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18 pages, 665 KiB  
Article
Perceived Greenwashing and Its Impact on the Green Image of Brands
by Jui-Che Tu, Yang Cui, Lixia Liu and Chun Yang
Sustainability 2024, 16(20), 9009; https://doi.org/10.3390/su16209009 (registering DOI) - 17 Oct 2024
Abstract
In contemporary society, the growing attention paid to environmental protection and sustainable development has led to an increasing demand for green products. To meet this demand, companies have widely adopt green marketing strategies aimed at attracting consumers through environmental attributes. However, the phenomenon [...] Read more.
In contemporary society, the growing attention paid to environmental protection and sustainable development has led to an increasing demand for green products. To meet this demand, companies have widely adopt green marketing strategies aimed at attracting consumers through environmental attributes. However, the phenomenon of “greenwashing”, where companies exaggerate or mislead the public about their environmental actions, undermines consumer trust and damages brand reputation. This study explores the impact of brands’ green marketing strategies on consumers’ perception of greenwashing and green brand image through in-depth interviews and surveys. Initially, four key dimensions of brand green marketing were identified through interviews with 40 experts and industry stakeholders: products and services, communication, relationships and interaction, and commitment and values. Subsequently, data from 325 valid survey responses were collected online, and the hypotheses were tested using factor analysis and structural equation modeling. The results indicate that communication, relationships and interaction, and commitment and values effectively reduce greenwashing perception and, through this mediation, influence green brand image. This finding underscores the importance of brands avoiding false advertising in green marketing and ensuring the authenticity of their environmental information to maintain and enhance their green image. Full article
7 pages, 3688 KiB  
Article
Ultrasound-Guided Approach to the Distal Tarsal Tunnel: Implications for Healthcare Research on the Medial Plantar Nerve, Lateral Plantar Nerve and Inferior Calcaneal Nerve (Baxter’s Nerve)
by Alejandro Fernández-Gibello, Gabriel Camuñas Nieves, Ruth Liceth Jara Pacheco, Mario Fajardo Pérez and Felice Galluccio
Healthcare 2024, 12(20), 2071; https://doi.org/10.3390/healthcare12202071 (registering DOI) - 17 Oct 2024
Abstract
Background/Objectives: The tibial nerve, commonly misnamed the “posterior tibial nerve”, branches into four key nerves: the medial plantar, lateral plantar, inferior calcaneal (Baxter’s nerve), and medial calcaneal branches. These nerves are integral to both the sensory and motor functions of the foot. Approximately [...] Read more.
Background/Objectives: The tibial nerve, commonly misnamed the “posterior tibial nerve”, branches into four key nerves: the medial plantar, lateral plantar, inferior calcaneal (Baxter’s nerve), and medial calcaneal branches. These nerves are integral to both the sensory and motor functions of the foot. Approximately 15% of adults with foot issues experience heel pain, frequently stemming from neural origins, such as tarsal tunnel syndrome (TTS). TTS diagnosis remains challenging due to a high false negative rate in neurophysiological studies. This study aims to improve the understanding and diagnosis of distal tarsal tunnel pathology to enable more effective treatments, including platelet-rich plasma, hydrodissections, radiofrequencies, and prolotherapy. Methods: Ultrasound-guided techniques were employed to examine the distal tarsal tunnel using the Heimkes triangle for optimal probe placement. Results: The results indicate that the tunnel consists of two chambers separated by the interfascicular septum, housing the medial, lateral plantar, and inferior calcaneal nerves. Successful interventions depend on precise visualization and patient positioning. This study emphasizes the importance of avoiding the calcaneus periosteum to reduce discomfort. Conclusions: Standardizing nerve involvement classification in TTS is difficult without robust neurophysiological studies. The accurate targeting of nerve branches is essential for effective treatment. Full article
(This article belongs to the Special Issue Research on Podiatric Medicine and Healthcare)
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Figure 1
<p>Image (<b>a</b>) shows the dissection of a tarsal tunnel in which the laciniate ligament and the proximal compartments have been removed, leaving the distal tunnel with the key structure (deep fascia of the hallux abductor) with an asterisk. Points A, B, and C show the Heimkes triangle and line A-B shows the area where the ultrasound probe is to be positioned. ABDH (abductor hallucis), PF (central component of the plantar fascia), ICMS (intercompartmental medial septum), TPT (tibialis posterior tendon), FDLT (flexor digitorum longus tendon), 1 (medial plantar nerve), 2 (lateral plantar nerve), 3 (Baxter’s nerve), 4 (medial calcaneal branch). (<b>b</b>) shows a cranio-caudal view of the distal tarsal tunnel and its two chambers, the superior and inferior, separated by the interfascicular septum (red asterisk) and covered by the deep fascia of the ABDH (black asterisk).</p>
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<p>Image (<b>a</b>) shows the dissection of a tarsal tunnel in which the laciniate ligament and the proximal compartments have been removed, leaving the distal tunnel with the key structure (deep fascia of the hallux abductor) with an asterisk. Points A, B, and C show the Heimkes triangle and line A-B shows the area where the ultrasound probe is to be positioned. ABDH (abductor hallucis), PF (central component of the plantar fascia), ICMS (intercompartmental medial septum), TPT (tibialis posterior tendon), FDLT (flexor digitorum longus tendon), 1 (medial plantar nerve), 2 (lateral plantar nerve), 3 (Baxter’s nerve), 4 (medial calcaneal branch). (<b>b</b>) shows a cranio-caudal view of the distal tarsal tunnel and its two chambers, the superior and inferior, separated by the interfascicular septum (red asterisk) and covered by the deep fascia of the ABDH (black asterisk).</p>
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<p>In image (<b>a</b>), you can see the illustrated version of the ultrasound in image (<b>b</b>), where we find the ABDH (abductor hallucis), the mpn (medial plantar nerve) in the upper chamber, the lpn (lateral plantar nerve) and bn (Baxter’s nerve) in the inferior chamber with the quadratus plantar (QP) in the deepest aspect, sonographically speaking, or lateral in the anatomical sense. Delimiting these structures, we find the deep fascia of the ABDH (white asterisk) and the interfascicular septum (red asterisk) both forming an “italic t”. Finally, in image (<b>c</b>), we have a coronal section of the foot and ankle where the distal tarsal tunnel is shown in a black box, and in red circles, the compression points 1 and 2 of Baxter’s nerve, of which we have only treated 1, since this is typical of the distal tarsal tunnel.</p>
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<p>(<b>a</b>) shows the proximal–distal approach to the medial plantar nerve in the upper chamber, while (<b>b</b>) shows the lateral plantar nerve, and (<b>c</b>) illustrates Baxter’s nerve in the lower chamber. The asterisk shows the location of the medial plantar nerve, lateral plantar nerve, and inferior calcaneal nerve in images (<b>a</b>–<b>c</b>), FHLT (Flexor hallucis longus tendon).</p>
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21 pages, 4795 KiB  
Article
Robust Leader–Follower Formation Control Using Neural Adaptive Prescribed Performance Strategies
by Fengxi Xie, Guozhen Liang and Ying-Ren Chien
Mathematics 2024, 12(20), 3259; https://doi.org/10.3390/math12203259 - 17 Oct 2024
Abstract
This paper introduces a novel leader–follower formation control strategy for autonomous vehicles, aimed at achieving precise trajectory tracking in uncertain environments. The approach is based on a graph guidance law that calculates the desired yaw angles and velocities for follower vehicles using the [...] Read more.
