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24 pages, 2507 KiB  
Article
A Novel Orchestrator Architecture for Deploying Virtualized Services in Next-Generation IoT Computing Ecosystems
by Francisco Mahedero Biot, Alejandro Fornes-Leal, Rafael Vaño, Raúl Reinosa Simón, Ignacio Lacalle, Carlos Guardiola and Carlos E. Palau
Sensors 2025, 25(3), 718; https://doi.org/10.3390/s25030718 - 24 Jan 2025
Viewed by 336
Abstract
The Next-Generation IoT integrates diverse technological enablers, allowing the creation of advanced systems with increasingly complex requirements and maximizing the use of available IoT–edge–cloud resources. This paper introduces an orchestrator architecture for dynamic IoT scenarios, inspired by ETSI NFV MANO and Cloud Native [...] Read more.
The Next-Generation IoT integrates diverse technological enablers, allowing the creation of advanced systems with increasingly complex requirements and maximizing the use of available IoT–edge–cloud resources. This paper introduces an orchestrator architecture for dynamic IoT scenarios, inspired by ETSI NFV MANO and Cloud Native principles, where distributed computing nodes often have unfixed and changing networking configurations. Unlike traditional approaches, this architecture also focuses on managing services across massively distributed mobile nodes, as demonstrated in the automotive use case presented. Apart from working as MANO framework, the proposed solution efficiently handles service lifecycle management in large fleets of vehicles without relying on public or static IP addresses for connectivity. Its modular, microservices-based approach ensures adaptability to emerging trends like Edge Native, WebAssembly and RISC-V, positioning it as a forward-looking innovation for IoT ecosystems. Full article
(This article belongs to the Special Issue Cloud and Edge Computing for IoT Applications)
15 pages, 5996 KiB  
Article
SNP rs9364554 Modulates Androgen Receptor Binding and Drug Response in Prostate Cancer
by Yuqian Yan, Lei Shi, Tao Ma, Liguo Wang and Haojie Huang
Biomolecules 2025, 15(1), 64; https://doi.org/10.3390/biom15010064 - 4 Jan 2025
Viewed by 669
Abstract
(1) Background: Prostate cancer treatment efficacy is significantly influenced by androgen receptor (AR) signaling pathways. SLC22A3, a membrane transporter, has been linked to SNP rs9364554 risk loci for drug efficacy in prostate cancer. (2) Methods: We examined the location of SNP rs9364554 in [...] Read more.
(1) Background: Prostate cancer treatment efficacy is significantly influenced by androgen receptor (AR) signaling pathways. SLC22A3, a membrane transporter, has been linked to SNP rs9364554 risk loci for drug efficacy in prostate cancer. (2) Methods: We examined the location of SNP rs9364554 in the genome and utilized TCGA and other publicly available datasets to analyze the association of this SNP with SLC22A3 transcription levels. We verified onco-mining findings in prostate cancer cell lines using quantitative PCR and Western blots. Additionally, we employed electrophoretic mobility shift assay (EMSA) to detect the binding affinity of transcription factors to this SNP. The ChIP-Seq was used to analyze the enrichment of H3K27ac on the SLC22A3 promoter. (3) Results: In this study, we revealed that SNP rs9364554 resides in the SLC22A3 gene and affects its transcription. The downregulation of SLC22A3 is associated with drug resistance. More importantly, we found that this SNP has different binding affinities with transcription factors, specifically FOXA1 and AR, which significantly affects their regulation of SLC22A3 transcription. (4) Conclusions: Our findings highlight the potential of using this SNP as a biomarker for predicting chemotherapeutic outcomes and uncover possible mechanisms underlying drug resistance in advanced prostate cancers. More importantly, it provides a clinical foundation for targeting FOXA1 to enhance drug efficacy in prostate cancer patients. Full article
(This article belongs to the Collection Feature Papers in Molecular Genetics)
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<p>The SLC22A3 expression is highly downregulated in prostate cancer tissues and negatively related to drug efficacy. (<b>A</b>,<b>B</b>) The SLC22A3 transcription level was compared between prostate normal and cancer tissues from the TCGA patient dataset [<a href="#B27-biomolecules-15-00064" class="html-bibr">27</a>] (<b>A</b>) and between paired prostate normal and cancer tissues from the TCGA patient dataset [<a href="#B27-biomolecules-15-00064" class="html-bibr">27</a>] (<b>B</b>). (<b>C</b>) The SLC22A3 transcription level was compared in patients between paired normal prostate tissues and cancer tissues from a previous study [<a href="#B29-biomolecules-15-00064" class="html-bibr">29</a>]. (<b>D</b>,<b>E</b>) The SLC22A3 transcription level was compared in patients among non-localized and metastatic prostate tissues from a previous study [<a href="#B30-biomolecules-15-00064" class="html-bibr">30</a>]. (<b>F</b>–<b>H</b>) The SLC22A3 was knocked out with two sgRNA constructs (#1 and #2) individually in C4-2 cells to detect the SLC22A3 protein level by Western blot analysis in (<b>F</b>), and drug treatment in (<b>G</b>,<b>H</b>). (<b>I</b>,<b>J</b>) Two sgSLC22A3 knockout cell lines (#1 and #2) were treated with JQ1 (2 µM) and Enzalutamide (2 µM) for clonogenic survival assay. The representative images are shown in (<b>I</b>) with quantification data in (<b>J</b>). Original images of (<b>F</b>) can be found in <a href="#app1-biomolecules-15-00064" class="html-app">supplementary Figure S3</a>. The following symbols were used to denote statistical significance: * <span class="html-italic">p</span> &lt; 0.05, *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>The heterozygous SNP rs9364554 promotes SLC22A3 expression. (<b>A</b>,<b>B</b>) The SLC22A3 transcription level was compared among different SNP rs9364554 genotypes in patients with normal prostate tissues (<b>A</b>) or prostate cancer tissues (<b>B</b>). (<b>C</b>) The SNP rs9364554 genotyping was performed with Sanger sequencing in six prostate cancer cell lines. (<b>D</b>,<b>E</b>) The cell line survey was conducted to detect SLC22A3 mRNA (<b>D</b>) and protein (<b>E</b>) levels. The red “*” indicates a potential FOXA1 mutant protein band. FL: full length. (<b>F</b>) A table summarizes genotypes of SNP rs9364554 of six prostate cancer cell lines and their molecular expression status of commonly expressed TFs. (<b>G</b>) UCSC tracks from published datasets [<a href="#B33-biomolecules-15-00064" class="html-bibr">33</a>] show patients’ profiles of ChIP-seq signals of AR in this SNP compared with two prostate cancer cell lines (C4-2 and LNCaP). Original images of (<b>E</b>) can be found in <a href="#app1-biomolecules-15-00064" class="html-app">supplementary Figure S3</a>. The following symbols were used to denote statistical significance: *** <span class="html-italic">p</span> &lt; 0.001. n.s., not significant.</p>
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<p>The SNP rs9364554 is manipulated by prostate cancer-specific TFs. (<b>A</b>) The online public datasets [<a href="#B33-biomolecules-15-00064" class="html-bibr">33</a>,<a href="#B36-biomolecules-15-00064" class="html-bibr">36</a>,<a href="#B37-biomolecules-15-00064" class="html-bibr">37</a>,<a href="#B38-biomolecules-15-00064" class="html-bibr">38</a>,<a href="#B39-biomolecules-15-00064" class="html-bibr">39</a>,<a href="#B40-biomolecules-15-00064" class="html-bibr">40</a>,<a href="#B41-biomolecules-15-00064" class="html-bibr">41</a>,<a href="#B42-biomolecules-15-00064" class="html-bibr">42</a>,<a href="#B43-biomolecules-15-00064" class="html-bibr">43</a>,<a href="#B44-biomolecules-15-00064" class="html-bibr">44</a>,<a href="#B45-biomolecules-15-00064" class="html-bibr">45</a>,<a href="#B46-biomolecules-15-00064" class="html-bibr">46</a>] reveal that SNP rs9364554 containing a DNA sequence is favorable by multiple prostate cancer-specific TFs (<b>A</b>). (<b>B</b>–<b>D</b>) The DNA sequence containing SNP rs9364554 (<b>B</b>) is overlapped with prostate cancer-specific TFs, such as FOXA1 (<b>C</b>) and AR (<b>D</b>). (<b>E</b>–<b>G</b>) The probe containing SNP rs9364554 (<b>E</b>) was designed to perform EMSA with 1 µg of nuclear protein extracts from four prostate cancer cell lines (PC-3, C4-2, VCaP and DU145) (<b>F</b>). The FOXA1 antibody was added to the reactions, which was followed by EMSA (<b>G</b>). The red “*” indicates a DNA/protein complex that might contain FOXA1 mutant protein. Original images of (<b>F,G</b>) can be found in <a href="#app1-biomolecules-15-00064" class="html-app">supplementary Figure S3</a>.</p>
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<p>The SLC22A3 transcription is negatively manipulated by FOXA1 while positively regulated by AR. (<b>A</b>) The transcription level of SLC22A3 was analyzed according to molecular signature from TCGA datasets with online software (accessed on 21 December 2021, <a href="https://ualcan.path.uab.edu/" target="_blank">https://ualcan.path.uab.edu/</a>). (<b>B</b>,<b>C</b>) The C4-2 cells were knocked down with the indicated TFs with siRNA, which was followed by qPCR to detect the mRNA level of SLC22A3 (<b>B</b>) and ChIP-qPCR to examine the enrichment of H3K27ac at the SLC22A3 promoter (<b>C</b>). (<b>D</b>) UCSC tracks from published datasets [<a href="#B48-biomolecules-15-00064" class="html-bibr">48</a>] show profiles of ChIP-seq signals of AR and H3K27ac in C4-2 cells. (<b>E</b>) UCSC tracks from published datasets [<a href="#B48-biomolecules-15-00064" class="html-bibr">48</a>] show profiles of RNA-seq signals of SLC22A3 after Enzalutamide treatment in C4-2 cells. The following symbols were used to denote statistical significance: n.s., not significant, * <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>The AR variants undermine SLC22A3 expression. (<b>A</b>) UCSC tracks from published datasets [<a href="#B47-biomolecules-15-00064" class="html-bibr">47</a>] show profiles of ChIP-seq signals of AR and H3K4me1 in AR FL and ARV-overexpressing cell lines. (<b>B</b>) VCaP nuclear protein extracts were incubated with biotin-labeled C allele, followed by the addition of 0.5 µg of AR or AR variant 7 antibody. The reactions were loaded to 6% of polyacrylamide DNA gel for EMSA assay. (<b>C</b>) The C4-2 cells were transfected with AR-FL or -V7 for 48 h and harvested for Western blot to detect the SLC22A3 protein level. Original images of (<b>B,C</b>) can be found in <a href="#app1-biomolecules-15-00064" class="html-app">supplementary Figure S3</a>.</p>
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<p>A working model to elucidate the interplay between FOXA1 and AR in regulating SLC22A3 transcription through SNP rs9364554. (<b>A</b>) Specifically, in primary prostate cancer, SLC22A3 is upregulated in AR FL-expressing cells but diminished in ARV-expressing cells in a background of C allele SNP rs9364554. However, in a background of T allele SNP rs9364554, FOXA1 competes AR in binding this site and undermines SLC22A3 transcription. (<b>B</b>) The mutations of FOXA1 enhance its binding affinity to either the C or T allele, resulting in the suppression of AR target gene expression. (<b>C</b>) In CRPC or NEPC patients, the lack of AR expression impairs SLC22A3 expression.</p>
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15 pages, 647 KiB  
Article
Anchor-Based Method for Inter-Domain Mobility Management in Software-Defined Networking
by Akichy Adon Jean Rodrigue Kanda, Amanvon Ferdinand Atta, Zacrada Françoise Odile Trey, Michel Babri and Ahmed Dooguy Kora
Algorithms 2024, 17(12), 566; https://doi.org/10.3390/a17120566 - 11 Dec 2024
Viewed by 568
Abstract
Recently, there has been an explosive growth in wireless devices capable of connecting to the Internet and utilizing various services anytime, anywhere, often while on the move. In the realm of the Internet, such devices are called mobile nodes. When these devices are [...] Read more.
