabolites. SHP could effectively regulate the concentration of intestinal flora and serum metabolites and the metabolic pathway related to amino acids in vivo and, ultimately, achieve a therapeutic purpose in POI. In this study, it was found, for the first time, that applying SHP to the Shenque acupoint could effectively regulate the serum metabolites of phenylalanine, carnitine, and glutamate, and improve postoperative intestinal motile disturbance through association with the intestinal flora. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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<p>Gastrointestinal transport curves in each group of mice. Note: Gastrointestinal transport curves showing fluorescently labeled dextran in the gastrointestinal tract (St, stomach; SI, small intestine segments 1–10; Co, colon segments 1–4).</p>
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<p>Relative mRNA expression of inflammatory factors in small-intestinal smooth muscle of mice in each group. Note: POI vs. Ctrl, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001; <sup>△</sup> POI + SHP vs. POI, <sup>△</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>△△</sup> <span class="html-italic">p</span> &lt; 0.01, <sup>△△△</sup> <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Comparison of the alpha diversity of gut microbiota in each group—Simpson. Note: POI vs. Ctrl, ** <span class="html-italic">p</span> &lt; 0.01; POI + SHP vs. POI, ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>PCoA of gut microbiota in each group of mice.</p>
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<p>NMDS analysis of gut microbiota in each group of mice.</p>
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<p>Heatmap of significantly altered metabolites among different groups of mice.</p>
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<p>PLS-DA analysis of serum metabolites in each group of mice.</p>
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<p>OPLS-DA analysis of serum metabolites in each group of mice.</p>
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<p>Enrichment pathways of differential metabolites among the three groups of mice.</p>
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<p>Correlation analysis between differential metabolites and differential gut microbiota. Note: POI vs. Ctrl, POI + SHP vs. POI, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01.</p>
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19 pages, 857 KiB  
Article
The Transformative Power of Embodied Behaviour: Influencing Tourists’ Experience in the Guangzhou Marathon as a Mass Participant Sports Event
by Xin Xu and Guangquan Dai
Behav. Sci. 2025, 15(1), 90; https://doi.org/10.3390/bs15010090 (registering DOI) - 20 Jan 2025
Viewed by 212
Abstract
Mass-participation sports events (MPSEs) are of significant value to the fields of sports, culture, and tourism. MPSEs have witnessed a remarkable surge in popularity, which has led to a complex interplay of factors influencing participants’ overall experience, making it crucial to understand the [...] Read more.
Mass-participation sports events (MPSEs) are of significant value to the fields of sports, culture, and tourism. MPSEs have witnessed a remarkable surge in popularity, which has led to a complex interplay of factors influencing participants’ overall experience, making it crucial to understand the role of embodied behaviour. However, the existing literature is deficient in terms of providing substantial evidence, particularly with regard to the growing significance of experience planning as a core aspect of event design. This research employed the Guangzhou Marathon, one of the most renowned MPSEs in China, as a case study. The objective of this research is to investigate and extend the knowledge of the embodied behaviour of MPSE tourists through the mixed method of a questionnaire survey together with interviews. Furthermore, this research aimed to explore the antecedents and consequences of the embodied experience formation process. The findings demonstrated the pivotal role of the embodied experience in shaping tourist perceptions and subsequent intentions. Specifically, this research suggested that tourist behaviour with experience and attachment influenced the perceived value and cost of participation willingness through moderating and mediating effects. The findings contribute to the existing knowledge on sports tourism and behavioural studies and provide sustainable event management strategies. Full article
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<p>Theoretical framework.</p>
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<p>Moderated effect of event attachment. (<b>a</b>) Moderating role of event attachment in the relationship between perceived value and embodied experience. (<b>b</b>) Moderating role of event attachment in the relationship between perceived cost and embodied experience.</p>
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14 pages, 1295 KiB  
Article
Resilience of Spontaneously Hypertensive Rats to Secondary Insults After Traumatic Brain Injury: Immediate Seizures, Survival, and Stress Response
by Ilia Komoltsev, Olga Kostyunina, Pavel Kostrukov, Daria Bashkatova, Daria Shalneva, Stepan Frankevich, Olga Salyp, Natalia Shirobokova, Aleksandra Volkova, Aleksandra Soloveva, Margarita Novikova and Natalia Gulyaeva
Int. J. Mol. Sci. 2025, 26(2), 829; https://doi.org/10.3390/ijms26020829 (registering DOI) - 19 Jan 2025
Viewed by 538
Abstract
Traumatic brain injury (TBI) is one of the primary causes of mortality and disability, with arterial blood pressure being an important factor in the clinical management of TBI. Spontaneously hypertensive rats (SHRs), widely used as a model of essential hypertension and vascular dementia, [...] Read more.