This paper introduces a novel leader–follower formation control strategy for autonomous vehicles, aimed at achieving precise trajectory tracking in uncertain environments. The approach is based on a graph guidance law that calculates the desired yaw angles and velocities for follower vehicles using the leader’s reference trajectory, improving system stability and predictability. A key innovation is the development of a Neural Adaptive Prescribed Performance Controller (NA-PPC), which incorporates a Radial Basis Function Neural Network (RBFNN) to approximate nonlinear system dynamics and enhances disturbance estimation accuracy. The proposed method enables high-precision trajectory tracking and formation maintenance under random disturbances, which are vital for autonomous vehicle logistics and detection technologies. Leveraging a graph-based guidance law reduces control complexity and improves robustness against external disturbances. The inclusion of second-order filters and adaptive RBFNNs further enhances nonlinear error handling, improving control performance, stability, and accuracy. The integration of guidance laws, leader–follower control strategies, backstepping techniques, and RBFNNs creates a robust formation control system capable of maintaining performance under dynamic conditions. Comprehensive computer simulations validate the effectiveness of this controller, highlighting its potential to advance autonomous vehicle formation control. Full article
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<p>Vehicle model.</p>
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<p>Proposed formation controller design.</p>
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<p>Formation control of the geometric relationship between leader and <span class="html-italic">i</span>-th follower.</p>
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<p>An example of external disturbance <math display="inline"><semantics> <mrow> <mi>χ</mi> <mo>(</mo> <mi>t</mi> <mo>)</mo> </mrow> </semantics></math>.</p>
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<p>Trajectory of formation with different cases: (<b>a</b>) Without PPC method and (<b>b</b>) with PPC method.</p>
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<p>Trajectory tracking error of x-axis with different methods: (<b>a</b>) without PPC method and (<b>b</b>) with PPC method.</p>
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<p>Trajectory tracking error of x-axis with different methods: (<b>a</b>) without PPC method and (<b>b</b>) with PPC method.</p>
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<p>Trajectory tracking error of <span class="html-italic">y</span>-axis with different methods: (<b>a</b>) Without PPC and (<b>b</b>) with PPC.</p>
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<p>Steering angle error of formation with different methods: (<b>a</b>) Without PPC and (<b>b</b>) with PPC.</p>
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<p>Vehicle velocity with different methods: (<b>a</b>) Without PPC and (<b>b</b>) with PPC.</p>
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<p>Vehicle velocity with different methods: (<b>a</b>) Without PPC and (<b>b</b>) with PPC.</p>
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<p>Control inputs of Vehicle 2 with different methods: (<b>a</b>) Without PPC (<b>b</b>) with PPC.</p>
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<p>Control inputs of Vehicle 3 with different methods: (<b>a</b>) Without PPC and (<b>b</b>) with PPC.</p>
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<p>Control inputs of Vehicle 4 with different methods: (<b>a</b>) Without PPC and (<b>b</b>) with PPC.</p>
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<p>Control inputs of Vehicle 4 with different methods: (<b>a</b>) Without PPC and (<b>b</b>) with PPC.</p>
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<p>Control inputs of Vehicle 5 with different methods: (<b>a</b>) Without PPC and (<b>b</b>) with PPC.</p>
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<p>Control inputs of Vehicle 6 with different methods: (<b>a</b>) Without PPC and (<b>b</b>) with PPC.</p>
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30 pages, 609 KiB  
Article
The Calibrated Safety Constraints Optimal Power Flow for the Operation of Wind-Integrated Power Systems
by Kai-Hung Lu, Wenjun Qian, Yuesong Jiang and Yi-Shun Zhong
Processes 2024, 12(10), 2272; https://doi.org/10.3390/pr12102272 - 17 Oct 2024
Abstract
As the penetration of renewable energy sources (RESs), particularly wind power, continues to rise, the uncertainty in power systems increases. This challenges traditional optimal power flow (OPF) methods. This paper proposes a Calibrated Safety Constraints Optimal Power Flow (CSCOPF) model that uses the [...] Read more.
As the penetration of renewable energy sources (RESs), particularly wind power, continues to rise, the uncertainty in power systems increases. This challenges traditional optimal power flow (OPF) methods. This paper proposes a Calibrated Safety Constraints Optimal Power Flow (CSCOPF) model that uses the Improved Acceleration Coefficient-Based Bee Swarm algorithm (IACBS) in combination with the equivalent current injection (ECI) model. The proposed method addresses key challenges in wind-integrated power systems by ensuring preventive safety scheduling and enabling effective power incident safety analysis (PISA). This improves system reliability and stability. This method incorporates mixed-integer programming, with continuous and discrete variables representing power outputs and control mechanisms. Detailed numerical simulations were conducted on the IEEE 30-bus test system, and the feasibility of the proposed method was further validated on the IEEE 118-bus test system. The results show that the IACBS algorithm outperforms the existing methods in both computational efficiency and robustness. It achieves lower generation costs and faster convergence times. Additionally, the CSCOPF model effectively prevents power grid disruptions during critical incidents, ensuring that wind farms remain operational within predefined safety limits, even in fault scenarios. These findings suggest that the CSCOPF model provides a reliable solution for optimizing power flow in renewable energy-integrated systems, significantly contributing to grid stability and operational safety. Full article
9 pages, 209 KiB  
Article
Risk Factors Associated with Unplanned Hospitalization Among Long-Term Care Facility Residents: A Retrospective Study in Central Taiwan
by Chiu-Hsiang Lee, Yu-An Chen, Chiu-Ming Yang, Kuang-Hua Huang, Tung-Han Tsai, Yuanmay Chang and Shwn-Huey Shieh
Healthcare 2024, 12(20), 2069; https://doi.org/10.3390/healthcare12202069 - 17 Oct 2024
Abstract
Most residents of long-term care facilities (LTCFs) are patients with chronic diseases requiring long-term care. Unplanned hospitalization of older and frailer residents from LTCFs reduces their mobility and increases the number of infections, complications, and falls that might lead to severe disability or [...] Read more.
Most residents of long-term care facilities (LTCFs) are patients with chronic diseases requiring long-term care. Unplanned hospitalization of older and frailer residents from LTCFs reduces their mobility and increases the number of infections, complications, and falls that might lead to severe disability or death. This study aimed to identify the critical risk factors associated with unplanned hospitalization among LTCF residents in Taiwan, providing insights that could inform better care practices in similar settings globally. A retrospective study was conducted using inpatient data from a medical center in central Taiwan, covering the period from 2011 to 2019. A total of 1220 LTCF residents were matched with general patients using propensity score matching. Multiple logistic regression analyses were performed to identify factors associated with unplanned hospitalization, controlling for relevant variables. LTCF residents had a significantly higher risk of unplanned hospitalization compared to general patients (OR = 1.44, 95% CI = 1.21–1.73). Key risk factors included advanced age (≥85 years, OR = 1.25, 95% CI = 1.02–1.54), the presence of comorbidities such as diabetes (OR = 1.17, 95% CI = 1.03–1.33) and renal failure (OR = 1.63, 95% CI = 1.42–1.86), high fall risk (OR = 2.67, 95% CI = 2.30–3.10), and being bedridden (OR = 6.55, 95% CI = 5.48–7.85). The presence of a tracheostomy tube also significantly increased hospitalization risk (OR = 1.73, 95% CI = 1.15–2.59). LTCF residents are at a higher risk of unplanned hospitalization, particularly those with specific comorbidities, physical limitations, and indwelling medical devices. These findings underscore the need for targeted interventions to manage these risks, potentially improving care outcomes for LTCF residents globally. Full article
22 pages, 1524 KiB  
Review
Insights into Metabolic Reprogramming in Tumor Evolution and Therapy
by Ching-Feng Chiu, Jonathan Jaime G. Guerrero, Ric Ryan H. Regalado, Ma. Joy B. Zamora, Jiayan Zhou, Kin Israel Notarte, Yu-Wei Lu, Paolo C. Encarnacion, Cidne Danielle D. Carles, Edrian M. Octavo, Dan Christopher I. Limbaroc, Charupong Saengboonmee and Shih-Yi Huang
Cancers 2024, 16(20), 3513; https://doi.org/10.3390/cancers16203513 - 17 Oct 2024
Abstract
Background: Cancer remains a global health challenge, characterized not just by uncontrolled cell proliferation but also by the complex metabolic reprogramming that underlies its development and progression. Objectives: This review delves into the intricate relationship between cancer and its metabolic alterations, drawing an [...] Read more.