Recently, there has been an explosive growth in wireless devices capable of connecting to the Internet and utilizing various services anytime, anywhere, often while on the move. In the realm of the Internet, such devices are called mobile nodes. When these devices are in motion or traverse different domains while communicating, effective mobility management becomes essential to ensure the continuity of their services. Software-defined networking (SDN), a new paradigm in networking, offers numerous possibilities for addressing the challenges of mobility management. By decoupling the control and data planes, SDN enables greater flexibility and adaptability, making them a powerful framework for solving mobility-related issues. However, communication can still be momentarily disrupted due to frequent changes in IP addresses, a drop in radio signals, or configuration issues associated with gateways. Therefore, this paper introduces Routage Inter-domains in SDN (RI-SDN), a novel anchor-based routing method designed for inter-domain mobility in SDN architectures. The method identifies a suitable anchor domain, a critical intermediary domain that contributes to reducing delays during data transfer because it is the closest domain (i.e., node) to the destination. Once the anchor domain is identified, the best routing path is determined as the route with the smallest metric, incorporating elements such as bandwidth, flow operations, and the number of domain hops. Simulation results demonstrate significant improvements in data transfer delay and handover latency compared to existing methods. By leveraging SDN’s potential, RI-SDN presents a robust and innovative solution for real-world scenarios requiring reliable mobility management. Full article
(This article belongs to the Section Algorithms for Multidisciplinary Applications)
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<p>Algorithm for anchor domain selection.</p>
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<p>Algorithm for route selection.</p>
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<p>Basic architecture, from [<a href="#B19-algorithms-17-00566" class="html-bibr">19</a>].</p>
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<p>Basic simplified architecture.</p>
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<p>Adjacency matrix.</p>
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<p>Architecture with routes.</p>
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<p>Architecture 2 × 3.</p>
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<p>Architecture 3 × 3.</p>
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<p>Architecture 3 × 4.</p>
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<p>Architecture 3 × 5.</p>
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<p>Data transfer delay.</p>
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<p>Handover latency.</p>
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15 pages, 772 KiB  
Article
Use of Mobile Phones and Radiofrequency-Emitting Devices in the COSMOS-France Cohort
by Isabelle Deltour, Florence Guida, Céline Ribet, Marie Zins, Marcel Goldberg and Joachim Schüz
Int. J. Environ. Res. Public Health 2024, 21(11), 1514; https://doi.org/10.3390/ijerph21111514 - 14 Nov 2024
Viewed by 1031
Abstract
COSMOS-France is the French part of the COSMOS project, an international prospective cohort study that investigates whether the use of mobile phones and other wireless technologies is associated with health effects and symptoms (cancers, cardiovascular diseases, neurologic pathologies, tinnitus, headaches, or sleep and [...] Read more.
COSMOS-France is the French part of the COSMOS project, an international prospective cohort study that investigates whether the use of mobile phones and other wireless technologies is associated with health effects and symptoms (cancers, cardiovascular diseases, neurologic pathologies, tinnitus, headaches, or sleep and mood disturbances). Here, we provide the first descriptive results of COSMOS-France, a cohort nested in the general population-based cohort of adults named Constances. Methods: A total of 39,284 Constances volunteers were invited to participate in the COSMOS-France study during the pilot (2017) and main recruitment phase (2019). Participants were asked to complete detailed questionnaires on their mobile phone use, health conditions, and personal characteristics. We examined the association between mobile phone use, including usage for calls and Voice over Internet Protocol (VoIP), cordless phone use, and Wi-Fi usage with age, sex, education, smoking status, body mass index (BMI), and handedness. Results: The participation rate was 48.4%, resulting in 18,502 questionnaires in the analyzed dataset. Mobile phone use was reported by 96.1% (N = 17,782). Users reported typically calling 5–29 min per week (37.1%, N = 6600), making one to four calls per day (52.9%, N = 9408), using one phone (83.9%, N = 14,921) and not sharing it (80.4% N = 14,295), mostly using the phone on the side of the head of their dominant hand (59.1%, N = 10,300), not using loudspeakers or hands-free kits, and not using VoIP (84.9% N = 15,088). Individuals’ age and sex modified this picture, sometimes markedly. Education and smoking status were associated with ever use and call duration, but neither BMI nor handedness was. Cordless phone use was reported by 66.0% of the population, and Wi-Fi use was reported by 88.4%. Conclusion: In this cross-sectional presentation of contemporary mobile phone usage in France, age and sex were important determinants of use patterns. Full article
(This article belongs to the Special Issue Epidemiology of Lifestyle-Related Diseases)
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<p>Flow chart for participation in the COSMOS-France study. Note: * excluded from the calculation of the participation rate.</p>
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<p>Description of laterality of mobile phone use among left-handed, ambidextrous, and right-handed participants of Cosmos-France, 2017–19. Percentages are shown excluding missing values, presented in white font.</p>
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22 pages, 5113 KiB  
Article
GDnet-IP: Grouped Dropout-Based Convolutional Neural Network for Insect Pest Recognition
by Dongcheng Li, Yongqi Xu, Zheming Yuan and Zhijun Dai
Agriculture 2024, 14(11), 1915; https://doi.org/10.3390/agriculture14111915 - 29 Oct 2024
Viewed by 799
Abstract
Lightweight convolutional neural network (CNN) models have proven effective in recognizing common pest species, yet challenges remain in enhancing their nonlinear learning capacity and reducing overfitting. This study introduces a grouped dropout strategy and modifies the CNN architecture to improve the accuracy of [...] Read more.
Lightweight convolutional neural network (CNN) models have proven effective in recognizing common pest species, yet challenges remain in enhancing their nonlinear learning capacity and reducing overfitting. This study introduces a grouped dropout strategy and modifies the CNN architecture to improve the accuracy of multi-class insect recognition. Specifically, we optimized the base model by selecting appropriate optimizers, fine-tuning the dropout probability, and adjusting the learning rate decay strategy. Additionally, we replaced ReLU with PReLU and added BatchNorm layers after each Inception layer, enhancing the model’s nonlinear expression and training stability. Leveraging the Inception module’s branching structure and the adaptive grouping properties of the WeDIV clustering algorithm, we developed two grouped dropout models, the iGDnet-IP and GDnet-IP. Experimental results on a dataset containing 20 insect species (15 pests and five beneficial insects) demonstrated an increase in cross-validation accuracy from 84.68% to 92.12%, with notable improvements in the recognition rates for difficult-to-classify species, such as Parnara guttatus Bremer and Grey (PGBG) and Papilio xuthus Linnaeus (PXLL), increasing from 38% and 47% to 62% and 93%, respectively. Furthermore, these models showed significant accuracy advantages over standard dropout methods on test sets, with faster training times compared to four conventional CNN models, highlighting their suitability for mobile applications. Theoretical analyses of model gradients and Fisher information provide further insight into the grouped dropout strategy’s role in improving CNN interpretability for insect recognition tasks. Full article
(This article belongs to the Section Digital Agriculture)
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<p>Architecture of GDnet-IP. (<b>A</b>) BatchNorm modules (BN) and clustering-based grouped dropout are introduced into the initial CPAFNet model; (<b>B</b>) Inception-based grouped dropout, in which one of the branches (grey branch) is randomly deactivated; (<b>C</b>) Clustering-based grouped dropout, in which the channels in ‘Group 2’ are randomly deactivated.</p>
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<p>Optimization path of hyper-parameters for the CPAFnet baseline model. The classification accuracy (BA) colored in green represents optiCPAFnet-1 with an Adam optimizer and a classic dropout rate of 0.5. The BA in blue represents optiCPAFnet-2 (considered a reliable reproduction of the CPAFnet model) with an optimized learning rate of 0.0008 and a decay constraint. The BA in red represents optiCPAFnet-3 with the PreLU activation function and the inclusion of BatchNorm modules.</p>
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<p>Comparison of the model’s loss function changes before and after adding the learning rate decay. The subgraph in the upper-right-hand corner is a zoomed-in view after 700 training iterations; the red curve represents no learning rate decay, while the blue curve represents learning rate with decay.</p>
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<p>Frequency distribution of the clusters obtained from feature channels. Clustering was performed on the output of the global pooling layer using WeDIV every 50 training iterations.</p>
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<p>Confusion matrices for insect identification on independent Test Set 1 for different models. (<b>A</b>) Confusion matrix for the optiCPAFnet-2 model; (<b>B</b>) Confusion matrix for the optiCPAFnet-3 model; (<b>C</b>) Confusion matrix for the GDnet-IP model.</p>
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<p>Confusion matrices for insect identification on independent Test Set 1 for different models. (<b>A</b>) Confusion matrix for the optiCPAFnet-2 model; (<b>B</b>) Confusion matrix for the optiCPAFnet-3 model; (<b>C</b>) Confusion matrix for the GDnet-IP model.</p>
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<p>Grad-CAM heatmap of PXLL: (<b>A</b>) Grad-CAM heatmap of PXLL in the OptiCPAFnet-2 model, (<b>B</b>) Grad-CAM heatmap of PXLL in the OptiCPAFnet-3 model, (<b>C</b>) Grad-CAM heatmap of PXLL in the GDnet-IP model.</p>
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<p>Comparison of insect classification models based on different dropout methods. Letters on the boxplot were derived from one-way ANOVA. Cross-validation accuracy was obtained from samples excluding test set images. Test Set 1 includes original and augmented images, while Test Set 2 consists of original images only. The two reference dropout methods were based on the optiCPAFnet-3 model. iGDnet-IP is a CNN model involving Inception module-based grouped dropout, and Gdnet-IP is a model adopting clustering-based grouped dropout.</p>
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<p>Comparison of insect classification accuracy between GDnet-IP and classic CNN models. The lowercase letters shown above the bars indicate the marks of statistical significance differences. (<b>A</b>) Cross-validation accuracy of each model; (<b>B</b>) Prediction performance of each model on Test Set 1 (with image augmentation) and Test Set 2 (without image augmentation); (<b>C</b>) Training time of each model (in seconds).</p>
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<p>Comparison of insect classification accuracy between GDnet-IP and classic CNN models. The lowercase letters shown above the bars indicate the marks of statistical significance differences. (<b>A</b>) Cross-validation accuracy of each model; (<b>B</b>) Prediction performance of each model on Test Set 1 (with image augmentation) and Test Set 2 (without image augmentation); (<b>C</b>) Training time of each model (in seconds).</p>
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<p>Parameter and gradient changes during the training iterations for two models. (<b>A</b>) Changes in the amplitude of model parameter update; (<b>B</b>) Changes in the model gradient norm calculated every 10 iterations; (<b>C</b>) Changes in the model gradient variance.</p>
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<p>FIM scores and classification accuracy on Test Set 1 during the training iterations for two models.</p>
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42 pages, 1312 KiB  
Article
Mobility–Multihoming Duality
by Ryo Yanagida and Saleem Noel Bhatti
Future Internet 2024, 16(10), 358; https://doi.org/10.3390/fi16100358 - 1 Oct 2024
Viewed by 957
Abstract
In modern Internet-based communication, especially mobile systems, a mobile node (MN) will commonly have more than one possibility for Internet Protocol (IP) connectivity. For example, an MN such as a smartphone may be associated with an IEEE 802.11 network at a site while [...] Read more.