Traumatic brain injury (TBI) is one of the primary causes of mortality and disability, with arterial blood pressure being an important factor in the clinical management of TBI. Spontaneously hypertensive rats (SHRs), widely used as a model of essential hypertension and vascular dementia, demonstrate dysfunction of the hypothalamic–pituitary–adrenal axis, which may contribute to glucocorticoid-mediated hippocampal damage. The aim of this study was to assess acute post-TBI seizures, delayed mortality, and hippocampal pathology in SHRs and normotensive Sprague Dawley rats (SDRs). Male adult SDRs and SHRs were subjected to lateral fluid-percussion injury. Immediate seizures were video recorded, corticosterone (CS) was measured in blood plasma throughout the study, and hippocampal morphology assessed 3 months post-TBI. Acute and remote survival rates were significantly higher in the SHRs compared to the SDRs (overall mortality 0% and 58%, respectively). Immediate seizure duration predicted acute but not remote mortality. TBI did not affect blood CS in the SHRs, while the CS level was transiently elevated in the SDRs, predicting remote mortality. Neuronal cell loss in the polymorph layer of ipsilateral dentate gyrus was found in both the SDRs and SHRs, while thinning of hippocampal pyramidal and granular cell layers were strain- and area-specific. No remote effects of TBI on the density of astrocytes or microglia were revealed. SHRs possess a unique resilience to TBI as compared with normotensive SDRs. SHRs show shorter immediate seizures and reduced CS response to the injury, suggesting the development of long-term adaptative mechanisms associated with chronic hypertension. Though remote post-traumatic hippocampal damage in ipsilateral dentate gyrus is obvious in both SHRs and SDRs, the data imply that physiological adaptations to high blood pressure in SHRs may be protective, preventing TBI-induced mortality but not hippocampal neurodegeneration. Understanding the mechanisms of resilience to TBI may also help improve clinical recommendations for patients with hypertension. Limitation: since more than a half of the SDRs with prolonged immediate seizures or elevated CS 3 days after TBI have died, survivorship bias might hamper correct interpretation of the data. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Epilepsy—3rd Edition)
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<p>Acute and remote mortality in SDRs and SHRs. (<b>A</b>) The proportion of acute and remote mortality in SDRs and SHRs; ###—<span class="html-italic">p</span> &lt; 0.001, χ<sup>2</sup> test. (<b>B</b>) Survival curves according to the Kaplan–Meier method; <span class="html-italic">p</span> = 0.001. SHRs: TBI group n = 15 and SDRs: TBI group n = 26.</p>
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<p>Immediate seizures in SHRs and SDRs and prediction of acute mortality. The durations of seizures (<b>A</b>), apnea (<b>B</b>), and recovery of pose (<b>C</b>) were shorter in SHRs, while rats with paw cyanosis (<b>D</b>) were absent in the SHR group. (<b>E</b>) The duration of seizures immediately after TBI was longer in the SDRs that died within 10 min after LFPI. (<b>F</b>) The duration of apnea and (<b>G</b>) recovery of pain sensitivity was longer in the SDRs that died. (<b>H</b>) ROC analysis: the duration of immediate seizures predicted acute mortality. For (<b>E</b>–<b>H</b>), mixed SDRs + SHRs group was used. (<b>A</b>–<b>G</b>)—the data are presented as M ± SEM. *—<span class="html-italic">p</span> &lt; 0.05; ***—<span class="html-italic">p</span> &lt; 0.001 (Mann–Whitney test); and ##—<span class="html-italic">p</span> &lt; 0.01 (χ<sup>2</sup> test). SHRs: TBI group n = 15 and SDRs: TBI group n = 26.</p>