Background: Cancer remains a global health challenge, characterized not just by uncontrolled cell proliferation but also by the complex metabolic reprogramming that underlies its development and progression. Objectives: This review delves into the intricate relationship between cancer and its metabolic alterations, drawing an innovative comparison with the cosmological concepts of dark matter and dark energy to highlight the pivotal yet often overlooked role of metabolic reprogramming in tumor evolution. Methods: It scrutinizes the Warburg effect and other metabolic adaptations, such as shifts in lipid synthesis, amino acid turnover, and mitochondrial function, driven by mutations in key regulatory genes. Results: This review emphasizes the significance of targeting these metabolic pathways for therapeutic intervention, outlining the potential to disrupt cancer’s energy supply and signaling mechanisms. It calls for an interdisciplinary research approach to fully understand and exploit the intricacies of cancer metabolism, pointing toward metabolic reprogramming as a promising frontier for developing more effective cancer treatments. Conclusion: By equating cancer’s metabolic complexity with the enigmatic nature of dark matter and energy, this review underscores the critical need for innovative strategies in oncology, highlighting the importance of unveiling and targeting the “dark energy” within cancer cells to revolutionize future therapy and research. Full article
(This article belongs to the Section Methods and Technologies Development)
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<p>A comparison of the major metabolic pathways in (<b>A</b>) normal and (<b>B</b>) cancer cells. In normal cells (<b>A</b>), glucose enters via GLUT transporters, fueling glycolysis and predominantly generating ATP through oxidative phosphorylation (OXPHOS) in the mitochondria. Fatty acid oxidation and glutaminolysis also contribute to ATP production and lipid synthesis. Pathways with relatively low activity, such as lactate production, are indicated by dashed lines. In contrast, cancer cells (<b>B</b>) demonstrate increased glucose uptake via upregulated GLUT transporters, resulting in enhanced glycolysis and the Warburg effect, where pyruvate is converted to lactate even in the presence of oxygen. This metabolic reprogramming supports rapid ATP production and proliferation. Despite the dominance of the Warburg effect, minimal TCA cycle activity and OXPHOS are retained, as indicated by the dashed lines. Abbreviations: glucose transporter type 1 (GLUT1); Monocarboxylate Transporter (MCT); adenosine triphosphate (ATP); mammalian target of rapamycin (mTOR); α-Ketoglutarate (α-KG); branched-chain amino acids (BCAAs); Solute Carrier Family 7 Member 5 (SLC7A5); Solute Carrier Family 1 Member 5 (SLC1A5); Fatty Acid Transport Protein (FATP); Plasma Membrane Fatty Acid-Binding Protein (FABPpm).</p>
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<p>An overview of the major metabolic pathways at work within cancer cells. Cell survival, growth, and proliferation require glucose to generate ATP, lipids, and amino acids through glycolysis, alongside other downstream reactions and pathways, including the pentose phosphate pathway, glutaminolysis, lipid synthesis, and branched-chain amino acid (BCAA) metabolism. The Warburg effect, characterized by increased glucose uptake and lactate production despite adequate oxygen, highlights metabolic reprogramming, supporting rapid tumor growth and survival even under oxidative conditions. The mTOR signaling pathway regulates cell growth, proliferation, survival, and cytoskeletal organization in response to insulin, growth factors, and other metabolic and cellular cues. Additionally, p53 plays an important role in promoting ATP production, facilitating citric acid cycle (also referred to as the TCA cycle or Krebs cycle) and glutamate synthesis, while regulating glycolysis and lipid synthesis. Dysregulation of mTOR signaling and p53 has been implicated in numerous diseases, including cancer and metabolic disorders. Moreover, the metabolic processes of cancer cells operate in distinct ways depending on the availability of nutrients. In situations where nutrients are abundant (nutrient-replete conditions), there is a focus on nucleotide production, lipid generation, and the utilization of glutamine. Conversely, under nutrient-deprived conditions, cancer cells favor fatty acid oxidation, acetate breakdown, the utilization of BCAAs, and glutaminolysis related to macropinocytosis and autophagy. Understanding the metabolic adaptations of cancer cells to diverse nutrient environmental conditions is vital for developing targeted therapies to combat disease progression. Abbreviations: Pentose phosphate pathway. glucose-6-phosphate dehydrogenase (G6PD); Ribulose 5-phosphate (Ribulose-5P); Xylulose 5-phosphate (Xylulose-5P); Ribose 5-phosphate (Ribose-5P); Glyceraldehyde 3-phosphate (G3P); Sedoheptulose 7-phosphate (sedoheptulose-7P); Transaldolase (TALDO); Erythrose 4-phosphate (Erythrose-4P); Fructose 6-phosphate (Fructose 6-p). Glycolysis. glucose-6-phosphate dehydrogenase (G6PD); Fructose 6-phosphate (Fructose 6-p); Fructose 1,6-biphosphate (Fructose 1,6-biP); Fructose 2,6-biphosphate (Fructose 2,6-biP); Glyceraldehyde 3-phosphate (GA3P); Dihydroxyacetone phosphate (DHAP); Glyceraldehyde-3-phosphate dehydrogenase (GAPDH); Phosphoglycerate mutase (PGAM); Pyruvate kinase M2 (PKM2); Lactate dehydrogenase (LDH). mTOR pathway. Phosphatidylinositol-3 kinase (PI3K); Protein kinase B (AKT); Rat sarcoma (Ras); Rapidly Accelerated Fibrosarcoma (Raf); Mitogen-Activated Protein Kinase (MEK); Extracellular Signal-Regulated Kinase (ERK); p90 Ribosomal S6 Kinase (RSK); Tuberous Sclerosis Complex1/2 (TSC1/2); Ras Homolog Enriched in Brain (Rheb); Guanosine Triphosphate (GTP); Ras-related GTP binding A/B (Rag A/B); Ras-related GTP binding C/D (Rag C/D); Guanosine Diphosphate (GDP); mammalian target of rapamycin (mTOR); Hypoxia-Inducible Factor 1 (HIF-1). branched-chain amino acid (BCAA). α-ketoglutarate (α-KG); glutamine (Gln); glutamate (Glu); Branched-chain Aminotransferases (BCAT); 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA); α-ketoisocaproate (KIC); branched-chain amino acid Aminotransferase (BCAT). Glutaminolysis. glutaminase (GLS); Glutamate Dehydrogenase (GLUD); Sodium-Dependent Neutral Amino Acid Transporter (SLC1A5). Lipid Synthesis. 3-hydroxyl3-methyl-glutaryl-coenzyme A reductase (HMG-CoA); Acetyl-CoA Carboxylase (ACACA); fatty acid synthase (FASN); 3-hydroxy-3-methylglutaryl-CoA Reductase (HMGCR); Farnesyl Pyrophosphate (FPP); Stearoyl-Coa Desaturase (SCD); Monounsaturated Fatty Acid (MUFA); Polyunsaturated Fatty Acid (PUFA).</p>
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13 pages, 1805 KiB  
Article
Predicting Survival Status in COVID-19 Patients: Machine Learning Models Development with Ventilator-Related and Biochemical Parameters from Early Stages: A Pilot Study
by Shin-Ho Chou, Cheng-Yu Tsai, Wen-Hua Hsu, Chi-Li Chung, Hsin-Yu Li, Zhihe Chen, Rachel Chien and Wun-Hao Cheng
J. Clin. Med. 2024, 13(20), 6190; https://doi.org/10.3390/jcm13206190 - 17 Oct 2024
Abstract
Objective: Coronavirus disease 2019 (COVID-19) can cause intubation and ventilatory support due to respiratory failure, and extubation failure increases mortality risk. This study, therefore, aimed to explore the feasibility of using specific biochemical and ventilator parameters to predict survival status among COVID-19 [...] Read more.
Objective: Coronavirus disease 2019 (COVID-19) can cause intubation and ventilatory support due to respiratory failure, and extubation failure increases mortality risk. This study, therefore, aimed to explore the feasibility of using specific biochemical and ventilator parameters to predict survival status among COVID-19 patients by using machine learning. Methods: This study included COVID-19 patients from Taipei Medical University-affiliated hospitals from May 2021 to May 2022. Sequential data on specific biochemical and ventilator parameters from days 0–2, 3–5, and 6–7 were analyzed to explore differences between the surviving (successfully weaned off the ventilator) and non-surviving groups. These data were further used to establish separate survival prediction models using random forest (RF). Results: The surviving group exhibited significantly lower mean C-reactive protein (CRP) levels and mean potential of hydrogen ions levels (pH) levels on days 0–2 compared to the non-surviving group (CRP: non-surviving group: 13.16 ± 5.15 ng/mL, surviving group: 10.23 ± 5.15 ng/mL; pH: non-surviving group: 7.32 ± 0.07, survival group: 7.37 ± 0.07). Regarding the survival prediction performanace, the RF model trained solely with data from days 0–2 outperformed models trained with data from days 3–5 and 6–7. Subsequently, CRP, the partial pressure of carbon dioxide in arterial blood (PaCO2), pH, and the arterial oxygen partial pressure to fractional inspired oxygen (P/F) ratio served as primary indicators in survival prediction in the day 0–2 model. Conclusions: The present developed models confirmed that early biochemical and ventilatory parameters—specifically, CRP levels, pH, PaCO2, and P/F ratio—were key predictors of survival for COVID-19 patients. Assessed during the initial two days, these indicators effectively predicted the likelihood of successful weaning of from ventilators, emphasizing their importance in early management and improved outcomes in COVID-19-related respiratory failure. Full article
(This article belongs to the Section Pulmonology)
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<p>Illustrates the performance metrics of models trained with the following three different periods: Days 0–2, Days 3–5, and Days 6–7. The metrics include Error Rates (ERRs), Accuracy, F1 Scores, and Area Under the Receiver Operating Characteristic Curve (AUROC).</p>
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<p>Shows the feature importance for predicting survival (with successful weaning) versus non-survival using data from Days (<b>A</b>) 0–2, (<b>B</b>) 3–5, and (<b>C</b>) 6–7. During days 0–2, CRP is the most important feature, followed by PaCO<sub>2</sub>, pH, and P/F ratio.</p>
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13 pages, 1771 KiB  
Article
Single-Stage Image-Guided Percutaneous Ablation with Thoracoscopic Resection for Multiple Pulmonary Lesions in a Hybrid Operating Room: A Retrospective Study
by Ling-Kai Chang, Po-Keng Su, Pak-Si Chan, Shwetambara Malwade, Wen-Yuan Chung and Shun-Mao Yang
Cancers 2024, 16(20), 3512; https://doi.org/10.3390/cancers16203512 - 17 Oct 2024
Abstract
Background: Different approaches are required in treating patients with multiple pulmonary lesions. A multistage procedure may increase the risk of complications and patient discomfort. This study reports an initial experience with single-stage management of multiple lung lesions using percutaneous ablation with thoracoscopic resection [...] Read more.