In modern Internet-based communication, especially mobile systems, a mobile node (MN) will commonly have more than one possibility for Internet Protocol (IP) connectivity. For example, an MN such as a smartphone may be associated with an IEEE 802.11 network at a site while also connected to a cellular base station for 5G. In such a scenario, the smartphone might only be able to utilise the IEEE 802.11 network, not making use of the cellular connectivity simultaneously. Currently, IP does not allow applications and devices to easily utilise multiple IP connectivity opportunities—multihoming for the MN—without implementing special mechanisms to manage them. We demonstrate how the use of the Identifier Locator Network Protocol (ILNP), realised as an extension to IPv6, can enable mobility with multihoming using a duality mechanism that treats mobility and multihoming as the same logical concept. We present a network layer solution that does not require any modification to transport protocols, can be implemented using existing application programming interfaces (APIs), and can work for any application. We have evaluated our approach using an implementation in Linux and a testbed. The testbed consisted of commercial equipment to demonstrate that our approach can be used over existing network infrastructure requiring only normal unicast routing for IPv6. Full article
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<p>Comparison of the IPv6 unicast address format with the ILNP unicast addressing format. The L64 value has the same syntax and semantics as the IPv6 routing prefix. The NID value has the same syntax as the IPv6 Interface Identifier, but it has different semantics. The NID-L64 pairing is an Identifier Locator Vector (IL-V), which can be used the same way as an IPv6 address.</p>
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<p>An example of a Locator Update (LU) handshake for a Mobile Node (MN). The MN discovers a new L64 value via an IPv6 Router Advertisement (RA) message. It updates its local ILNP Communication Cache (ILCC) and sends an LU message to the Correspondent Node (CN). The CN updates its own ILCC and sends a LU-ack (acknowledgement) to the MN.</p>
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<p>The ILNP IPv6 extension header as in RFC6744.</p>
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<p>The ILNP LU message structure based on the message format from RFC6743.</p>
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<p>A flowchart describing UDP/TCP packet processing with ILNP mobility–multihoming duality mechanism with Deficit Round-Robin (DRR) load sharing. Overall, the existing IPv6 packet processing code path has been re-used and modified effectively. Grey boxes indicate unmodified processes with respect to IPv6 packet processing. Orange boxes indicate modifications of existing IPv6 packet processing logic. Green boxes are the additional logic and processing for ILNP.</p>
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<p>A scenario diagram describing host movement for the mobility–multihoming duality evaluation. There are four IPv6 networks, aa–dd, connected via the 4 routers, R1–R4, scenario. Network dd is used connect R1, R2, and R3 to R4, and it represents connectivity on over the Internet between MN and CN. The arrow labelled 1 is the first movement the MN carries out: moving from network aa on R1 to network cc on R3. The arrow labelled 2 shows the second set of movement, where the MN returns from network cc back to network aa.</p>
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<p>A timeline diagram showing an example of a mobility–multihoming duality scenario. The MN has three interfaces, and the CN has one interface. The MN starts communication only on network aa. The MN and the CN begin a communication session using a single interface on both sides. The MN activates interface 2, receives L64 (IPv6 prefix) <tt>bb</tt>, sends an LU, and sets the new L64 as ACTIVE. The CN responds with an LU-Ack, acknowledging the new set of L64 values that the MN now has. The MN continues to activate another interface, which is also signalled to the CN. The MN then lists the first interface in the <tt>net.ilnp6.disabled_interface</tt> <tt>sysctl</tt> list, triggering another LU and state changes in the ILCC. After the CN acknowledges the removal of the first interface, the MN removes the interface.</p>
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<p>The procedure for a data collection run. Both CN and MN initially have only a single interface (i/f) enabled. <tt>iperf2</tt> is started with bi-directional data transfer. Additional interfaces are enabled at the MN until all interfaces are enabled. Then, interfaces are disabled at the MN until only a single interface remains enabled. This is repeated so that all additional interfaces have been enabled/disabled twice.</p>
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<p>Plots showing packet delivery statistics of TCP and UDP over ILNP. Note that the y axis is in the range of 0.00–0.01, i.e., 0.00–1.00%. The box around the median value is invisible, as the results were consistent across the runs, and the rate remained near zero. In all cases, both the misorder and loss were very low and very consistent across multiple runs. Note that the different transmission characteristics and behaviours for TCP and UDP mean these metrics are not directly comparable. (<b>a</b>) TCP misordering ratio based on sequence numbers (data packets) and acknowledgement numbers received. Negligible misordering was observed. (<b>b</b>) TCP duplicate ratio based on sequence numbers (data packets) and acknowledgement numbers sent and received.No significant numbers of duplicate packets were observed in the sequence numbers or the acknowledgement numbers. (<b>c</b>) UDP packet statistics observed in mobility–multihoming duality scenarios with <tt>iperf2</tt> UDP over ILNP. With all scenarios, both misordering and loss ratio remained low or nil. The small size of the box indicates that there was little to no variation across different runs.</p>
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<p>Plots showing the throughput for TCP and UDP over ILNP. Note that, due to the different protocols and their characteristics, these are not directly comparable to each other. (<b>a</b>) Throughput observed in the mobility–multihoming duality scenarios with <tt>iperf2</tt> TCP flows over ILNP. Across all delay scenarios, the throughput remained near the 10 Mbps target with little variation, as shown by barely visible 25th and 75th percentile line of the box plot. Note that the <span class="html-italic">y</span> axis is in the range of 9.0–11.0 Mbps. The box around the median value is invisible, as the results were consistent across the runs, and the value remained near 10.2 Mbps. (<b>b</b>) Throughput observed in mobility–multihoming duality scenarios with <tt>iperf2</tt> UDP flows over ILNP. The throughput remained consistent at around the 10 Mbps target with very few exceptions. Note that the <span class="html-italic">y</span> axis is in the range of 9.0–11.0 Mbps. The box around the median value is invisible, as the results were consistent across the runs, and the value remained near 10.1 Mbps.</p>
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<p>Plots showing the throughput and sequence numbers observed in typical mobility–multihoming duality <tt>iperf2</tt> TCP scenario evaluations received at the CN. In each column, the top graph is throughput (faceted top to bottom as network aa, bb, cc, and aggregate). There was consistent aggregate throughput (bottom facet), with the expected throughput observed at the respective source/destination IL-V on each network (aa, bb, cc) as expected. The vertical dashed line shows the Locator Update (LU) message event. In each column, the lower graph is the TCP sequence number progression. This also showed consistent increase, indicating a consistent flow and delivery of packets.</p>
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<p>Plots showing the throughput and sequence numbers observed in typical mobility–multihoming duality <tt>iperf2</tt> TCP scenario evaluations received at the MN. In each column, the top graph is throughput (faceted top to bottom as network aa, bb, cc, and aggregate). There was consistent aggregate throughput (bottom facet), with the expected throughput observed at the respective source/destination IL-V on each network (aa, bb, cc) as expected. The vertical dashed line shows the Locator Update (LU) message event. In each column, the lower graph is the TCP sequence number progression. This also showed consistent increase, indicating a consistent flow and delivery of packets.</p>
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<p>Plots showing the throughput and sequence numbers observed in typical mobility–multihoming duality <tt>iperf2</tt> UDP scenario evaluations received at the CN. In each column, the top graph is throughput (faceted top to bottom as network aa, bb, cc, and aggregate). There was consistent aggregate throughput (bottom facet), with the expected throughput observed at the respective source/destination IL-V on each network (aa, bb, cc) as expected. The vertical dashed line shows the Locator Update (LU) message event. In each column, the lower graph is the <tt>iperf2</tt> sequence number progression. This also showed consistent increase, indicating a consistent flow and delivery of packets.</p>
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<p>Plots showing the throughput and sequence numbers observed in typical mobility–multihoming duality <tt>iperf2</tt> UDP scenario evaluations received at the MN. In each column, the top graph is throughput (faceted top to bottom as network aa, bb, cc, and aggregate). There was consistent aggregate throughput (bottom facet), with the expected throughput observed at the respective source/destination IL-V on each network (aa, bb, cc) as expected. The vertical dashed line shows the Locator Update (LU) message event. In each column, the lower graph is the <tt>iperf2</tt> sequence number progression. This also showed consistent increase, indicating a consistent flow and delivery of packets.</p>
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<p>Box plot showing MP-TCP flow for 20 runs with no added delay on path. While the individual interfaces may exhibit ‘bursty’ behaviour due to the way multipath congestion control algorithm distributes traffic, it satisfies the target load requirement of 10 Mbps.</p>
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<p>MP-TCP typical behaviour on the same testbed as for the ILNP evaluation. The distribution of the throughput is uneven, and changes to throughput on the individual interfaces are ‘bursty’. The vertical line shows the protocol level signalling (MP-TCP-specific multipath control plane protocol) to add or remove connectivity received at the respective IPv6 addresses. (<b>a</b>) Throughput facet plot of MP-TCP flow received at the MN. The top three plots show the throughput received at the addresses of the respective three interfaces at the MN, and the bottom plot shows the aggregate throughput. (<b>b</b>) Throughput facet plot of MP-TCP flow received at the CN. The top three plots show the throughputs received from the addresses of the respective three interfaces at the MN, and the bottom plot shows the aggregate throughput.</p>
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<p>MP-TCP typical behaviour on the same testbed as for the ILNP evaluation. The distribution of the throughput is uneven, and changes to throughput on the individual interfaces are ‘bursty’. The vertical line shows the protocol level signalling (MP-TCP-specific multipath control plane protocol) to add or remove connectivity received at the respective IPv6 addresses. (<b>a</b>) Throughput facet plot of MP-TCP flow received at the MN. The top three plots show the throughput received at the addresses of the respective three interfaces at the MN, and the bottom plot shows the aggregate throughput. (<b>b</b>) Throughput facet plot of MP-TCP flow received at the CN. The top three plots show the throughputs received from the addresses of the respective three interfaces at the MN, and the bottom plot shows the aggregate throughput.</p>
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13 pages, 1475 KiB  
Article
Nongenetic and Genetic Factors Associated with White Matter Brain Aging: Exposome-Wide and Genome-Wide Association Study
by Li Feng, Halley S. Milleson, Zhenyao Ye, Travis Canida, Hongjie Ke, Menglu Liang, Si Gao, Shuo Chen, L. Elliot Hong, Peter Kochunov, David K. Y. Lei and Tianzhou Ma
Genes 2024, 15(10), 1285; https://doi.org/10.3390/genes15101285 - 30 Sep 2024
Viewed by 1583
Abstract
Background/Objectives: Human brain aging is a complex process that affects various aspects of brain function and structure, increasing susceptibility to neurological and psychiatric disorders. A number of nongenetic (e.g., environmental and lifestyle) and genetic risk factors are found to contribute to the varying [...] Read more.