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<p>Blood serum CS time course and late mortality prediction. (<b>A</b>) Changes in CS levels during the experiment in sham-operated and TBI groups of SDRs and SHRs. An increase in CS was revealed on day 3 after TBI in SDRs. (<b>B</b>) Three months after TBI or sham operation, a short forced-swim-test-induced increase in blood plasma CS in sham-operated and TBI groups of SHRs and SDRs qq. (<b>C</b>) ROC analysis: CS level on day 3 predicted late mortality. (<b>D</b>) ROC analysis: immediate seizure duration did not predict late mortality. (<b>A</b>,<b>B</b>)—the data are presented as M ± SEM. ***—<span class="html-italic">p</span> &lt; 0.005; Mann–Whitney test; #—<span class="html-italic">p</span> &lt; 0.05; and RM ANOVA for time factor. For (<b>C</b>,<b>D</b>), mixed SDRs + SHRs group was used. SHRs: TBI group n = 15 and sham group n = 10 and SDRs: TBI group n = 26 and sham group n = 16.</p>
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<p>Neuronal and glial cell density in the hippocampus 3 months after TBI or sham operation. (<b>A</b>,<b>B</b>) Neuronal cell density in the DG of SDRs and SHRs, respectively. Neuronal cell density was lower in the polymorph layer of the ipsilateral hippocampus in both rat strains. (<b>C</b>) Representative microphotograph with neurodegeneration in the ipsilateral DG (polymorph layer is marked by the arrow), Nissl staining. (<b>D</b>,<b>E</b>) Astroglal cell density in the hippocampi of SDRs and SHRs, respectively. (<b>F</b>) Representative microphotograph (SHRs, ipsilateral DG), GFAP staining. (<b>G</b>,<b>H</b>) Microglial cell density in the hippocampi of SDRs and SHRs, respectively. Microglial activation was detected only in the contralateral DG of SDRs. (<b>I</b>) Representative microphotograph (SHR, ipsilateral DG), Iba1 staining. (<b>A</b>,<b>B</b>,<b>D</b>,<b>E</b>,<b>G</b>,<b>H</b>)—the data are presented as M ± SEM. *—<span class="html-italic">p</span> &lt; 0.05, Mann–Whitney test. SHRs: TBI group n = 15 and sham group n = 10 and SDRs: TBI group n = 26 and sham group n = 16.</p>
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18 pages, 5437 KiB  
Article
Navigating the Collective: Nanoparticle-Assisted Identification of Leader Cancer Cells During Migration
by Anastasia Alexandrova, Elizaveta Kontareva, Margarita Pustovalova, Sergey Leonov and Yulia Merkher
Life 2025, 15(1), 127; https://doi.org/10.3390/life15010127 - 19 Jan 2025
Viewed by 448
Abstract
Cancer-related deaths primarily occur due to metastasis, a process involving the migration and invasion of cancer cells. In most solid tumors, metastasis occurs through collective cell migration (CCM), guided by “cellular leaders”. These leader cells generate forces through actomyosin-mediated protrusion and contractility. The [...] Read more.