Background: Different approaches are required in treating patients with multiple pulmonary lesions. A multistage procedure may increase the risk of complications and patient discomfort. This study reports an initial experience with single-stage management of multiple lung lesions using percutaneous ablation with thoracoscopic resection in a hybrid operating room (HOR). Methods: We retrospectively evaluated patients who underwent combined ablation and resection in an HOR between May 2022 and July 2024. All patients received a single anesthesia via endotracheal tube intubation. The clinical data, operative findings, and pathological characteristics of the lung nodules were recorded. Results: A total of 22 patients were enrolled in this study. Twenty patients underwent unilateral procedures, while the other two patients underwent bilateral procedures. Ablations were performed before lung resection in 21 patients; only 1 patient underwent surgery first. The median global operating room time was 227.0 min. The median total radiation dose (dose area product) was 14,076 μGym2. The median hospital postoperative length of stay was 2 days. Conclusions: The single-stage procedure of percutaneous ablation with thoracoscopic resection under general anesthesia in an HOR is feasible and safe. This procedure is an alternative method for managing multiple pulmonary lesions. Full article
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Figure 1
<p>Single-stage synchronized procedures of ablation and VATS in an HOR. (<b>A</b>) The C-arm projects the laser cross to insert the coaxial needle for the ablation procedure; (<b>B</b>) insertion of the ablation needle using arm support under a progressive view augmented fluoroscopy; (<b>C</b>) post-ablation CT showing the ablation zone while the needle was still inside the lesion; (<b>D</b>) confirmation CT scan for checking the stamped area alignment with the actual lesion location; (<b>E</b>) thoracoscopic surgery using a uniportal approach; (<b>F</b>) the dye-stamped area was identified to guide thoracoscopic resection. CT, computed tomography; VATS, video-assisted thoracic surgery; HOR, hybrid operating room.</p>
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<p>Demonstration of six cases from pre-ablation to resection. (<b>A</b>) Pre-ablation CT scan to indicate the location of the lesion to undergo ablation; (<b>B</b>) post-ablation CT showing the ablation zone and ablation needle in the zone; (<b>C</b>) CT to indicate the location of the lesion to undergo resection; (<b>D</b>) resected part of the lung showing that the lesion was successfully removed. CT, computed tomography.</p>
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<p>Combined ablation and wedge resection of the same pulmonary lobe. (<b>A</b>) Ablation placement after partial resection; (<b>B</b>) focal ablation zone away from the staple line; (<b>C</b>) post-procedure CT showed a staple line near the ablation zone; (<b>D</b>) post-procedure CT showed a staple line in the ablation zone.</p>
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19 pages, 1786 KiB  
Article
An Exploratory Study on the Efficacy and Inclusivity of AI Technologies in Diverse Learning Environments
by Michael Pin-Chuan Lin, Arita Li Liu, Eric Poitras, Maiga Chang and Daniel H. Chang
Sustainability 2024, 16(20), 8992; https://doi.org/10.3390/su16208992 - 17 Oct 2024
Abstract
This exploratory research conducted a thematic analysis of students’ experiences and utilization of AI tools by students in educational settings. We surveyed 87 undergraduates from two different educational courses at a comprehensive university in Western Canada. Nine integral themes that represent AI’s role [...] Read more.
This exploratory research conducted a thematic analysis of students’ experiences and utilization of AI tools by students in educational settings. We surveyed 87 undergraduates from two different educational courses at a comprehensive university in Western Canada. Nine integral themes that represent AI’s role in student learning and key issues with respect to AI have been identified. The study yielded three critical insights: the potential of AI to expand educational access for a diverse student body, the necessity for robust ethical frameworks to govern AI, and the benefits of personalized AI-driven support. Based on the results, a model is proposed along with recommendations for an optimal learning environment, where AI facilitates meaningful learning. We argue that integrating AI tools into learning has the potential to promote inclusivity and accessibility by making learning more accessible to diverse students. We also advocate for a shift in perception among educational stakeholders towards AI, calling for de-stigmatization of its use in education. Overall, our findings suggest that academic institutions should establish clear, empirical guidelines defining student conduct with respect to what is considered appropriate AI use. Full article
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<p>Codes and themes based on student responses.</p>
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<p>Frequency of AI-Related themes in student responses.</p>
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<p>Code co-occurrence Sankey diagram.</p>
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<p>A refined model representing an ideal ecosystem of AI use from student perspectives.</p>
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18 pages, 1593 KiB  
Article
Privacy-Preserving Handover Optimization Using Federated Learning and LSTM Networks
by Wei-Che Chien, Yu Huang, Bo-Yu Chang and Wu-Yuin Hwang
Sensors 2024, 24(20), 6685; https://doi.org/10.3390/s24206685 - 17 Oct 2024
Abstract
The rapid evolution of wireless communication systems necessitates advanced handover mechanisms for seamless connectivity and optimal network performance. Traditional algorithms, like 3GPP Event A3, often struggle with fluctuating signal strengths and dynamic user mobility, leading to frequent handovers and suboptimal resource utilization. This [...] Read more.
The rapid evolution of wireless communication systems necessitates advanced handover mechanisms for seamless connectivity and optimal network performance. Traditional algorithms, like 3GPP Event A3, often struggle with fluctuating signal strengths and dynamic user mobility, leading to frequent handovers and suboptimal resource utilization. This study proposes a novel approach combining Federated Learning (FL) and Long Short-Term Memory (LSTM) networks to predict Reference Signal Received Power (RSRP) and the strongest nearby Reference Signal Received Power (RSRP) signals. Our method leverages FL to ensure data privacy and LSTM to capture temporal dependencies in signal data, enhancing prediction accuracy. We develop a dynamic handover algorithm that adapts to real-time conditions, adjusting thresholds based on predicted signal strengths and historical performance. Extensive experiments with real-world data show our dynamic algorithm significantly outperforms the 3GPP Event A3 algorithm, achieving higher prediction accuracy, reducing unnecessary handovers, and improving overall network performance. In conclusion, this study introduces a data-driven, privacy-preserving approach that leverages advanced machine learning techniques, providing a more efficient and reliable handover mechanism for future wireless networks. Full article
(This article belongs to the Topic Innovation, Communication and Engineering)
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<p>Handover Decision Process with TTT and HOM.</p>
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<p>Proposed system structure.</p>
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<p>LSTM Model Structure.</p>
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<p>Explanation of the Process for Checking Ping-Pong Conditions.</p>
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<p>Our integral system flowchart.</p>
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<p>Clients’ Data Distribution, the circles in this figure are the outliers in each clients.</p>
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<p>Prediction result of heterogeneous federated learning.</p>
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<p>Prediction result of homogeneous federated learning.</p>
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<p>Prediction result of centralized LSTM model.</p>
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<p>95% Confidence Interval for RSRP Prediction.</p>
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<p>Comparison of Algorithm and HOPP Probability.</p>
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19 pages, 5830 KiB  
Article
Exploration of the Anti-Photoaging Mechanisms of Lactiplantibacillus plantarum TWK10 in a UVB-Induced Mouse Model
by Te-Hua Liu, Wan-Jyun Lin, Meng-Chun Cheng, Yi-Chen Cheng, Chia-Chia Lee, Jin-Seng Lin and Tsung-Yu Tsai
Appl. Sci. 2024, 14(20), 9497; https://doi.org/10.3390/app14209497 - 17 Oct 2024
Abstract
Functional foods have shown promise in mitigating skin aging. This study aimed to evaluate the effects of Lactiplantibacillus plantarum TWK10 (LPTWK10) and its spray-dried supernatant powder on ultraviolet B (UVB)-induced skin photoaging in female BALB/c nude mice. Over a 13-week period of UVB [...] Read more.