Background/Objectives: Human brain aging is a complex process that affects various aspects of brain function and structure, increasing susceptibility to neurological and psychiatric disorders. A number of nongenetic (e.g., environmental and lifestyle) and genetic risk factors are found to contribute to the varying rates at which the brain ages among individuals. Methods: In this paper, we conducted both an exposome-wide association study (XWAS) and a genome-wide association study (GWAS) on white matter brain aging in the UK Biobank, revealing the multifactorial nature of brain aging. We applied a machine learning algorithm and leveraged fractional anisotropy tract measurements from diffusion tensor imaging data to predict the white matter brain age gap (BAG) and treated it as the marker of brain aging. For XWAS, we included 107 variables encompassing five major categories of modifiable exposures that potentially impact brain aging and performed both univariate and multivariate analysis to select the final set of nongenetic risk factors. Results: We found current tobacco smoking, dietary habits including oily fish, beef, lamb, cereal, and coffee intake, length of mobile phone use, use of UV protection, and frequency of solarium/sunlamp use were associated with the BAG. In genetic analysis, we identified several SNPs on chromosome 3 mapped to genes IP6K1, GMNC, OSTN, and SLC25A20 significantly associated with the BAG, showing the high heritability and polygenic architecture of human brain aging. Conclusions: The critical nongenetic and genetic risk factors identified in our study provide insights into the causal relationship between white matter brain aging and neurodegenerative diseases. Full article
(This article belongs to the Special Issue Advances in Bioinformatics and Environmental Health)
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<p>Overview of the analytical steps in this study.</p>
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<p>Coefficients and 95% CIs of the 17 exposure variables selected in the univariate analysis of XWAS. Variables are ordered by categories. Dots represents coefficients, and lines represent the 95% CIs.</p>
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<p>Manhattan plot of association results from GWAS on BAGs. Chromosome numbers are shown on the <span class="html-italic">x</span>-axis, and −log10 association <span class="html-italic">p</span>-values on the <span class="html-italic">y</span>-axis.</p>
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29 pages, 9496 KiB  
Article
Trustworthy Communities for Critical Energy and Mobility Cyber-Physical Applications
by Juhani Latvakoski, Jouni Heikkinen, Jari Palosaari, Vesa Kyllönen and Jari Rehu
Smart Cities 2024, 7(5), 2616-2644; https://doi.org/10.3390/smartcities7050102 - 12 Sep 2024
Viewed by 1243
Abstract
The aim of this research has been to enable the management of trustworthy relationships between stakeholders, service providers, and physical assets, which are required in critical energy and mobility cyber–physical systems (CPS) applications. The achieved novel contribution is the concept of trustworthy communities [...] Read more.
The aim of this research has been to enable the management of trustworthy relationships between stakeholders, service providers, and physical assets, which are required in critical energy and mobility cyber–physical systems (CPS) applications. The achieved novel contribution is the concept of trustworthy communities with respective experimental solutions, which are developed by relying on verifiable credentials, smart contracts, trust over IP, and an Ethereum-based distributed ledger. The provided trustworthy community solutions are validated by executing them in two practical use cases, which are called energy flexibility and hunting safety. The energy flexibility case validation considered the execution of the solutions with one simulated and two real buildings with the energy flexibility aggregation platform, which was able to trade the flexibilities in an energy flexibility marketplace. The provided solutions were executed with a hunting safety smartphone application for a hunter and the smartwatch of a person moving around in the forest. The evaluations indicate that conceptual solutions for trustworthy communities fulfill the purpose and contribute toward making energy flexibility trading and hunting safety possible and trustworthy enough for participants. A trustworthy community solution is required to make value sharing and usage of critical energy resources and their flexibilities feasible and secure enough for their owners as part of the energy flexibility community. Sharing the presence and location in mobile conditions requires a trustworthy community solution because of security and privacy reasons, but it can also save lives in real-life elk hunting cases. During the evaluations, the need for further studies related to performance, scalability, community applications, verifiable credentials with wallets, sharing of values and incentives, authorized trust networks, dynamic trust situations, time-sensitive behavior, autonomous operations with smart contracts through security assessment, and applicability have been detected. Full article
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<p>A view to the context of the challenges and the research question—How do we take care of the required trustworthy relationships and communities between stakeholders when monitoring, controlling, and using devices, and when do we use exposed data in a smart way? Solid violet lines in the figure represent device management carried by companies, dashed lines represent relationships requiring some kind of contracts, e.g., between companies (dashed green lines), between people and companies (dashed red lines), between people or organizations (dashed blue lines).</p>
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<p>A view to the requirements of the energy flexibility case.</p>
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<p>A view to the requirements for mobile services in the hunting safety case.</p>
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<p>The conceptual model of trustworthy communities.</p>
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<p>Examples of communities, resources, and related relationships.</p>
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<p>An example hierarchy of identities.</p>
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<p>The trust triangle. When the verifier trusts the Issuer (dashed line), trust can be established with the Holder (solid line) [<a href="#B2-smartcities-07-00102" class="html-bibr">2</a>,<a href="#B3-smartcities-07-00102" class="html-bibr">3</a>].</p>
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<p>Control data for security to establish a secure end-to-end data flow among physical entities.</p>
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<p>An example view of a verifiable data registry with application of Ethereum type of smart contracts.</p>
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<p>Structure of the experimental solutions (CPSHub@vtt) for the trustworthy communities.</p>
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<p>An example view of trust and community services is represented here by the CPSHub user interface.</p>
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<p>An example view of the smart contract application user interface.</p>
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<p>A view to the messaging services of CPSHub.</p>
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<p>An example view of CPSHub dashboard.</p>
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<p>A view to the setup of the energy flexibility case for testing experimental solutions for trustworthy communities.</p>
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<p>A view of the users, communities, roles, topics, devices, contracts, and data-sharing relationships applied in the energy flexibility case.</p>
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<p>A view to the setup of the hunting safety case for testing experimental solutions for trustworthy communities.</p>
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<p>A view of the users, communities, roles, topics, devices, contracts, and data-sharing relationships applied in the hunting safety case.</p>
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18 pages, 2732 KiB  
Article
Increased Myocardial MAO-A, Atrogin-1, and IL-1β Expression in Transgenic Mice with Pancreatic Carcinoma—Benefit of MAO-A Inhibition for Cardiac Cachexia
by Kira Stelter, Annalena Alabssi, Gabriel Alejandro Bonaterra, Hans Schwarzbach, Volker Fendrich, Emily P. Slater, Ralf Kinscherf and Wulf Hildebrandt
Biomedicines 2024, 12(9), 2009; https://doi.org/10.3390/biomedicines12092009 - 3 Sep 2024
Viewed by 1018
Abstract
Cancer cachexia (CC) continues to challenge clinicians by massively impairing patients’ prognosis, mobility, and quality of life through skeletal muscle wasting. CC also includes cardiac cachexia as characterized by atrophy, compromised metabolism, innervation and function of the myocardium through factors awaiting clarification for [...] Read more.