Cancer-related deaths primarily occur due to metastasis, a process involving the migration and invasion of cancer cells. In most solid tumors, metastasis occurs through collective cell migration (CCM), guided by “cellular leaders”. These leader cells generate forces through actomyosin-mediated protrusion and contractility. The cytoskeletal mechanisms employed by metastatic cells during the migration process closely resemble the use of the actin cytoskeleton in endocytosis. In our previous work, we revealed that tumor cells exhibiting high metastatic potential (MP) are more adept at encapsulating 100–200 nm nanoparticles than those with lower MP. The objective of this study was to investigate whether nanoparticle encapsulation could effectively differentiate leader tumor cells during their CCM. To achieve our objectives, we employed a two-dimensional CCM model grounded in the wound-healing (“scratch”) assay, utilizing two breast cancer cell lines, MCF7 and MDA-MB-231, which display low and high migratory potential, respectively. We conducted calibration experiments to identify the “optimal time” at which cells exhibit peak speed during wound closure. Furthermore, we carried out experiments to assess nanoparticle uptake, calculating the colocalization coefficient, and employed phalloidin staining to analyze the anisotropy and orientation of actin filaments. The highest activity for low-MP cells was achieved at 2.6 h during the calibration experiments, whereas high-MP cells were maximally active at 3.9 h, resulting in 8% and 11% reductions in wound area, respectively. We observed a significant difference in encapsulation efficiency between leader and peripheral cells for both high-MP (p < 0.013) and low-MP (p < 0.02) cells. Moreover, leader cells demonstrated a considerably higher anisotropy coefficient (p < 0.029), indicating a more organized, directional structure of actin filaments compared to peripheral cells. Thus, nanoparticle encapsulation offers a groundbreaking approach to identifying the most aggressive and invasive leader cells during the CCM process in breast cancer. Detecting these cells is crucial for developing targeted therapies that can effectively curb metastasis and improve patient outcomes. Full article
(This article belongs to the Special Issue Advancing Nanotechnology in Cancer Theranostics)
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<p>Graphical representation of calibration experiments of the in vitro wound-healing assay. This technique involves basic steps applicable to almost all cell types: (1) cell seeding and preparation; (2) making a linear thin scratch (creating a gap or “wound”) in a confluent cell monolayer; (3) acquiring data through microscopic imaging and measuring wound healing (gap closure) at each time point; and (4) data analysis.</p>
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<p>Graphical representation of workflow of nanoparticle encapsulation and actin staining during the in vitro wound-healing assay. This technique involves basic steps applicable to a wound-healing assay. For encapsulation experiments, 200 nm nanoparticles were added one hour before the OT. For experiments with actin markers, Phalloidin-iFluor 488 was added for 90 min following fixation of cells at OT.</p>
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<p>Schematic representation of the calculation of actin filament anisotropy and orientation. The diagram shows the structure of the cytoskeleton. Maroon indicates microtubules, while actin filaments are indicated in purple and blue. Black parallel lines show the way anisotropy is calculated. A coordinate system has been introduced. θ is the filament angle with respect to x. The orientation is determined by the angle—θ.</p>
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<p>Images from a scratch assay experiment at different time points within 11 h. (<b>A</b>) MDA-MB-231. (<b>B</b>) MCF7. Cells were plated on plastic dishes, wounded with a pipette tip, and then imaged over 12 h using a microscope equipped with a point-visiting function and live-cell apparatus. Scale bar = 100 µm. (<b>C</b>,<b>D</b>) The dependence of the closure coefficient (in percentage) on time (in hours) for MDA-MB-231 and MCF7cell lines, respectively. Error bars are standard deviations.</p>
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<p>Internalization of carboxylate-modified 200 nm nanoparticles by BC cells. (<b>A</b>,<b>B</b>) High-MP cells on the leading edge and periphery, respectively. (<b>C</b>,<b>D</b>) Low-MP cells on the leading edge and periphery, respectively. Scale bar = 100 µm. The inserts in panels A-D display a chosen region of interest (ROI) magnified five times. The red arrows indicate the nanoparticles. Scale bar = 7 µm. (<b>E</b>) Colocalization of 200 nm nanoparticles with BC cells represented as the average value of Pearson coefficient in the edge and on the periphery of wound. The light- and dark-pink colors indicate leader and peripheral MDA-MB-231 cells, respectively; light blue—leader; dark blue—peripheral MCF7 cells. Statistically significant parameters: ** <span class="html-italic">p</span> &lt; 0.013; * <span class="html-italic">p</span> &lt; 0.02. Error bars are standard errors.</p>