Functional foods have shown promise in mitigating skin aging. This study aimed to evaluate the effects of Lactiplantibacillus plantarum TWK10 (LPTWK10) and its spray-dried supernatant powder on ultraviolet B (UVB)-induced skin photoaging in female BALB/c nude mice. Over a 13-week period of UVB exposure and concurrent administration of high doses of LPTWK10 or its spray-dried fermentation supernatant, significant improvements were observed, skin wrinkles were notably reduced, transepidermal water loss rate decreased by 68.94–70.77%, and stratum corneum hydration increased by 76.97–112.24%. Furthermore, LPTWK10 was effective in reducing erythema and inflammation while enhancing skin lightness. Histological assessments revealed substantial reductions in epidermal hyperplasia and collagen degradation. Additionally, LPTWK10 was found to influence critical mechanisms associated with collagen metabolism and proinflammatory cytokine production. In summary, LPTWK10 attenuates photoaging through modulation of collagen metabolism and reduction in inflammatory responses, suggesting its potential as a functional ingredient for delaying photoaging. Full article
(This article belongs to the Section Food Science and Technology)
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<p>Effects of the administration of LPTWK10 or LPTWK10 spray-dried supernatant powders on dorsal wrinkles in UVB-induced nude mice. (<b>A</b>) NC (<b>B</b>) UVB (<b>C</b>) PC (<b>D</b>) LPLD (<b>E</b>) LPMD (<b>F</b>) LPHD (<b>G</b>) SPLD (<b>H</b>) SPMD (<b>I</b>) SPHD. Data are presented as mean ± SD (<span class="html-italic">n</span> = 7 or 8). UVB: ultraviolet B; NC: normal control; PC: positive control; LPLD, LPMD, and LPHD: administration of LPTWK10 at 2 × 10<sup>8</sup> CFU/kg bw/day, 2 × 10<sup>9</sup> CFU/kg bw/day and 2 × 10<sup>10</sup> CFU/kg bw/day, respectively; SPLD, SPMD and SPHD: administration of TWK10 spray-dried supernatant powders at 0.30 g/kg bw/day, 0.60 g/kg bw/day, and 1.20 g/kg bw/day, respectively. Red arrow: wrinkles.</p>
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<p>Effects of the administration of LPTWK10 or LPTWK10 spray-dried supernatant powders on (<b>A</b>) dorsal TEWL and (<b>B</b>) dorsal hydration of the stratum corneum in UVB-induced nude mice. Data are presented as mean ± SD (<span class="html-italic">n</span> = 7 or 8). Values with different uppercase letters were significantly different by Duncan’s multiple range test (<span class="html-italic">p</span> &lt; 0.05). TEWL: transepidermal water loss; UVB: ultraviolet B; NC: normal control; PC: positive control; LPLD, LPMD and LPHD: administration of LPTWK10 viable cells at 2 × 10<sup>8</sup> CFU/kg bw/day, 2 × 10<sup>9</sup> CFU/kg bw/day and 2 × 10<sup>10</sup> CFU/kg bw/day, respectively; SPLD, SPMD and SPHD: administration of TWK10 spray-dried supernatant powders at 0.30 g/kg bw/day, 0.60 g/kg bw/day, and 1.20 g/kg bw/day, respectively.</p>
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<p>Effects of the administration of LPTWK10 or LPTWK10 spray-dried supernatant powders on dorsal (<b>A</b>) erythema (<b>B</b>) a* value (<b>C</b>) melanin and (<b>D</b>) lightness in UVB-induced nude mice. Data are presented as mean ± SD (<span class="html-italic">n</span> = 7−8). Values with different uppercase letters were significantly different in the same weeks by Duncan’s multiple range test (<span class="html-italic">p</span> &lt; 0.05). UVB: ultraviolet B; NC: normal control; PC: positive control; LPLD, LPMD and LPHD: administration of LPTWK10 viable cells at 2 × 10<sup>8</sup> CFU/kg bw/day, 2 × 10<sup>9</sup> CFU/kg bw/day and 2 × 10<sup>10</sup> CFU/kg bw/day, respectively; SPLD, SPMD and SPHD: administration of LPTWK10 spray-dried supernatant powders at 0.30 g/kg bw/day, 0.60 g/kg bw/day, and 1.20 g/kg bw/day, respectively.</p>
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<p>Effects of the administration of LPTWK10 or LPTWK10 spray-dried supernatant powders on dorsal (<b>A</b>) TNF-α, (<b>B</b>) IL-6, and (<b>C</b>) IL-1β levels in UVB-induced nude mice. Data are presented as mean ± SD (<span class="html-italic">n</span> = 7 or 8). Values with different uppercase letters were significantly different by Duncan’s multiple range test (<span class="html-italic">p</span> &lt; 0.05). TNF-α: tumor necrosis factor-α; IL-6: interleukin-6; IL-1β: interleukin-1β; UVB: ultraviolet B; NC: normal control; PC: positive control; LPLD, LPMD and LPHD: administration of LPTWK10 viable cells at 2 × 10<sup>8</sup> CFU/kg bw/day, 2 × 10<sup>9</sup> CFU/kg bw/day and 2 × 10<sup>10</sup> CFU/kg bw/day, respectively; SPLD, SPMD and SPHD: administration of LPTWK10 spray-dried supernatant powders at 0.30 g/kg bw/day, 0.60 g/kg bw/day, and 1.20 g/kg bw/day, respectively.</p>
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<p>Effects of the administration of LPTWK10 or LPTWK10 spray-dried supernatant powders on dorsal (<b>A</b>) Type I procollagen, (<b>B</b>) Type III procollagen, (<b>C</b>) Type III procollagen/Type I procollagen, (<b>D</b>) MMP-1, (<b>E</b>) MMP-9 and (<b>F</b>) AP-1 levels in UVB-induced nude mice. Data are presented as mean ± SD (<span class="html-italic">n</span> = 7 or 8). Values with different uppercase letters were significantly different by Duncan’s multiple range test (<span class="html-italic">p</span> &lt; 0.05). UVB: ultraviolet B; NC: normal control; PC: positive control; LPLD, LPMD and LPHD: administration of LPTWK10 viable cells at 2 × 10<sup>8</sup> CFU/kg bw/day, 2 × 10<sup>9</sup> CFU/kg bw/day and 2 × 10<sup>10</sup> CFU/kg bw/day, respectively; SPLD, SPMD and SPHD: administration of LPTWK10 spray-dried supernatant powders at 0.30 g/kg bw/day, 0.60 g/kg bw/day, and 1.20 g/kg bw/day, respectively.</p>
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<p>Effects of the administration of LPTWK10 viable cells or LPTWK10 spray-dried supernatant powders on dorsal histopathological findings (<b>A</b>–<b>I</b>) H&amp;E stain, (<b>J</b>) epidermis thickness level and (<b>K</b>–<b>S</b>) MT stain in UVB-induced nude mice. (<b>A</b>,<b>K</b>) NC, (<b>B</b>,<b>L</b>) UVB, (<b>C</b>,<b>M</b>) PC, (<b>D</b>,<b>N</b>) LPLD, (<b>E</b>,<b>O</b>) LPMD, (<b>F</b>,<b>P</b>) LPHD, (<b>G</b>,<b>Q</b>) SPLD, (<b>H</b>,<b>R</b>) SPMD, and (<b>I</b>,<b>S</b>) SPHD. Original magnification, 400×; scale bar = 100 μm. Data are presented as mean ± SD (<span class="html-italic">n</span> = 7 or 8). H&amp;E: hematoxylin and eosin; UVB: ultraviolet B; NC: normal control; PC: positive control; LPLD, LPMD and LPHD: administration of LPTWK10 viable cells at 2 × 10<sup>8</sup> CFU/kg bw/day, 2 × 10<sup>9</sup> CFU/kg bw/day and 2 × 10<sup>10</sup> CFU/kg bw/day, respectively; SPLD, SPMD and SPHD: administration of LPTWK10 spray-dried supernatant powders at 0.30 g/kg bw/day, 0.60 g/kg bw/day, and 1.20 g/kg bw/day, respectively. Black arrow: epidermis thickness. Values with different uppercase letters were significantly different by Duncan’s multiple range test (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Effects of the administration of LPTWK10 or LPTWK10 spray-dried supernatant powders on dorsal immunohistochemistry stain (claudin-1) in UVB-induced nude mice. (<b>A</b>) NC, (<b>B</b>) UVB, (<b>C</b>) PC, (<b>D</b>) LPLD, (<b>E</b>) LPMD, (<b>F</b>) LPHD, (<b>G</b>) SPLD, (<b>H</b>) SPMD, and (<b>I</b>) SPHD. Original magnification, 100×; scale bar = 200 μm. Data are presented as mean ± SD (<span class="html-italic">n</span> = 7 or 8). MT: Masson’s trichrome; UVB: ultraviolet B; NC: normal control; PC: positive control; LPLD, LPMD, and LPHD: administration of LPTWK10 viable cells at 2 × 10<sup>8</sup> CFU/kg bw/day, 2 × 10<sup>9</sup> CFU/kg bw/day and 2 × 10<sup>10</sup> CFU/kg bw/day, respectively; SPLD, SPMD and SPHD: administration of LPTWK10 spray-dried supernatant powders at 0.30 g/kg bw/day, 0.60 g/kg bw/day, and 1.20 g/kg bw/day, respectively. Black arrow: claudin-1 protein in the epidermis layer.</p>
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<p>Effects of the administration of LPTWK10 or LPTWK10 spray-dried supernatant powders on dorsal immunohistochemistry stain (laminin) in UVB-induced nude mice. (<b>A</b>) NC, (<b>B</b>) UVB, (<b>C</b>) PC, (<b>D</b>) LPLD, (<b>E</b>) LPMD, (<b>F</b>) LPHD, (<b>G</b>) SPLD, (<b>H</b>) SPMD, and (<b>I</b>) SPHD. Original magnification, 100×; scale bar = 200 μm. Data are presented as mean ± SD (<span class="html-italic">n</span> = 7 or 8). MT: Masson’s trichrome; UVB: ultraviolet B; NC: normal control; PC: positive control; LPLD, LPMD, and LPHD: administration of LPTWK10 viable cells at 2 × 10<sup>8</sup> CFU/kg bw/day, 2 × 10<sup>9</sup> CFU/kg bw/day and 2 × 10<sup>10</sup> CFU/kg bw/day, respectively; SPLD, SPMD and SPHD: administration of LPTWK10 spray-dried supernatant powders at 0.30 g/kg bw/day, 0.60 g/kg bw/day, and 1.20 g/kg bw/day, respectively. Black arrow: laminin protein in the basement membrane.</p>
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<p>Effects of the administration of LPTWK10 or LPTWK10 spray-dried supernatant powders on dorsal immunohistochemistry stain (type IV collagen) in UVB-induced nude mice. (<b>A</b>) NC, (<b>B</b>) UVB, (<b>C</b>) PC, (<b>D</b>) LPLD, (<b>E</b>) LPMD, (<b>F</b>) LPHD, (<b>G</b>) SPLD, (<b>H</b>) SPMD, and (<b>I</b>) SPHD. Original magnification, 100×; scale bar = 200 μm. Data are presented as mean ± SD (<span class="html-italic">n</span> = 7 or 8). MT: Masson’s trichrome; UVB: ultraviolet B; NC: normal control; PC: positive control; LPLD, LPMD and LPHD: administration of LPTWK10 viable cells at 2 × 10<sup>8</sup>, 2 × 10<sup>9</sup> and 2 × 10<sup>10</sup> CFU/kg bw/day, respectively; SPLD, SPMD and SPHD: administration of LPTWK10 spray-dried supernatant powders at 0.30, 0.60 and 1.20 g/kg bw/day, respectively. Black arrow: type IV collagen protein in the basement membrane.</p>
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21 pages, 6102 KiB  
Article
Mechanisms of Action of Sea Cucumber Triterpene Glycosides Cucumarioside A0-1 and Djakonovioside A Against Human Triple-Negative Breast Cancer
by Ekaterina S. Menchinskaya, Ekaterina A. Chingizova, Evgeny A. Pislyagin, Ekaterina A. Yurchenko, Anna A. Klimovich, Elena. A. Zelepuga, Dmitry L. Aminin, Sergey A. Avilov and Alexandra S. Silchenko
Mar. Drugs 2024, 22(10), 474; https://doi.org/10.3390/md22100474 - 17 Oct 2024
Abstract
Breast cancer is the most prevalent form of cancer in women worldwide. Triple-negative breast cancer is the most unfavorable for patients, but it is also the most sensitive to chemotherapy. Triterpene glycosides from sea cucumbers possess a high therapeutic potential as anticancer agents. [...] Read more.