Cancer cachexia (CC) continues to challenge clinicians by massively impairing patients’ prognosis, mobility, and quality of life through skeletal muscle wasting. CC also includes cardiac cachexia as characterized by atrophy, compromised metabolism, innervation and function of the myocardium through factors awaiting clarification for therapeutic targeting. Because monoamine oxidase-A (MAO-A) is a myocardial source of H2O2 and implicated in myofibrillar protein catabolism and heart failure, we presently studied myocardial MAO-A expression, inflammatory cells, and capillarization together with transcripts of pro-inflammatory, -angiogenic, -apoptotic, and -proteolytic signals (by qRT-PCR) in a 3x-transgenic (LSL-KrasG12D/+; LSL-TrP53R172H/+; Pdx1-Cre) mouse model of orthotopic pancreatic ductal adenoarcinoma (PDAC) compared to wild-type (WT) mice. Moreover, we evaluated the effect of MAO-A inhibition by application of harmine hydrochloride (HH, 8 weeks, i.p., no sham control) on PDAC-related myocardial alterations. Myocardial MAO-A protein content was significantly increased (1.69-fold) in PDAC compared to WT mice. PDAC was associated with an increased percentage of atrogin-1+ (p < 0.001), IL-1β+ (p < 0.01), COX2+ (p < 0.001), and CD68+ (p > 0.05) cells and enhanced transcripts of pro-inflammatory IL-1β (2.47-fold), COX2 (1.53-fold), TNF (1.87-fold), and SOCS3 (1.64-fold). Moreover, PDAC was associated with a reduction in capillary density (−17%, p < 0.05) and transcripts of KDR (0.46-fold) but not of VEGFA, Notch1, or Notch3. Importantly, HH treatment largely reversed the PDAC-related increases in atrogin-1+, IL-1β+, and TNF+ cell fraction as well as in COX2, IL-1β, TNF, and SOCS3 transcripts, whereas capillary density and KDR transcripts failed to improve. In mice with PDAC, increased myocardial pro-atrophic/-inflammatory signals are attributable to increased expression of MAO-A, because they are significantly improved with MAO-A inhibition as a potential novel therapeutic option. The PDAC-related loss in myocardial capillary density may be due to other mechanisms awaiting evaluation with consideration of cardiomyocyte size, cardiac function and physical activity. Full article
(This article belongs to the Collection Feature Papers in Cell Biology and Pathology)
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<p>Relative MAO-A protein content in the ventricular left myocardium of untreated or HH-treated wild type (WT, WT-HH) and PDAC-bearing mice (CA, CA-HH). Data are given as mean ± SEM. Two-factorial ANOVA detected a significant increasing effect of factor CA (<span class="html-italic">p</span> = 0.02) but no impact of factor HH (<span class="html-italic">p</span> = 0.61) on MAO-A content; (<span class="html-italic">n</span> = 4 independent experiments); * for <span class="html-italic">p</span> &lt; 0.05 CA + CA-HH vs. WT + WT-HH. Representative Western blots for MAO-A and for tubulin (loading control) are given below with indications of the sample group assignments.</p>
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<p>Atrogin-1+ cells in the ventricular left myocardium of WT (<span class="html-italic">n</span> = 7), WT-HH (<span class="html-italic">n</span> = 11), CA (<span class="html-italic">n</span> = 7), and CA-HH (<span class="html-italic">n</span> = 9) mice. (<b>a</b>) Percentage of atrogin-1+ cells. Data are given as mean ± SEM. Two-factorial ANOVA detected a significant opposing impact of factor CA (<span class="html-italic">p</span> &lt; 0.001) and factor HH treatment (<span class="html-italic">p</span> &lt; 0.05), with significant interaction (<span class="html-italic">p</span> &lt; 0.01) within the total study population. ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 CA vs. WT or CA-HH vs. WT-HH; ## <span class="html-italic">p</span> &lt; 0.01, WT-HH vs. WT or CA-HH vs. CA; ++ <span class="html-italic">p</span> &lt; 0.01 CA-HH vs. WT. (<b>b</b>) Representative photos of left myocardial cross-sections of WT, WT-HH, CA, and CA-HH mice indicating five examples of atrogin-1+ (black arrows) and atrogin-1-negative cardiomyocytes (empty arrow heads).</p>
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<p>ILβ+ cells in the left ventricular myocardium of WT, WT-HH, CA, and CA-HH mice. (<b>a</b>) Percentage of IL-1β+ cells. Data are given as mean ± SEM. Two-factorial ANOVA detected significant opposing impacts of factor CA (<span class="html-italic">p</span> &lt; 0.001) and factor HH treatment (<span class="html-italic">p</span> &lt; 0.001) without significant interaction within the total study population. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 CA vs. WT or CA-HH vs. WT-HH; ## <span class="html-italic">p</span> &lt; 0.01, WT-HH vs. WT or CA-HH vs. CA. (<b>b</b>) Representative photos of left myocardial cross-sections of WT, WT-HH, CA, and CA-HH mice showing IL-1β+ cells (arrows). (<b>c</b>) x-fold expression of IL-1β transcripts in the left myocardium of WT-HH, CA, and CA-HH mice relative to WT mice as assessed in pooled samples.</p>
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<p>TNF+ cells in the ventricular left myocardium of WT, WT-HH, CA, and CA-HH mice. (<b>a</b>) Percentage TNF+ cells. Data are given as mean ± SEM. Two-factorial ANOVA applied to the total study population detected no significant impact of factor CA or factor HH treatment; however, revealed a significant interaction (<span class="html-italic">p</span> &lt; 0.05) between these factors, as reflected by a significant decrease in increased TNF+ cell density through HH in PDAC-bearing mice. # <span class="html-italic">p</span> &lt; 0.05 (posthoc) CA-HH vs. CA. (<b>b</b>) Representative photos of left myocardial cross-sections of WT, WT-HH, CA, and CA-HH mice showing TNF+ cells (arrows). (<b>c</b>) x-fold expression of TNF transcripts in the left myocardium of WT-HH, CA, and CA-HH relative to WT mice as assessed in pooled samples.</p>
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<p>CD68+ cells in the left ventricular myocardium of WT, WT-HH, CA, and CA-HH mice. (<b>a</b>) Percentage CD68+ cells. Data are given as mean ± SEM. Two-factorial ANOVA detected no significant impact of factor CA or factor HH treatment; however, revealed a significant interaction (<span class="html-italic">p</span> ≤ 0.05) between these factors within the total study population. * <span class="html-italic">p</span> &lt; 0.05 CA vs. WT. # <span class="html-italic">p</span> &lt; 0.05 WT-HH vs. WT. (<b>b</b>) Representative photos of left myocardial cross-sections of WT, WT-HH, CA, and CA-HH mice showing CD68+ cells (arrows). (<b>c</b>) X-fold expression of CD68 transcripts in WT-HH, CA, and CA-HH relative to WT mice as assessed in pooled samples.</p>
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<p>COX2+ cells in the left ventricular myocardium of WT, WT-HH, CA, and CA-HH mice. (<b>a</b>) Percentage of COX2+ cells. Data are given as mean ± SEM. Two-factorial ANOVA detected significant impacts of factor CA (<span class="html-italic">p</span> &lt; 0.001) and factor HH treatment (<span class="html-italic">p</span> &lt; 0.001) with significant interaction (<span class="html-italic">p</span> &lt; 0.05) within the total study population. * <span class="html-italic">p</span> &lt; 0.05, *** <span class="html-italic">p</span> &lt; 0.001 CA vs. WT or CA-HH vs. WT-HH; ### <span class="html-italic">p</span> &lt; 0.001 WT-HH vs. WT or CA-HH vs. CA. +++ <span class="html-italic">p</span> &lt; 0.001 CA-HH vs. WT. (<b>b</b>) Representative photos of left myocardial cross-sections of WT, WT-HH, CA, and CA-HH mice showing COX2+ cells (arrows). (<b>c</b>) X-fold expression of COX2 transcripts in the left myocardium of WT-HH, CA, and CA-HH mice relative to WT mice as assessed in pooled samples.</p>
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<p>Capillary density in the ventricular left myocardium of WT, WT-HH, CA, and CA-HH mice. (<b>a</b>) Density of capillaries (n/mm<sup>2</sup>, diameter ≤ 7 µm, stained for α-lectin). Data are given as mean ± SEM. Two-factorial ANOVA detected a significant impact of factor PDAC (<span class="html-italic">p</span> &lt; 0.001). but not factor HH. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 CA vs. WT or CA-HH vs. WT-HH. (<b>b</b>) Representative photos of left myocardial cross-sections of WT, WT-HH, CA, and CA-HH mice showing α-lectin+ capillaries. (<b>c</b>) X-fold expression of KDR transcripts in the left myocardium of WT-HH, CA, and CA-HH relative to WT mice as assessed in pooled samples.</p>
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16 pages, 4582 KiB  
Article
Strategies to Increase the Phosphorus Content in the Soil Profile of Vineyards Grown in Subtropical Climates
by Adriele Tassinari, Lincon Stefanello, Jean Michel Moura-Bueno, Gustavo Nogara de Siqueira, Guilherme Zanon Peripolli, Bianca Goularte Dias, Douglas Luiz Grando, William Natale, Carlos Alberto Ceretta and Gustavo Brunetto
Plants 2024, 13(17), 2434; https://doi.org/10.3390/plants13172434 - 31 Aug 2024
Cited by 1 | Viewed by 897
Abstract
Phosphate fertilizers are applied to the soil surface, especially in vineyards in production in subtropical regions. Nowadays, phosphorus (P) is not incorporated into the soil to avoid mechanical damage to the root system in orchards. However, over the years, successive surface P applications [...] Read more.
Phosphate fertilizers are applied to the soil surface, especially in vineyards in production in subtropical regions. Nowadays, phosphorus (P) is not incorporated into the soil to avoid mechanical damage to the root system in orchards. However, over the years, successive surface P applications can increase the P content only in the topsoil, maintaining low P levels in the subsurface, which can reduce its use by grapevines. For this reason, there is a need to propose strategies to increase the P content in the soil profile of established orchards. The study aimed to evaluate the effect of management strategies to (i) increase the P content in the soil profile; (ii) enhance the grape production; and (iii) maintain the grape must composition. An experiment on the ‘Pinot Noir’ grape in full production was carried out over three crop seasons. The treatments were without P application (C), P on the soil surface without incorporation (SP), P incorporated at 20 cm (IP20), P incorporated at 40 cm (IP40), and twice the P dose incorporated at 40 cm (2IP40). The P concentration in leaves at flowering and veraison, P content in the soil, grape production and its components, and chemical parameters of the grape must (total soluble solids, total polyphenols, total titratable acidity, total anthocyanins, and pH) were evaluated. The P concentration in leaves did not differ among the P application modes. The application of P associated with soil mobilization, especially at 20 cm depth, increased grape production. The P application modes did not affect the values of the chemical parameters of the grape must except for the total anthocyanins, which had the highest values when the vines were subjected to 2IP40. Finally, the P application and incorporation into the soil profile was an efficient strategy for increasing the grape production in full production vineyards. Full article
(This article belongs to the Special Issue Soil Fertility, Plant Nutrition and Nutrient Management)
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<p>Average temperature (°C) and accumulated monthly precipitation (mm) in the years corresponding to the 2018/19 (<b>a</b>), 2019/20 (<b>b</b>), and 2020/21 (<b>c</b>) crop seasons; and average temperature and accumulated monthly precipitation recorded over the previous 17 years in the region where the study was carried out, Santana do Livramento, southern Brazil (<b>d</b>). The dashed lines represent the average temperature and average precipitation recorded for the entire period.</p>
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<p>P concentrations in leaves at flowering (<b>a</b>) and at <span class="html-italic">veraison</span> (<b>b</b>) evaluated over three crop seasons of ‘Pinot Noir’ grapevines subjected to P application modes to a Typic Hapludalf soil in from southern Brazil. ns = non-significant difference by Tukey’s test (<span class="html-italic">p</span> &lt; 0.05). Without P application (C), P on the soil surface without incorporation (SP), P incorporated at 20 cm (IP20), P incorporated at 40 cm (IP40), and twice P dose incorporated at 40 cm (2IP40).</p>
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<p>Grape production per plant (<b>a</b>), number of clusters (<b>b</b>), average weight of clusters (<b>c</b>) and weight of 100 berries (<b>d</b>) evaluated over three crop seasons of ‘Pinot Noir’ grapevines subjected to P application modes in a Typic Hapludalf soil from southern Brazil. Lowercase letters compare the means of the treatments (P application modes) by Tukey’s test (<span class="html-italic">p</span> &lt; 0.05). ns = non-significant difference. Without P application (C), P on the soil surface without incorporation (SP), P incorporated at 20 cm (IP20), P incorporated at 40 cm (IP40), and twice P dose incorporated at 40 cm (2IP40).</p>
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<p>Total soluble solids (<b>a</b>), total anthocyanins (<b>b</b>), total polyphenols (<b>c</b>), pH (<b>d</b>), total titratable acidity (<b>e</b>), and P concentration in the grape must (<b>f</b>) evaluated over three crop seasons of ‘Pinot Noir’ grapevines subjected to P application modes in a Typic Hapludalf soil from southern Brazil. Lowercase letters compare the means of the treatments (modes of P application) using Tukey’s test (<span class="html-italic">p</span> &lt; 0.05). ns = non-significant difference. Without P application (C), P on the soil surface without incorporation (SP), P incorporated at 20 cm (IP20), P incorporated at 40 cm (IP40), and twice P dose incorporated at 40 cm (2IP40).</p>
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<p>P content in the soil extracted by Mehlich-1 in the 0–10, 10–20 and 20–40 cm layers, in a vineyard evaluated over three crop seasons subjected to P application modes to a Typic Hapludalf soil from southern Brazil. Capital letters compare the P content between soil layers using Tukey’s test (<span class="html-italic">p</span> &lt; 0.05). ns = non-significant difference between treatments in the same soil layer. In the 2018/19 crop season, the P content in the 20–40 cm layer was not determined. Without P application (C), P on the soil surface without incorporation (SP), P incorporated at 20 cm (IP20), P incorporated at 40 cm (IP40), and twice P dose incorporated at 40 cm (2IP40).</p>
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<p>Proportion of variance explained by each source of variation for each response variable. The colors represent the source of variation (P application modes, crop seasons, blocks, residuals, and interaction between P application modes and crop seasons).</p>
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<p>Conditional inference tree showing the effect of P application modes and crop seasons on grape production (<b>a</b>): total soluble solids—TSS (<b>b</b>), total anthocyanins—TA (<b>c</b>), total titratable acidity—TTA (<b>d</b>) and pH of the grape must (<b>e</b>).</p>
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<p>Relation between principal component 1 (PC1) and principal component 2 (PC2), for P concentration in the soil and leaves, grape production and its components, grape must parameters and climatic variables evaluated over three crop seasons to P application modes in the soil. Without P application (C), P on the soil surface without incorporation (SP), P incorporated at 20 cm (IP20), P incorporated at 40 cm (IP40), and twice P dose incorporated at 40 cm (2IP40).</p>
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24 pages, 6908 KiB  
Article
LP-YOLO: A Lightweight Object Detection Network Regarding Insect Pests for Mobile Terminal Devices Based on Improved YOLOv8
by Yue Yu, Qi Zhou, Hao Wang, Ke Lv, Lijuan Zhang, Jian Li and Dongming Li
Agriculture 2024, 14(8), 1420; https://doi.org/10.3390/agriculture14081420 - 21 Aug 2024
Cited by 3 | Viewed by 1664
Abstract
To enhance agricultural productivity through the accurate detection of pests under the constrained resources of mobile devices, we introduce LP-YOLO, a bespoke lightweight object detection framework optimized for mobile-based insect pest identification. Initially, we devise lightweight components, namely LP_Unit and LP_DownSample, to serve [...] Read more.