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<p>A typical image (selected FOVs × 40 magnification) of the phalloidin-stained actin fibers of LM (<b>A</b>,<b>C</b>) MCF7 and HM (<b>B</b>,<b>D</b>) MDA-MB-231 cells during migration. (<b>A</b>,<b>B</b>) Leader cells. (<b>C</b>,<b>D</b>) Peripheral cells. The inserts display a carefully chosen region of interest (ROI) magnified five times and taken while ensuring that no pixels became saturated. Output from FibrilTool: a line segment (red) is drawn, the angle of which represents the average orientation of the array and the length of which is proportional to the array’s anisotropy. The scale bar is 20 µm.</p>
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<p>Anisotropy (<b>A</b>) and orientation (<b>B</b>) obtained for all tested cell types.; *—<span class="html-italic">p</span> &lt; 0.02. (<b>C</b>) Anisotropy normalized by the Pearson colocalization coefficient. *—<span class="html-italic">p</span> &lt; 3 × 10<sup>−10</sup>; **—<span class="html-italic">p</span> &lt; 0.003. The light- and dark-pink colors indicate data for leader and peripheral MDA-MB-231 cells, respectively; light blue and dark blue indicate data for leader and peripheral MCF7 cells, respectively. Error bars are standard errors.</p>
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21 pages, 1290 KiB  
Article
How Livelihood Capital Affects Farmers’ Green Production Behavior: Analysis of Mediating Effects Based on Farmers’ Cognition
by Jieyu Yang and Xiujuan Cui
Sustainability 2025, 17(2), 763; https://doi.org/10.3390/su17020763 - 19 Jan 2025
Viewed by 398
Abstract
In light of global climate change and sustainable agricultural growth, it is critical to look at producers’ green production methods. Enhancing the quality of agricultural goods and reducing agricultural pollution are the main goals of future agricultural growth, and this is accomplished by [...] Read more.
In light of global climate change and sustainable agricultural growth, it is critical to look at producers’ green production methods. Enhancing the quality of agricultural goods and reducing agricultural pollution are the main goals of future agricultural growth, and this is accomplished by farmers using green production methods. Regarding the research data of 364 vegetable farmers, this study uses structural equation modeling and a mediation effect model to empirically assess the effect of livelihood capital and farmers’ cognition on their green behavior. The results show that (1) natural capital, human capital, financial capital, and social capital in the livelihood capital of vegetable growers may significantly impact producers’ green production behavior. It is not immediately clear how physical capital affects the way green manufacturing practices work. (2) Natural capital and green production behavior are completely mediated by environmental and policy cognition, while human capital and green production behavior are partly mediated by environmental and policy cognition. Human and natural capital indirectly influence farmers’ sustainable production techniques via these activities. Financial and social capital directly influence farmers’ sustainable production methods, with no mediation effect seen. (3) Farmers’ green production behavior is more significantly influenced by their cognitive behavior than by their livelihood capital. Accordingly, it is recommended that environmental education and policy promotion be strengthened, that farmers’ livelihood capital be accumulated via a variety of channels, that farmers’ subsidies for green production be increased, and that farmers’ knowledge of green production be improved. The cognitive level of farmers should also be raised. In addition to providing theoretical justification for analyzing farmers’ green production practices within the framework of sustainable agricultural development, this study also acts as a guide for pertinent government agencies to help farmers choose more ecologically friendly farming methods. Full article
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<p>Theoretical framework of livelihood capital that influences the green production behavior of agricultural households.</p>
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<p>Mediating variable action path diagram.</p>
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<p>Modified structural equation model diagram. Note: → represents the causal relationship between latent variables, pointing from the dependent variable to the effect variable, and e1–e26 denote the residuals of the observed variables in the measurement model and the measurement error of the structural model.</p>
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27 pages, 1004 KiB  
Article
When I Receive Too Much Social Support: The Effect of Social Support Overload on Users’ Life Burnout and Discontinuance in Fitness Apps
by Ruihan Li, Shuang Wang and Tailai Wu
Healthcare 2025, 13(2), 191; https://doi.org/10.3390/healthcare13020191 - 19 Jan 2025
Viewed by 221
Abstract
Background/Objectives: As fitness apps increasingly incorporate social interaction features, users may find themselves overwhelmed by an excess of received support, struggling to effectively manage it. Highlighting a novel recipient-centric perspective, we aim to investigate the impact of social support overload on users’ life [...] Read more.