Breast cancer is the most prevalent form of cancer in women worldwide. Triple-negative breast cancer is the most unfavorable for patients, but it is also the most sensitive to chemotherapy. Triterpene glycosides from sea cucumbers possess a high therapeutic potential as anticancer agents. This study aimed to identify the pathways triggered and regulated in MDA-MB-231 cells (triple-negative breast cancer cell line) by the glycosides cucumarioside A0-1 (Cuc A0-1) and djakonovioside A (Dj A), isolated from the sea cucumber Cucumaria djakonovi. Using flow cytometry, fluorescence microscopy, immunoblotting, and ELISA, the effects of micromolar concentrations of the compounds on cell cycle arrest, induction of apoptosis, the level of reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), and expression of anti- and pro-apoptotic proteins were investigated. The glycosides caused cell cycle arrest, stimulated an increase in ROS production, and decreased Δψm in MDA-MB-231 cells. The depolarization of the mitochondrial membrane caused by cucumarioside A0-1 and djakonovioside A led to an increase in the levels of APAF-1 and cytochrome C. This, in turn, resulted in the activation of caspase-9 and caspase-3 and an increase in the level of their cleaved forms. Glycosides also affected the expression of Bax and Bcl-2 proteins, which are associated with mitochondria-mediated apoptosis in MDA-MB-231 cells. These results indicate that cucumarioside A0-1 and djakonovioside A activate the intrinsic apoptotic pathway in triple-negative breast cancer cells. Additionally, it was found that treatment with Cuc A0-1 resulted in in vivo inhibition of tumor growth and metastasis of murine solid Ehrlich adenocarcinoma. Full article
(This article belongs to the Collection Marine Compounds and Cancer)
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Graphical abstract

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<p>Chemical structures of triterpene glycosides: cucumarioside A<sub>0</sub>-1 (<b>a</b>) and djakonovioside A (<b>b</b>) isolated from the sea cucumber <span class="html-italic">Cucumaria djakonovi</span>.</p>
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<p>Distribution of MDA-MB-231 cells according to the phases of the cell cycle after treatment with various concentrations of Cuc A<sub>0</sub>-1 and Dj A for 24 h.</p>
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<p>Visualization of cyclin B and A contents and cyclin-dependent kinases in MDA-MB-231 cells treated with triterpene glycosides Cuc A<sub>0</sub>-1 and Dj A at different concentrations. Representative Western blot membranes showing the effect of glycosides on cyclin and CDK protein expression levels (<b>a</b>). Processed data on cyclin B content in MDA-MB-231 cells treated with Cuc A<sub>0</sub>-1 (<b>b</b>). Processed data on cyclin A content in MDA-MB-231 cells treated with Dj A (<b>c</b>). Processed data on CDK-1 content in MDA-MB-231 cells treated with Cuc A<sub>0</sub>-1 (<b>d</b>). Processed data on CDK-2 content in MDA-MB-231 cells treated with Dj A (<b>e</b>). All data were normalized to the β-actin levels. Data are presented as means ± SEM. * <span class="html-italic">p</span> value &lt; 0.05 was considered significant.</p>
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<p>Analysis of apoptosis induced by triterpene glycosides in MDA-MB-231 cells after 24 h of incubation. Flow cytometry assay for Annexin V-FITC/PI staining (<b>a</b>). Quantitative calculation of the data obtained via flow cytometry: Cuc A<sub>0</sub>-1 (0.5 and 1 μM)—(<b>b</b>) and Dj A (1 and 2 μM)—(<b>c</b>). Data are presented as means ± SEM. <span class="html-italic">p</span> value &lt; 0.05 was considered significant. Apoptosis assay using Hoechst 33342 in a fluorescent microscopy analysis (<b>d</b>). Hoechst 33342 staining showed an increase in chromatin condensation and DNA fragmentation in apoptotic cells treated with Cuc A<sub>0</sub>-1 (1 μM) and Dj A (2 μM) compared with untreated control cells. Arrows indicate nuclei with condensed chromatin.</p>
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<p>Quantitative evaluation of ROS levels in MDA-MB-231 cells after incubation with Cuc A<sub>0</sub>-1 (<b>a</b>) and Dj A (<b>b</b>) for different times (6, 12, and 24 h) using the fluorescent dye H<sub>2</sub>DCF-DA. Glycosides Cuc A<sub>0</sub>-1 (<b>c</b>) and Dj A (<b>d</b>), at various concentrations, reduced the mitochondrial membrane potential (Δψm), as measured using the fluorescent dye TMRE. Data are presented as means ± SEM. * <span class="html-italic">p</span> value &lt; 0.05 was considered significant. Staining of MDA-MB-231 cells with the fluorescent dye JC-1 showed a change in the mitochondrial membrane potential (<b>e</b>).</p>
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<p>Western blot analysis of cytoplasmic proteins: apoptosis promoter Bax (<b>a</b>,<b>b</b>) and apoptosis inhibitor Bcl-2 (<b>a</b>,<b>c</b>) with β-actin as a protein loading control under the treatment of MDA-MB-231 cells with different concentrations of Cuc A<sub>0</sub>-1 and Dj A. Cytoplasmic protein levels were normalized to the control group (untreated cells). * <span class="html-italic">p</span> &lt; 0.05 compared with untreated MDA-MB-231 cells.</p>
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<p>Quantitative assessment of the contents of cytochrome C (<b>a</b>,<b>b</b>) and APAF-1 (<b>c</b>,<b>d</b>) in MDA-MB-231 cells after treatment with different concentrations of glycosides Cuc A<sub>0</sub>-1 (<b>a</b>,<b>c</b>) and Dj A (<b>b</b>,<b>d</b>) at different times (6, 12, and 24 h) using ELISA kits. * <span class="html-italic">p</span> &lt; 0.05 compared with untreated MDA-MB-231 cells.</p>
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<p>Caspase-3/7 activity in the control cells and cells treated with triterpene glycosides for 12 and 24 h was measured using the Muse™ Caspase-3/7 Kit and flow cytometry in MDA-MB-231 cells.</p>
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<p>Western blot analysis of apoptotic markers (<b>a</b>) and quantitative analysis of the levels of cleaved caspase-9 (<b>b</b>), cleaved caspase-3 (<b>c</b>), and cleaved PARP-1 (<b>d</b>) in MDA-MB-231 cells treated with different concentrations of Cuc A<sub>0</sub>-1 and Dj A. β-actin was used as a protein loading control (<b>a</b>). The levels of apoptotic markers were normalized to those of the control group (untreated cells). * <span class="html-italic">p</span> &lt; 0.05 compared to untreated MDA-MB-231 cells.</p>
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<p>Influence of Cuc A<sub>0</sub>-1 on the area (<b>a</b>) and integrated density (<b>b</b>) of the fluorescence zone detected by in vivo fluorescence imager, Fluor I. Effect of Cuc A<sub>0</sub>-1 (0.4 µg/mL) on tumor volume (<b>c</b>) and tumor growth index (<b>d</b>). The data are presented as a mean ± SEM (n = 7). Asterisks indicate the significance of the differences at <span class="html-italic">p</span> ≤ 0.05 * and <span class="html-italic">p</span> ≤ 0.01 ** according to one-factor analysis of variance (ANOVA) with Tukey’s correction.</p>