To enhance agricultural productivity through the accurate detection of pests under the constrained resources of mobile devices, we introduce LP-YOLO, a bespoke lightweight object detection framework optimized for mobile-based insect pest identification. Initially, we devise lightweight components, namely LP_Unit and LP_DownSample, to serve as direct substitutes for the majority of modules within YOLOv8. Subsequently, we develop an innovative attention mechanism, denoted as ECSA (Efficient Channel and Spatial Attention), which is integrated into the network to forge LP-YOLO(l). Moreover, assessing the trade-offs between parameter reduction and computational efficiency, considering both the backbone and head components of the network, we use structured pruning methods for the pruning process, culminating in the creation of LP-YOLO(s). Through a comprehensive series of evaluations on the IP102 dataset, the efficacy of LP-YOLO as a lightweight object detection model is validated. By incorporating fine-tuning techniques during training, LP-YOLO(s)n demonstrates a marginal mAP decrease of only 0.8% compared to YOLOv8n. However, it achieves a significant reduction in parameter count by 70.2% and a remarkable 40.7% increase in FPS, underscoring its efficiency and performance. Full article
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<p>Material and Methods part’s flow chart.</p>
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<p>IP102 dataset distribution.</p>
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<p>Diagram of ECA.</p>
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<p>Diagram of ECSA and CBAM.</p>
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<p>Contrast between traditional convolution and depthwise separable convolution.</p>
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<p>Diagram of channel shuffle. GConv donates group convolution, which is a type of convolution that divides the input channels into groups and applies convolution operations within each group independently. This approach can reduce model complexity and improve computational efficiency, making it suitable for efficient deep learning models.</p>
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<p>Structure of LP_Unit. DWConv denotes depthwise convolution. It and the following 1 × 1 convolution together form the depthwise separable convolution.</p>
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<p>Structure of LP_DownSample. DWConv denotes depthwise convolution. It and the following 1 × 1 convolution together form the depthwise separable convolution.</p>
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<p>The overall architecture of YOLOv8n, where <span class="html-italic">n</span> = 2 means that the module is repeated twice.</p>
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<p>The overall architecture of LP-YOLOn(s)n, where <span class="html-italic">n</span> = 2 means that the module is repeated twice. Also, LP_U and LP_D refer to the LP_Unit shown in <a href="#agriculture-14-01420-f007" class="html-fig">Figure 7</a> and the LP_DownSample shown in <a href="#agriculture-14-01420-f008" class="html-fig">Figure 8</a>, respectively.</p>
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<p>The whole process of lightweight YOLOv8 to obtain LP-YOLO and network training.</p>
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<p>Decline curve of the model training loss and the change curve of the mAP of (<b>a</b>) LP-YOLO(l)n and (<b>b</b>) LP-YOLO(s)n during training on the IP102 dataset (introduced in <a href="#sec2dot1dot1-agriculture-14-01420" class="html-sec">Section 2.1.1</a>). The “results” line shows the raw values per epoch, while the “smooth” line displays a smoothed version to highlight overall trends.</p>
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<p>Pictures with labels and pictures of detection results.</p>
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<p>Examples of Prediction Failures Due to Insect and Background Similarity (<b>a</b>,<b>b</b>), Growth-Stage Morphological Changes in Phyllocnistis citrella (<b>c</b>), and Species Differences in Blister Beetles (<b>d</b>).</p>
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<p>Detection results on YOLOv8n.</p>
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<p>Detection results on LP-YOLO(s)n.</p>
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<p>Comparison of heatmaps across two images. The first row displays the original image (<b>left</b>), YOLOv8n heatmap (<b>second</b>), LP-YOLO(l)n heatmap (<b>third</b>), and LP-YOLO(s)n heatmap (<b>fourth</b>) for the first image. The second row follows the same order for the second image.</p>
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<p>Images illustrating the impact of various types of noise: (<b>a</b>) original image, (<b>b</b>) Gaussian noise with a variance of 25, (<b>c</b>) Gaussian noise with a variance of 50, (<b>d</b>) salt-and-pepper noise with salt_prob and pepper_prob set to 0.05, and (<b>e</b>) salt-and-pepper noise with salt_prob and pepper_prob set to 0.1.</p>
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<p>Insects in a social state.</p>
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<p>Individual insects at important life stages.</p>
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16 pages, 17436 KiB  
Article
Airborne Natural Total Field Broadband Electromagnetics—Configurations, Capabilities, and Advantages
by Alexander Prikhodko, Andrei Bagrianski and Petr Kuzmin
Minerals 2024, 14(7), 704; https://doi.org/10.3390/min14070704 - 11 Jul 2024
Viewed by 1254
Abstract
The airborne electromagnetic system MobileMT exploits natural fields in a broadband frequency range with offset measurements of magnetic and electric field variations. It was introduced in 2018 and has since been developed in various configurations, each tailored to meet the demands of different [...] Read more.
The airborne electromagnetic system MobileMT exploits natural fields in a broadband frequency range with offset measurements of magnetic and electric field variations. It was introduced in 2018 and has since been developed in various configurations, each tailored to meet the demands of different exploration tasks, varied terrains, and geoelectrical conditions and support time-domain data with controlled primary field sources. There are four distinct airborne systems: the original MobileMT; the lighter configuration, MobileMTm; the configuration for a drone carrier, MobileMTd; and the innovative time-domain AFMAG hybrid, TargetEM. The paper describes the technical features of each system, their differences and inherent strengths, the optimal usage conditions, and insights into their applications under different conditions across various exploration tasks. Several field case studies are provided to support the natural field electromagnetics capabilities of recovering geological structures in a wide depth range, beginning from the near surface, and address the impact of parasitic IP effects on time-domain data. Full article
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<p>MobileMT system in survey configuration. (<b>a</b>) Schematic of a base station that includes two pairs of independent grounded orthogonal electric lines in the same position. (<b>b</b>) Schematic of three orthogonal dB/dT inductive coils.</p>
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<p>Typical MobileMT data frequency windows with the frequency zone (dead band), where the natural signal strength attenuates to a small level.</p>
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<p>Airborne component of MobileMTm system.</p>
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<p>TargetEM system (<b>a</b>), with the ground E-field base station acquisition system (<b>b</b>).</p>
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<p>MobileMT system on a drone.</p>
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<p>Diagram of 1.5 skin-depth with MobileMTd additional frequencies (10–20 Hz) calculated for conductive halfspace of 1–100 ohm-m.</p>
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<p>MobileMT (and ZTEM [<a href="#B12-minerals-14-00704" class="html-bibr">12</a>]) survey line with positions of TAMT stations on a magnetic field map of the study area. The overview geological map from the Mineral Resource Map of Saskatchewan, 2008 edition (Saskatchewan Ministry of Energy and Resources). Magnetic field data and the overlapped hydrology from Canada Geoscience Data (<a href="http://gdrdap.agg.nrcan.gc.ca" target="_blank">http://gdrdap.agg.nrcan.gc.ca</a>, accessed on 6 May 2024).</p>
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<p>MobileMT apparent conductivity profiles (<b>top</b>); MobileMT resistivity section (<b>middle</b>) and ZTEM resistivity section (from [<a href="#B12-minerals-14-00704" class="html-bibr">12</a>], <b>bottom</b>) over the line crossing Kianna uranium mineralization zone.</p>
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<p>Kianna zone: <b>left</b>—resistivity section extracted from ground TAMT tipper (Zxy/Zyx/Tx/Ty) 3D model; <b>right</b>—MobileMT resistivity section.</p>
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<p>Geological section (<b>top</b>) and stratigraphic column (<b>bottom</b>) of El Domo deposit [<a href="#B18-minerals-14-00704" class="html-bibr">18</a>].</p>
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<p>MobileMT resistivity sections along survey lines crossing El Domo deposit (distance between L2371 and L2351 lines is 200 m). Grey—projection of stratabound VMS mineralization on the survey lines.</p>
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<p>MobileMT resistivity 3D voxel with the El Domo VMS mineralization position (grey).</p>
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<p>MobileMT apparent conductivity profiles in 84–13,619 Hz bandwidth (<b>top</b>) and resistivity section with overlapped normalized inversion sensitivity contours (the test survey line position is in <a href="#minerals-14-00704-f015" class="html-fig">Figure 15</a>).</p>
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<p>Cumulative distribution function of normalized inversion sensitivity along the survey line in <a href="#minerals-14-00704-f009" class="html-fig">Figure 9</a>.</p>
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<p>SW of Sudbury impact structure geology (Ontario Geological Survey).</p>
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<p>Poplar porphyry deposit: (<b>A</b>) Apparent conductivity color grid (266 Hz) with drill hole positions and MobileMT lines crossing the deposit; (<b>B</b>) Geological map and Cu grades projected to the surface (from [<a href="#B22-minerals-14-00704" class="html-bibr">22</a>]); (<b>C</b>) MobileMT resistivity sections along the lines in A, with projections of drill holes; (<b>D</b>) MobileMT apparent conductivity profiles along Line 2400.</p>
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<p>Left: TargetEM time-domain, natural field EM, and VLF data profiles recorded simultaneously along 2840 survey line; right: dB/dt color grid with overlapped anomaly contours apparent conductivity natural field at 18 kHz (white) and VLF at 19.8 kHz (black) (Western Australia).</p>
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23 pages, 4550 KiB  
Systematic Review
OxInflammatory Responses in the Wound Healing Process: A Systematic Review
by Fernanda Barbosa Lopes, Mariáurea Matias Sarandy, Rômulo Dias Novaes, Giuseppe Valacchi and Reggiani Vilela Gonçalves
Antioxidants 2024, 13(7), 823; https://doi.org/10.3390/antiox13070823 - 9 Jul 2024
Cited by 7 | Viewed by 2383
Abstract
Significant sums are spent every year to find effective treatments to control inflammation and speed up the repair of damaged skin. This study investigated the main mechanisms involved in the skin wound cure. Consequently, it offered guidance to develop new therapies to control [...] Read more.