Background/Objectives: As fitness apps increasingly incorporate social interaction features, users may find themselves overwhelmed by an excess of received support, struggling to effectively manage it. Highlighting a novel recipient-centric perspective, we aim to investigate the impact of social support overload on users’ life burnout and discontinuance within fitness apps. Methods: Utilizing Social Support Theory and Basic Psychological Needs Theory, we develop a model to examine how emotional, network, and informational support overload affect life burnout and discontinuance through the frustration of basic psychological needs: autonomy, competence, and relatedness. A total of 443 fitness app users were included in our study, and we employed Structural Equation Modeling (SEM) to empirically test this model. Results: The results highlight the significant mediating role of the frustration of basic psychological needs between social support overload and life burnout/discontinuance. Network and informational support overload positively correlate with frustration of all needs, whereas emotional support overload shows a complex relationship. All need frustrations are linked to life burnout, but only autonomy and relatedness frustrations significantly lead to discontinuance. Additionally, gender and app use proficiency are significant control variables impacting discontinuance. Conclusions: This study adopts a novel recipient-centric perspective to explore social support overload, examining its effects on life burnout and discontinuance and offering practical implications for both users and app managers. Full article
(This article belongs to the Section Artificial Intelligence in Medicine)
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<p>The research model.</p>
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<p>Structural model results. Note: *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.01, * <span class="html-italic">p</span> &lt; 0.05. NS represents not significant.</p>
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23 pages, 2942 KiB  
Article
Bone Marrow Stromal Cells Generate a Pro-Healing Inflammasome When Cultured on Titanium–Aluminum–Vanadium Surfaces with Microscale/Nanoscale Structural Features
by David J. Cohen, Christine M. Van Duyn, Jingyao Deng, Musaddiq K. Lodi, Michelle B. Gallagher, James T. Sugar, Jeremy J. Rawlinson, Preetam Ghosh, Barbara D. Boyan and Zvi Schwartz
Biomimetics 2025, 10(1), 66; https://doi.org/10.3390/biomimetics10010066 - 19 Jan 2025
Viewed by 402
Abstract
The surface topography and chemistry of titanium–aluminum–vanadium (Ti6Al4V) implants play critical roles in the osteoblast differentiation of human bone marrow stromal cells (MSCs) and the creation of an osteogenic microenvironment. To assess the effects of a microscale/nanoscale (MN) topography, this study compared the [...] Read more.