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<p>The visualization of tumor cells labeled with PKH800 NIR fluorescent dye using the fluorescence imager system, “Fluor I IN VIVO”, in untreated mice (<b>a</b>), mice treated with Cuc A<sub>0</sub>-1 in group II (<b>b</b>), mice treated with Cuc A<sub>0</sub>-1 in group III (<b>c</b>), and mice treated with doxorubicin in group IV (<b>d</b>). On day 12, the tumor area was visualized in live mice; afterward, the mice were euthanized, the skin was opened, and tumor cells were visualized again. Arrows indicate tumor metastasis in the abdominal cavity.</p>
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<p>Three-dimensional plot of cytotoxic activity (pIC<sub>50</sub>) dependence on the principal component values (PCA1–PCA3) calculated for 25 conformational forms of 20 glycosides tested against MDA-MB-231 cells. The glycosides demonstrating cytotoxic activity with IC<sub>50</sub> ≤ 10 μM were outlined as active and are marked in red, while inactive glycosides are marked in violet.</p>
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<p>The PLS QSAR model correlation plot reflecting the relationship of predicted and experimental cytotoxicity of the glycosides against MDA-MB-231 cells. The cytotoxic action was expressed as pIC<sub>50</sub>.</p>
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20 pages, 1119 KiB  
Review
The Neural Correlations of Olfactory Associative Reward Memories in Drosophila
by Yu-Chun Lin, Tony Wu and Chia-Lin Wu
Cells 2024, 13(20), 1716; https://doi.org/10.3390/cells13201716 - 17 Oct 2024
Abstract
Advancing treatment to resolve human cognitive disorders requires a comprehensive understanding of the molecular signaling pathways underlying learning and memory. While most organ systems evolved to maintain homeostasis, the brain developed the capacity to perceive and adapt to environmental stimuli through the continuous [...] Read more.
Advancing treatment to resolve human cognitive disorders requires a comprehensive understanding of the molecular signaling pathways underlying learning and memory. While most organ systems evolved to maintain homeostasis, the brain developed the capacity to perceive and adapt to environmental stimuli through the continuous modification of interactions within a gene network functioning within a broader neural network. This distinctive characteristic enables significant neural plasticity, but complicates experimental investigations. A thorough examination of the mechanisms underlying behavioral plasticity must integrate multiple levels of biological organization, encompassing genetic pathways within individual neurons, interactions among neural networks providing feedback on gene expression, and observable phenotypic behaviors. Model organisms, such as Drosophila melanogaster, which possess more simple and manipulable nervous systems and genomes than mammals, facilitate such investigations. The evolutionary conservation of behavioral phenotypes and the associated genetics and neural systems indicates that insights gained from flies are pertinent to understanding human cognition. Rather than providing a comprehensive review of the entire field of Drosophila memory research, we focus on olfactory associative reward memories and their related neural circuitry in fly brains, with the objective of elucidating the underlying neural mechanisms, thereby advancing our understanding of brain mechanisms linked to cognitive systems. Full article
(This article belongs to the Special Issue Drosophila: Contribution to Cell Research)
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<p>Overview of the associative water- (or sucrose-) reward paradigms. Before the conditioning process, flies were subjected to a period of water (or food) deprivation lasting from 16 to 24 h. The conditioning protocol involved approximately 50 thirsty (or hungry) flies positioned on the elevator of a T-maze. Initially, the flies were transferred to a CS tube, where an odor (odor A: OCT or MCH) was introduced for 2 min. Subsequently, after a 1 min break in exposure to fresh air, the flies were returned to the elevator and guided to the CS+ tube, which contained filter paper soaked in water (or sucrose) and a different odor (odor B: MCH or OCT) for another 2 min period. Memory retention was evaluated at specified intervals after the training session by offering the flies a choice between two distinct odors.</p>
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<p>Overview of the <span class="html-italic">Drosophila</span> olfactory nervous system. The olfactory nervous system of <span class="html-italic">Drosophila</span> is involved in a series of neural processes. Odorants bind to olfactory receptors (ORs) on olfactory receptor neurons (ORNs) located in the sensilla of the antennae lobe (AL) and maxillary palps. The ORNs express specific odorant receptors that facilitate precise olfactory tuning. Subsequently, ORNs send their axons to the antennal lobe, where they form synaptic connections with projection neurons (PNs) in the glomeruli. Uniglomerular PNs transmit olfactory signals to two distinct brain regions in flies: the mushroom bodies (MB) and the lateral horn (LH). Ultimately, this information is relayed to the downstream brain regions through output neurons to influence behavior.</p>
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<p>Illustration of the various reward circuits identified in adult <span class="html-italic">Drosophila</span>. The identified circuits associated with behavioral responses to rewards encompassed (<b>A</b>) dopaminergic circuits; (<b>B</b>) the innervation of DANs (PAM) within the MB involved in synaptic connections related to reward across different MB compartments; (<b>C</b>) octopaminergic circuits; and (<b>D</b>) serotoninergic circuits. (MB: mushroom body; PAM: protocerebral anterior medial; FSB: fan-shaped body; EB: ellipsoid body; SEZ: subesophageal zone).</p>
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11 pages, 1073 KiB  
Article
Eutopic and Ectopic Endometrial Interleukin-17 and Interleukin-17 Receptor Expression at the Endometrial—Myometrial Interface in Women with Adenomyosis: Possible Pathophysiology Implications
by Le-Tien Hsu, Pei-Chen Lu, Yi-Wen Wang, Hsien-Ming Wu, I-Ju Chen and Hong-Yuan Huang
Int. J. Mol. Sci. 2024, 25(20), 11155; https://doi.org/10.3390/ijms252011155 - 17 Oct 2024
Abstract
Adenomyosis involves the infiltration of endometrial glands and stroma deep into the uterine tissue, causing disruption to the endometrial–myometrial interface (EMI). The role of interleukin-17 (IL-17) has been extensively studied in endometriosis, but its involvement in adenomyosis remains unclear. This study aimed to [...] Read more.