Significant sums are spent every year to find effective treatments to control inflammation and speed up the repair of damaged skin. This study investigated the main mechanisms involved in the skin wound cure. Consequently, it offered guidance to develop new therapies to control OxInflammation and infection and decrease functional loss and cost issues. This systematic review was conducted using the PRISMA guidelines, with a structured search in the MEDLINE (PubMed), Scopus, and Web of Science databases, analyzing 23 original studies. Bias analysis and study quality were assessed using the SYRCLE tool (Prospero number is CRD262 936). Our results highlight the activation of membrane receptors (IFN-δ, TNF-α, toll-like) in phagocytes, especially macrophages, during early wound healing. The STAT1, IP3, and NF-kβ pathways are positively regulated, while Ca2+ mobilization correlates with ROS production and NLRP3 inflammasome activation. This pathway activation leads to the proteolytic cleavage of caspase-1, releasing IL-1β and IL-18, which are responsible for immune modulation and vasodilation. Mediators such as IL-1, iNOS, TNF-α, and TGF-β are released, influencing pro- and anti-inflammatory cascades, increasing ROS levels, and inducing the oxidation of lipids, proteins, and DNA. During healing, the respiratory burst depletes antioxidant defenses (SOD, CAT, GST), creating a pro-oxidative environment. The IFN-δ pathway, ROS production, and inflammatory markers establish a positive feedback loop, recruiting more polymorphonuclear cells and reinforcing the positive interaction between oxidative stress and inflammation. This process is crucial because, in the immune system, the vicious positive cycle between ROS, the oxidative environment, and, above all, the activation of the NLRP3 inflammasome inappropriately triggers hypoxia, increases ROS levels, activates pro-inflammatory cytokines and inhibits the antioxidant action and resolution of anti-inflammatory cytokines, contributing to the evolution of chronic inflammation and tissue damage. Full article
(This article belongs to the Special Issue The OxInflammation Process and Tissue Repair)
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<p>PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram. The flowchart indicates the research records obtained at all standardized stages of the search process required to develop systematic reviews and meta-analyses. Based on the PRISMA statement (<a href="http://www.prisma-statement.org" target="_blank">http://www.prisma-statement.org</a> (accessed on 3 May 2024)). * Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). ** If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools.</p>
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<p>Results of the primary and secondary outcomes of the individual studies analyzed. The colour green: increased; red: decreased; yellow: undetermined and white: not analysed, indicate the results measured between the studies. MMP: matrix metalloproteinase; MDA: malondialdehyde; TBARS: Thiobarbituric acid reactive substances; LPO: lipid peroxidation; PCN: carbonylated protein; ON: nitric oxide; 3-NT: 3-nitrotyrosine; H2O2: hydrogen peroxide; 4HNE: 4-hydroxynonenal; MPO: metalloproteinase; SOD: superoxide dismutase; CAT: catalase; GST: glutathione transferase; CuZnSOD: copper–zinc superoxide dismutase; MnSOD: manganese superoxide dismutase; IL-1: interleukin-1; IL-1β: interleukin-1-beta; IL-6: interleukin-6; IL-8: interleukin-8; NRF2: nuclear factor erythroid factor 2; HO-1: the inducible isoform of HO; IKβ: Ikappaβ kinase; NF-kβ: nuclear factor kappa β; TNF-α: Tumor Necrosis Factor receptor alpha; VEGF: vascular endothelial growth factor; ANG1 and 2: angiotensin (1–2), COX-2: cyclooxygenase-2; TGF-β: transforming growth factor beta; IL-10: interleukin-10; CRP: C-reactive protein; FIB: fibrinogen. References of the articles in the figure: Back et al., 2020 [<a href="#B42-antioxidants-13-00823" class="html-bibr">42</a>]; Dhall et al., 2016 [<a href="#B43-antioxidants-13-00823" class="html-bibr">43</a>]; Dwivedi et al., 2017 [<a href="#B44-antioxidants-13-00823" class="html-bibr">44</a>]; Ganeshkumar et al., 2012 [<a href="#B45-antioxidants-13-00823" class="html-bibr">45</a>]; Gangwar et al., 2015 [<a href="#B46-antioxidants-13-00823" class="html-bibr">46</a>]; Gautam et al., 2014 [<a href="#B47-antioxidants-13-00823" class="html-bibr">47</a>]; Jridi et al., 2017 [<a href="#B48-antioxidants-13-00823" class="html-bibr">48</a>]; Kandhare et al., 2015 [<a href="#B49-antioxidants-13-00823" class="html-bibr">49</a>]; Leu et al., 2012 [<a href="#B50-antioxidants-13-00823" class="html-bibr">50</a>]; Lim et al., 2006 [<a href="#B51-antioxidants-13-00823" class="html-bibr">51</a>]; Murthy et al., 2013 [<a href="#B52-antioxidants-13-00823" class="html-bibr">52</a>]; Nafiu &amp;Rahman, 2014 [<a href="#B53-antioxidants-13-00823" class="html-bibr">53</a>]; Park et al., 2010 [<a href="#B54-antioxidants-13-00823" class="html-bibr">54</a>]; Park et al., 2011 [<a href="#B55-antioxidants-13-00823" class="html-bibr">55</a>]; Patel et al., 2019 [<a href="#B56-antioxidants-13-00823" class="html-bibr">56</a>]; Sarandy et al., 2018 [<a href="#B57-antioxidants-13-00823" class="html-bibr">57</a>]; Schanuel et al., 2020 [<a href="#B58-antioxidants-13-00823" class="html-bibr">58</a>]; Singh et al., 2017 [<a href="#B59-antioxidants-13-00823" class="html-bibr">59</a>]; Sungkar et al., 2020 [<a href="#B60-antioxidants-13-00823" class="html-bibr">60</a>]; Yadav et al., 2017 [<a href="#B61-antioxidants-13-00823" class="html-bibr">61</a>]; Yadav et al., 2018a [<a href="#B62-antioxidants-13-00823" class="html-bibr">62</a>]; Yadav et al., 2018b [<a href="#B63-antioxidants-13-00823" class="html-bibr">63</a>]; Zhang &amp; Gould, 2013 [<a href="#B64-antioxidants-13-00823" class="html-bibr">64</a>].</p>
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<p>Overview of the interrelationship of major pathways and coexisting inflammatory mediators between oxidative stress and inflammatory process in excisional skin wound healing. *** Phenotypic plasticity of macrophages; presence of M1 (pro-inflammatory phase) and presence of M2 (anti-inflammatory phase). 4HNE: 4-hidroxinonenal; Ca<sup>2+</sup>: ion calcium; CAT: catalase; COX-2: cyclooxygenase-2; Fe<sup>+</sup>: ion iron; GST: glutathione transferase; H<sub>2</sub>O<sub>2</sub>: hydrogen peroxide; HIF-1: Hypoxia-inducible factor 1; ICAM: intercellular adhesion molecule; IFN-δ: Interferon-gamma receptor; IKK: inhibitor complex nuclear factor-κβ kinase; IKβ: IkappaB kinase; IL-1: interleukin 1; IL-6: interleukin-6; IL-10: interleukin 10; iNOS: Inducible nitric oxide synthase; IP3: IP3 signaling pathway; LPO: lipid peroxidation; MPO: metalloproteinase; NF-kβ: nuclear factor kappa β; NLRP3: inflammasome NLRP3; ON: nitric oxide; PCN: carboniled protein; PCR: C-reactive protein; ROS: reactive oxygen species; SOD: superoxide dismutase; TGF-β: transforming growth factor beta; TLR: toll-like receptor; TNF-α: Tumor Necrosis Factor receptor alpha; VECAM: vascular adhesion molecule; VEGF: vascular endothelial growth factor. Figure created on BioRender.com.</p>
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<p>Risk of bias and methodological quality indicators for all studies included in the systematic review that assessed inflammation and oxidative stress during skin wound healing.</p>
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<p>Risk of bias summary: review authors’ judgments about the risk of bias items for each included study. Green: low risk of bias; Yellow: unclear risk of bias; and Red: high risk of bias. References of the articles in the figure: References of the articles in the figure: Back et al., 2020 [<a href="#B42-antioxidants-13-00823" class="html-bibr">42</a>]; Dhall et al., 2016 [<a href="#B43-antioxidants-13-00823" class="html-bibr">43</a>]; Dwivedi et al., 2017 [<a href="#B44-antioxidants-13-00823" class="html-bibr">44</a>]; Ganeshkumar et al., 2012 [<a href="#B45-antioxidants-13-00823" class="html-bibr">45</a>]; Gangwar et al., 2015 [<a href="#B46-antioxidants-13-00823" class="html-bibr">46</a>]; Gautam et al., 2014 [<a href="#B47-antioxidants-13-00823" class="html-bibr">47</a>]; Jridi et al., 2017 [<a href="#B48-antioxidants-13-00823" class="html-bibr">48</a>]; Kandhare et al., 2015 [<a href="#B49-antioxidants-13-00823" class="html-bibr">49</a>]; Leu et al., 2012 [<a href="#B50-antioxidants-13-00823" class="html-bibr">50</a>]; Lim et al., 2006 [<a href="#B51-antioxidants-13-00823" class="html-bibr">51</a>]; Murthy et al., 2013 [<a href="#B52-antioxidants-13-00823" class="html-bibr">52</a>]; Nafiu &amp;Rahman, 2014 [<a href="#B53-antioxidants-13-00823" class="html-bibr">53</a>]; Park et al., 2010 [<a href="#B54-antioxidants-13-00823" class="html-bibr">54</a>]; Park et al., 2011 [<a href="#B55-antioxidants-13-00823" class="html-bibr">55</a>]; Patel et al., 2019 [<a href="#B56-antioxidants-13-00823" class="html-bibr">56</a>]; Sarandy et al., 2018 [<a href="#B57-antioxidants-13-00823" class="html-bibr">57</a>]; Schanuel et al., 2020 [<a href="#B58-antioxidants-13-00823" class="html-bibr">58</a>]; Singh et al., 2017 [<a href="#B59-antioxidants-13-00823" class="html-bibr">59</a>]; Sungkar et al., 2020 [<a href="#B60-antioxidants-13-00823" class="html-bibr">60</a>]; Yadav et al., 2017 [<a href="#B61-antioxidants-13-00823" class="html-bibr">61</a>]; Yadav et al., 2018a [<a href="#B62-antioxidants-13-00823" class="html-bibr">62</a>]; Yadav et al., 2018b [<a href="#B63-antioxidants-13-00823" class="html-bibr">63</a>]; Zhang &amp; Gould, 2013 [<a href="#B64-antioxidants-13-00823" class="html-bibr">64</a>].</p>
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<p>Continuous cycle and interrelating oxidative stress and inflammation, schematizing the major signaling pathways, synthesis of pro- and anti-inflammatory mediators, and antioxidant enzymes involved in the repair of excisional wounds.</p>
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<p>The clinical antioxidant and anti-inflammatory modulation of inflammatory mechanisms and the consequent reduction and control of oxidative inflammation.</p>
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13 pages, 2161 KiB  
Article
Determination of Aminoglycosides by Ion-Pair Liquid Chromatography with UV Detection: Application to Pharmaceutical Formulations and Human Serum Samples
by Eliseo Herrero-Hernández, Diego García-Gómez, Irene Ramírez Pérez, Encarnación Rodríguez-Gonzalo and José Luis Pérez Pavón
Molecules 2024, 29(13), 3210; https://doi.org/10.3390/molecules29133210 - 5 Jul 2024
Viewed by 1256
Abstract
Aminoglycosides (AGs) represent a prominent class of antibiotics widely employed for the treatment of various bacterial infections. Their widespread use has led to the emergence of antibiotic-resistant strains of bacteria, highlighting the need for analytical methods that allow the simple and reliable determination [...] Read more.