The surface topography and chemistry of titanium–aluminum–vanadium (Ti6Al4V) implants play critical roles in the osteoblast differentiation of human bone marrow stromal cells (MSCs) and the creation of an osteogenic microenvironment. To assess the effects of a microscale/nanoscale (MN) topography, this study compared the effects of MN-modified, anodized, and smooth Ti6Al4V surfaces on MSC response, and for the first time, directly contrasted MN-induced osteoblast differentiation with culture on tissue culture polystyrene (TCPS) in osteogenic medium (OM). Surface characterization revealed distinct differences in microroughness, composition, and topography among the Ti6Al4V substrates. MSCs on MN surfaces exhibited enhanced osteoblastic differentiation, evidenced by increased expression of RUNX2, SP7, BGLAP, BMP2, and BMPR1A (fold increases: 3.2, 1.8, 1.4, 1.3, and 1.2). The MN surface also induced a pro-healing inflammasome with upregulation of anti-inflammatory mediators (170–200% increase) and downregulation of pro-inflammatory factors (40–82% reduction). Integrin expression shifted towards osteoblast-associated integrins on MN surfaces. RNA-seq analysis revealed distinct gene expression profiles between MSCs on MN surfaces and those in OM, with only 199 shared genes out of over 1000 differentially expressed genes. Pathway analysis showed that MN surfaces promoted bone formation, maturation, and remodeling through non-canonical Wnt signaling, while OM stimulated endochondral bone development and mineralization via canonical Wnt3a signaling. These findings highlight the importance of Ti6Al4V surface properties in directing MSC differentiation and indicate that MN-modified surfaces act via signaling pathways that differ from OM culture methods, more accurately mimicking peri-implant osteogenesis in vivo. Full article
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<p>Optical profilometry measurements of surface micro-roughness of smooth machined (SM), anodized (AN), and micro/nano-rough (MN) Ti6Al4V surfaces: average peak-to-valley distance (<b>A</b>), skewness (<b>B</b>), microroughness (<b>C</b>), and kurtosis (<b>D</b>). Data are means ± SEM and were evaluated using analysis of variance (ANOVA) with Tukey post hoc test. Statistical significance was established at <span class="html-italic">p</span>-values equal to or less than 0.05 (*** <span class="html-italic">p</span> &lt; 0.001; **** <span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>Implant surface characterization of smooth machined (SM), anodized (AN), and micro/nano-rough (MN) Ti6Al4V surfaces: (<b>A</b>) X-ray photoelectron spectroscopy (XPS) was used to determine elemental composition, shown as mean atomic percentage (%) of carbon (<b>C</b>), oxygen (O), titanium (Ti), aluminum (Al), and vanadium (V). (<b>B</b>) Surface wettability was quantified through sessile drop contact angle measurements performed on each surface. (<b>C</b>) Semi-quantitative energy-dispersive X-ray spectroscopy (EDX) analysis of surface elemental composition was obtained from ion-milled cross-sections of each surface, shown as mean atomic percentage (%) of titanium (Ti), aluminum (Al), and vanadium (V). (<b>D</b>) X-ray diffraction (XRD) profiles were used to determine distribution of α-Ti and β-Ti phases for each surface material, with circles depicting α-Ti, whereas triangles distinguish β-Ti phase based on elemental reference standards for EDX. Data are presented as mean + SEM and were evaluated using analysis of variance (ANOVA) with Tukey post hoc test. Statistical significance was established at <span class="html-italic">p</span>-values equal to or less than 0.05 (*** <span class="html-italic">p</span> &lt; 0.001; **** <span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>Characterization of surface topography using scanning electron microscopy (SEM). SEM micrographs/images of smooth, anodized, and micro/nano-rough (MN) Ti6Al4V surfaces were captured at macroscale (35×), microscale (1000×), mesoscale (10,000×), and nanoscale (100,000×) resolutions. Macro/micro/meso/nanoscale images have scale bars of 1 mm, 50 μm, 5 μm, and 500 nm, respectively.</p>