Adenomyosis involves the infiltration of endometrial glands and stroma deep into the uterine tissue, causing disruption to the endometrial–myometrial interface (EMI). The role of interleukin-17 (IL-17) has been extensively studied in endometriosis, but its involvement in adenomyosis remains unclear. This study aimed to investigate the expression of IL-17 in eutopic and ectopic endometrium (adenomyosis) of individuals with adenomyosis at the level of EMI. Paired tissues of eutopic endometrium and adenomyoma were collected from 16 premenopausal women undergoing hysterectomy due to adenomyosis. The IL-17 system was demonstrated in paired tissue samples at the level of EMI by the immunochemistry study. Gene expression levels of IL-17A and IL-17 receptor (IL-17R) were assessed through quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Comparative gene transcript amounts were calculated using the delta-delta Ct method. By immunohistochemical staining, CD4, IL-17A, and IL-17R proteins were detected in both eutopic endometrium and adenomyosis at the level of EMI. IL-17A and IL-17R were expressed mainly in the glandular cells, and the expression of both IL-17A and IL-17R was found to be stronger in adenomyosis than in endometrium. 3-Diaminobenzidine (DAB) staining revealed greater IL-17A expression in adenomyosis compared to eutopic endometrium. Quantitative RT-PCR showed 7.28-fold change of IL-17A and 1.99-fold change of IL-17R, and the fold change level of both IL-17A and IL-17R is significantly higher in adenomyosis (IL-17A: p = 0.047, IL-17R: p = 0.027) versus eutopic endometrium. We found significantly higher IL-17 levels in adenomyosis compared to eutopic endometrium at the level of EMI. The results showed that the IL-17 system may play a role in adenomyosis. Full article
(This article belongs to the Special Issue Endometriosis: From Molecular Basis to Therapy)
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<p>Immunohistochemistry of the IL-17 system in patients with adenomyosis. (<b>A</b>) Endometrial–myometrial interface stained by H&amp;E, and the circled area indicates the adenomyotic lesion. (<b>B</b>,<b>C</b>) Negative controls without staining: (<b>B</b>) endometrium and (<b>C</b>) adenomyosis. The brown stain indicated infiltration of CD4-positive immune cells in both glandular and stromal tissues of endometrium (<b>D</b>) and adenomyosis (<b>E</b>). The brown stain (red arrow) showed the IL-17A positive reaction mainly in the glandular cells of endometrium (<b>F</b>) and adenomyosis (<b>G</b>), and the dyeing is denser in adenomyosis (<b>G</b>) than in endometrium (<b>F</b>). The brown stain (red arrow) showed the IL-17R positive reaction mainly in the glandular cells of endometrium (<b>H</b>) and adenomyosis (<b>I</b>), and the dye is denser in adenomyosis (<b>I</b>) than in endometrium (<b>H</b>). (<b>A</b>) scale bar = 400 μm, (<b>B</b>,<b>C</b>) scale bar = 50 μm, (<b>D</b>–<b>I</b>) scale bar = 25 μm. H&amp;E: hematoxylin and eosin.</p>
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<p>Histogram. After the paired tissues are stained by DAB, 5 areas are randomly circled at both the eutopic endometrium and adenomyosis positions. In both paired tissues, the histograms show the density information for H&amp;E and DAB stain separately. DAB: 3,3-diaminobenzidine; H&amp;E: hematoxylin and eosin.</p>
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<p>Bar graph presentation of the fold change of IL-17A (<b>A</b>) and IL-17R (<b>B</b>) transcript quantified by real-time RT-PCR. Data presented are mean ± standard deviation. (<b>A</b>) IL-17A levels are significantly elevated in the adenomyosis group compared to the eutopic endometrium group (fold change = 7.28, <span class="html-italic">p</span> = 0.047). (<b>B</b>) IL-17R levels are significantly higher in the adenomyosis group compared to the eutopic endometrium group (fold change = 1.99, <span class="html-italic">p</span> = 0.027). * <span class="html-italic">p</span> &lt; 0.05. RT-PCR: reverse transcription polymerase chain reaction.</p>
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<p>Flow chart of study subjects.</p>
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15 pages, 5116 KiB  
Article
NPS-1034 Exerts Therapeutic Efficacy in Renal Cell Carcinoma Through Multiple Targets of MET, AXL, and TNFRSF1A Signaling in a Metastatic Model
by Ya-Chuan Chang, Chien-Te Liu, Chia-Ying Yu and Wen-Wei Sung
Cells 2024, 13(20), 1713; https://doi.org/10.3390/cells13201713 - 17 Oct 2024
Abstract
Renal cell carcinoma (RCC) has diverse pathological subtypes, most of which have a poor prognosis. Patients with advanced RCC require systemic therapies for disease control. Although targeted therapies and immune checkpoint inhibitors have shown therapeutic efficacy, patients eventually succumb to disease progression. Therefore, [...] Read more.
Renal cell carcinoma (RCC) has diverse pathological subtypes, most of which have a poor prognosis. Patients with advanced RCC require systemic therapies for disease control. Although targeted therapies and immune checkpoint inhibitors have shown therapeutic efficacy, patients eventually succumb to disease progression. Therefore, additional therapies targeting different pathways are needed to provide more therapeutic options for sequential treatment. Our study explored the biological mechanisms and therapeutic outcomes for NPS-1034, a dual MET/AXL inhibitor, in RCC, both in vivo and in vitro. Our results showed that NPS-1034 can significantly inhibit tumor proliferation and induce cancer cell apoptosis. Besides MET and AXL, known targets of NPS-1034, we identified TNFRSF1A as another target gene inhibited by NPS-1034 via antibody arrays. This was further supported by next-generation sequencing, showing that the TNF signaling pathway is one of the most significant NPS-1034-regulated pathways. Furthermore, one of the identified target genes, GADD45A, responsible for NPS-1034 anticancer properties, was significantly associated with patient survival in RCC. GADD45A expression was significantly upregulated via NPS-1034 and downregulated via TNFRSF1A overexpression. Finally, its therapeutic efficacy was demonstrated in vivo, showing that NPS-1034 significantly alleviated the tumor burden and inhibited cell proliferation in a lung metastatic animal model. In conclusion, we explored the therapeutic mechanism of NPS-1034 and found that it targets not only MET and AXL but also TNFRSF1A. In a lung metastatic animal model, we confirmed that NPS-1034 is a potential candidate for systemic therapy in RCC. Full article
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<p>NPS-1034 suppresses cell proliferation and induces apoptosis with the accumulation of a sub-G1-phase population of RCC cell lines. (<b>A</b>) An MTT assay was performed to analyze the cell viability of RCC cell lines A498, 786-0, and Caki-1 after NPS-1034 exposure for 24 h. (<b>B</b>) A colony formation assay was performed to analyze the RCC cell lines’ clonogenic ability after NPS-1034 exposure for 24 h. (<b>C</b>) A cell cycle analysis was performed after 48 h of treatment with NPS-1034 using a flow cytometer. The proportion of the cell cycle (<b>D</b>) and the cell percentage of the sub-G1 phase (<b>E</b>) are shown. (<b>F</b>) Flow cytometry results with Annexin V-FITC/PI staining. RCC cell lines were treated with NPS-1034 for 48 h, and (<b>G</b>) the proportions of Annexin V+/−/PI+/− cells are shown. (<b>H</b>) Fluorescence images were taken after Hoechst 33342 staining. Apoptosis-associated morphological changes are emphasized by white squares, and the (<b>I</b>) bar chart shows the percentage of apoptotic cells. Data are shown as mean ± S.D. (* <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>Gene ontology and KEGG enrichment analysis of NPS-1034-treated RCC cells. Biological processes enriched in relation to the (<b>A</b>,<b>C</b>,<b>E</b>) cell cycle or (<b>B</b>,<b>D</b>,<b>F</b>) apoptosis in RCC cells treated with 80 μM of NPS-1034 for 48 h. Terms in (<b>A</b>,<b>B</b>) the bar plot and (<b>E</b>,<b>F</b>) heatmap were ordered by <span class="html-italic">p</span>-value, while terms in the (<b>C</b>,<b>D</b>) dot plot were ordered by count number. (<b>G</b>) Dot plot and (<b>H</b>) bar plot of KEGG pathway enrichment analyses showing the identified statistically significantly enriched pathways under 80 μM of NPS-1034 for 48 h. (<b>I</b>) Heatmap analysis of the top 10 enriched pathways. Blue: upregulation; red: downregulation. (<b>J</b>) Heatmap analysis of the TNF signaling pathway revealing the clearest difference.</p>
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<p>NPS-1034 activates GADD45A, inhibits the MET and TNFRSF1A downstream signaling pathway proteins’ expression level, and upregulates the pro-apoptosis protein expression level in RCC cells. (<b>A</b>) Validation of NPS-1034, an MET/AXL inhibitor, on the MET downstream pathway protein expression level in RCC cells. (<b>B</b>) Assessment of the regulatory role of GADD45A and TNFR1-related pathways, such as the IκBα/NFκB signaling pathway. (<b>C</b>) The expression levels of several pro-apoptosis proteins were detected in RCC cells treated with NPS-1034 (0, 20, and 80 μM) for 48 h via Western blotting.</p>
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<p>The high expression of GADD45A correlates with a favorable prognosis and effect on the survival rate of patients with RCC. TNFRSF1A overexpression reversed the anticancer effects of NPS-1034 in RCC cells. (<b>A</b>) A volcano plot showing the differential expression of genes altered by NPS-1034 treatment in RCC cells. (<b>B</b>) Relative GADD45A mRNA expression in 877 patients. Kaplan–Meier plots showing the survival probabilities of RCC patients stratified by GADD45A expression. Patient survival details were derived from TCGA. (<b>C</b>) The increases in GADD45A-related pathway expression and the decreases in IκBα/NFκB-related pathway expression are all significantly reversed via TNFRSF1A overexpression.</p>
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<p>NPS-1034 alleviated the tumor burden and inhibited cell proliferation in a lung-metastatic animal model. (<b>A</b>) Flow chart and schematic overview of the Renca-luc metastatic animal model in vivo. (<b>B</b>) Representative image of gross lung specimens. The yellow arrow marks the site of tumor formation. (<b>C</b>) Mice lung weight normalized by body weight. Data are shown as mean ± S.D. (* <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) (<b>D</b>) Overview of pathological changes and the rate of cell proliferation in the tumor were analyzed by H&amp;E and Ki-67 staining. (<b>E</b>,<b>F</b>) Estimation of tumor burden by determining Ki-67-positive cells and mean intensity of all objects for Ki-67. Data are shown as mean ± S.D. (* <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>Schematic overview of NPS-1034-targeted pathways in RCC. Our results showed that NPS-1034 not only inhibits the known AXL and MET pathways but also inhibits the TNFRSF1A downstream signaling pathway and activates the GADD45A pathway. The favorable anticancer efficacy was also demonstrated in vivo in the Renca-luc metastatic animal model.</p>
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