Aminoglycosides (AGs) represent a prominent class of antibiotics widely employed for the treatment of various bacterial infections. Their widespread use has led to the emergence of antibiotic-resistant strains of bacteria, highlighting the need for analytical methods that allow the simple and reliable determination of these drugs in pharmaceutical formulations and biological samples. In this study, a simple, robust and easy-to-use analytical method for the simultaneous determination of five common aminoglycosides was developed with the aim to be widely applicable in routine laboratories. With this purpose, different approaches based on liquid chromatography with direct UV spectrophotometric detection methods were investigated: on the one hand, the use of stationary phases based on hydrophilic interactions (HILIC); on the other hand, the use of reversed-phases in the presence of an ion-pairing reagent (IP-LC). The results obtained by HILIC did not allow for an effective separation of aminoglycosides suitable for subsequent spectrophotometric UV detection. However, the use of IP-LC with a C18 stationary phase and a mobile phase based on tetraborate buffer at pH 9.0 in the presence of octanesulfonate, as an ion-pair reagent, provided adequate separation for all five aminoglycosides while facilitating the use of UV spectrophotometric detection. The method thus developed, IP-LC-UV, was optimized and applied to the quality control of pharmaceutical formulations with two or more aminoglycosides. Furthermore, it is demonstrated here that this methodology is also suitable for more complex matrices, such as serum, which expands its field of application to therapeutic drug monitoring, which is crucial for aminoglycosides, with a therapeutic index ca. 50%. Full article
(This article belongs to the Section Analytical Chemistry)
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<p>Comparison of the chromatograms obtained for each aminoglycoside with two hydrophilic stationary phases: (<b>a</b>) XBridge Amide and (<b>b</b>) ZIC<sup>®</sup>-HILIC. Mobile phase consisted of a mixture of 100 mM aqueous ammonium formate and acetonitrile.</p>
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<p>IP-LC-UV chromatograms obtained from mobile phases containing borate and octanesulfonate (<b>a</b>), octanesulfonate (<b>b</b>), borate (<b>c</b>) and neither borate nor octanesulfonate (<b>d</b>).</p>
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<p>IP-LC-UV chromatograms corresponding to the analysis of two commercially available formulations: (<b>a</b>) powder for injection containing 1 g of streptomycin sulphate and (<b>b</b>) tablets containing 21 mg of Dihydrostreptomycin sulphate and 39 mg of Neomycin sulphate per tablet.</p>
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<p>IP-LC-UV chromatograms obtained after precipitation of proteins of a serum sample spiked with STR and DHS at 25 mg L<sup>−1</sup> treated with the same volume of a solution of TCA 5% (red line), MPA 10% (blue line) and an extraction buffer pH 4 (green line).</p>
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<p>IP-LC-UV chromatograms corresponding to (a) standard of STR and DHS at concentration of 12.5 mg L<sup>−1</sup> in TCA (blue line), (b) in serum sample spiked before precipitation (serum/TCA 2:1) (red line) and (c) in serum sample spiked after precipitation (serum/TCA 2:1) (green line).</p>
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<p>Structures of the aminoglycosides included in this study.</p>
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9 pages, 1130 KiB  
Article
The Impact of the Reduction in Environmental Pollution during COVID-19 Lockdown on Healthy Individuals
by Christian Romero-Mesones, Miquel de Homdedeu, David Soler-Segovia, Carlos Gómez-Ollés, David Espejo-Castellanos, Inigo Ojanguren, Berta Saez-Gimenez, María-Jesús Cruz and Xavier Munoz
Toxics 2024, 12(7), 492; https://doi.org/10.3390/toxics12070492 - 4 Jul 2024
Viewed by 1650
Abstract
The lockdown imposed to combat the COVID-19 pandemic produced a historic fall in air pollution in cities like Barcelona. This exceptional situation offered a unique context in which to examine the effects of air pollutants on human health. The present study aims to [...] Read more.
The lockdown imposed to combat the COVID-19 pandemic produced a historic fall in air pollution in cities like Barcelona. This exceptional situation offered a unique context in which to examine the effects of air pollutants on human health. The present study aims to determine and compare the oxidative stress biomarkers Th1/Th2 and inflammatory-related cytokines in healthy individuals first during lockdown and then six months after the easing of the restrictions on mobility. A prospective study of a representative sample of 58 healthy, non-smoking adults was carried out. During lockdown and six months post-easing of restrictions, blood samples were drawn to measure the percentage of eosinophils, levels of Th1/Th2 and inflammatory-related cytokines assessed by a multiplex assay (BioRad Laboratories S.A., Marnes-la-Coquette, France), and levels of 8-isoprostane, glutathione peroxidase activity, and myeloperoxidase (Cayman Chemical Co., Ann Arbor, MI, USA), to assess their value as biomarkers of oxidative stress. Six months after easing mobility restrictions, increases in the levels of 8-isoprostane (p < 0.0001), IL-1β (p = 0.0013), IL-1ra (p = 0.0110), IL-4 (p < 0.0001), IL-13 (p < 0.0001), G-CSF (p = 0.0007), and CCL3 (p < 0.0001) were recorded, along with reductions in glutathione peroxidase (p < 0.0001), IFN-γ (p = 0.0145), TNFα (p < 0.0001), IP-10 (p < 0.0001), IL-2 (p < 0.0001), IL-7 (p < 0.0001), basic FGF (p < 0.0001), CCL4 (p < 0.0001), and CCL5 (p < 0.0001). No significant differences were observed in the rest of the biomarkers analyzed. The reduction in environmental pollution during the COVID-19 lockdown significantly lowered the levels of oxidative stress, systemic inflammation, and Th2-related cytokines in healthy people. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Toxicity from Air Pollutant Exposure)
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<p>Levels of 8-isoprostane (<b>A</b>), glutathione peroxidase activity (<b>B</b>), and myeloperoxidase (<b>C</b>) in the two study periods. LAP: Low Air Pollution levels; HAP: High Air Pollution levels. Data expressed as medians (range). 8-isoprostane: LAP: 33.56 pg/mL (12.96–82.38); HAP: 46.31 pg/mL (17.74–115.2). Glutathione peroxidase: LAP: 156.4 nmol/min/mL (109.8–220.7); HAP: 121 nmol/min/mL (83.89–175). Myeloperoxidase: LAP: 87.65 ng/mL (11.1–528.1); 78.67 ng/mL (27.62–310.8).</p>
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<p>Levels of IL-4 (<b>A</b>), IL-13 (<b>B</b>), IFN-γ (<b>C</b>), IP-10 (<b>D</b>), TNF-α (<b>E</b>), and IL2 (<b>F</b>) in the two study periods. LAP: Low Air Pollution levels; HAP: High Air Pollution levels. Data expressed as median (range). IL-4: LAP: 1.575 pg/mL (0.7953–5.671); HAP: 3.283 pg/mL (1.185–7.664). IL-13: LAP: 1.068 pg/mL (0–2.403); HAP: 2.338 pg/mL (2.024–3.04). IFN-γ: LAP: 1.577 pg/mL (0–25.7); HAP: 1.197 pg/mL (0.4764–12.56). TNF-α: LAP: 272.9 pg/mL (15.75–423.2); HAP: 24.71 pg/mL (12.84–31.25). IL2: LAP: 0.4228 pg/mL (0–1.852); HAP: 0 pg/mL (0–1.364).</p>
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<p>Levels of IL1β (<b>A</b>), IL1-ra (<b>B</b>), IL-7 (<b>C</b>), G-CSF (<b>D</b>), and basic FGF (<b>E</b>) in the two study periods. LAP: Low Air Pollution levels; HAP: High Air Pollution levels. Data expressed as median (range). IL1β: LAP: 0.4767 pg/mL (0.3195–2.786); HAP: 0.6777 pg/mL (0.2531–2.51). IL-1ra: LAP: 33.85 pg/mL (0–293.4); HAP: 114.4 pg/mL (0–732.2). IL-7: 27.16 pg/mL (3.502–67.2); HAP: 5.787 pg/mL (0.5594–15.33). G-CSF: 73.2 pg/mL (15.48–868.6); HAP: 93.29 pg/mL (25.04–695.6). Basic FGF: LAP: 37.85 pg/mL (12.71–53.69); HAP: 18.85 pg/mL (11.42–36.23).</p>
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<p>Levels of CC chemokines: CCL2 (<b>A</b>), CCL3 (<b>B</b>), CCL4 (<b>C</b>), and CCL5 (<b>D</b>) in the two study periods. LAP: Low Air Pollution levels; HAP: High Air Pollution levels. Data expressed as median (range). CCL2: LAP: 25.56 pg/mL (12.51–56.98); HAP: 24.48 pg/mL (8.18–126.6). CCL3: LAP: 0.7445 pg/mL (0.3322–58.22); HAP: 3.309 pg/mL (0.8479–47.07). CCL4: LAP: 212 pg/mL (130.8–262.4); HAP: 159.1 pg/mL (112.5–192.2). CCL5: LAP: 17486 pg/mL (4976–23,509); HAP: 7473 pg/mL (3521–11,093).</p>
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