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<p>Relative expression of osteogenesis-related genes in human BMSCs cultured for 14 days on TCPS, smooth, anodized, or micro/nano-rough (MN) surfaces via RT-qPCR. Genes were normalized to GAPDH, and their relative expression compared to TCPS, determined using the 2<sup>−ΔΔCT</sup> method. Values presented are mean ± SE of twelve independent cultures per surface, pooled in duplicate with <span class="html-italic">n</span> of 6 per group. Groups were evaluated using analysis of variance (ANOVA) with Tukey post hoc test. Statistical significance was established at <span class="html-italic">p</span>-values equal to or less than 0.05 (* <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; **** <span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>Relative expression of anti-/pro-inflammatory genes in human BMSCs cultured for 14 days on TCPS, smooth, anodized, or micro/nano-rough (MN) surfaces via RT-qPCR. Genes related to innate and adaptive immune mechanisms related to inflammation, including genes that encode for cytokines/chemokines and inflammasome components with anti-inflammatory (top) and pro-inflammatory (bottom) effects, were analyzed. Fold changes to TCPS were normalized to GAPDH and relative expression determined using 2<sup>−ΔΔCT</sup> method. Values are presented as mean ± SE of twelve independent cultures per surface, pooled in duplicate with <span class="html-italic">n</span> of 6 per group. Groups were evaluated using analysis of variance (ANOVA) with Tukey post hoc test. Statistical significance was established at <span class="html-italic">p</span>-values equal to or less than 0.05 (* <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>Relative expression of extracellular matrix (ECM)-related genes related to integrin binding and cell adhesion in human BMSCs. Cells were cultured for 14 days on TCPS, smooth, anodized, or micro-/nano-rough (MN) surfaces via RT-qPCR. Representative genes related to integrin binding are on top, and components of ECM are shown in bottom row. Fold changes to TCPS were normalized to GAPDH and relative expression determined using 2<sup>−ΔΔCT</sup> method. Values are presented as mean ± SE of twelve independent cultures per surface, pooled in duplicate with <span class="html-italic">n</span> of 6 per group. Groups were evaluated using analysis of variance (ANOVA) with Tukey post hoc test. Statistical significance was established at <span class="html-italic">p</span>-values equal to or less than 0.05 (* <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; **** <span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>Comparison of 12,000 differentially expressed genes (DEGs) of human BMSCs grown in osteogenic media (OM), compared with BMSCs cultured on micro/nano-rough (MN) surfaces or TCPS in standard growth media: (<b>A</b>) Heatmap of sample z-scores clustered using Euclidean distance measurement. Red and green in heat map denote upregulated and downregulated genes, respectively, while gray denotes no significant difference between groups. (<b>B</b>) Principal component analysis (PCA) plot generated from 12,000 differentially expressed genes in hBMSCs grown for 14 days on TCPS in OM, TCPS in growth media, or MN surfaces in growth media, as determined by RNA-seq. Results from two independent experiments are shown.</p>
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<p>Comparison of 12,000 differentially expressed of genes (DEGs) of human BMSCs grown on TCPS in osteogenic media (OM), or BMSCs cultured on micro/nano-rough (MN) surfaces in growth media, compared to cells on TCPS in growth media. (<b>A</b>) Venn diagram displaying overlap of differentially expressed genes, showing overlap between OM and MN cultures. (<b>B</b>) Volcano plot of MN vs. TCPS genes with Log2 fold change greater than 2 and adjusted <span class="html-italic">p</span>-value less than 0.05. (<b>C</b>) Volcano plot of OM vs. TCPS genes with Log2 fold change greater than 2 and adjusted <span class="html-italic">p</span>-value less than 0.05. Red and blue denote upregulated and downregulated genes, respectively, while gray denotes no significant difference between groups.</p>
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<p>Functional enrichment analysis of genes expressed by BMSCs grown on TCPS in growth media (TCPS), TCPS in osteogenic media (OM), and micro/nano-rough Ti6Al4V in growth media (MN). The enriched pathways were visualized using a barplot for each pairwise comparison of treatments: (<b>A</b>) MN vs. TCPS, (<b>B</b>) OM vs. TCPS, and (<b>C</b>) MN vs. OM. (<b>D</b>) The Venn diagrams were created by determining the overlapping pathways between OM vs. TCPS and MN vs. TCPS.</p>
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